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1500 Cards in this Set
- Front
- Back
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what are prions composed of?
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abnormal forms of a host protein called prion protein (PrP)
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with what is kuru associated?
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human cannibalism
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what are the prion diseases?
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kuru
creutzfeldt-jakob disease (CJD) bovine spongiform encephalopathy (BSE/mad cow disease) variant creutzfeldt-jakob disease |
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how is variant creutzfeldt-jakob disease transmitted to humans?
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from BSE-infected cattle
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what is PrP?
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prion protein
abnormal form of host protein that composes prions normally found in neurons |
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where is PrP usually found?
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neurons
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what change occurs in PrP, causing prion diseases?
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conformational change that renders it resistant to proteases
protease-resistant PrP promotes the conversion of normal protease-sensitive PrP to the abnormal form |
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how can creutzfeldt-jakob disease be transmitted from person to person?
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iatrogenically
by surgery organ transplant blood transfusion |
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define iatrogenic
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an inadvertent adverse effect or complication resulting from medical treatment or advice, including that of psychologists, therapists, pharmacists, nurses, and dentists
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viruses
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obligate intracellular parasites
use host cellular machinery to replicate consist of a nucleic acid genome surrounded by a protein coat (capsid), and sometimes encased in a lipid membrane (envelope) |
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what inclusions are produced by cytomegalovirus?
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large eosinophilic nuclear inclusion
smaller basophilic cytoplasmic inclusions |
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what inclusions are produced by herpesviruses?
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large nuclear inclusion surrounded by a clear halo
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what is a latent infection?
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a nonreplicating form of viral infection, where the virus survives in a dormant form with the potential to be reactivated later
e.g. herpes zoster virus (chickenpox and shingles) |
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describe the latent infection with herpes zoster virus
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infects and causes chickenpox in childhood
enters dorsal root ganglia and establish latency in adult life, is periodically activated to cause shingles (not in everyone) |
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bacteria
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prokaryotes
have a cell membrane, but no membrane-bound organelles; surrounded by a wall of peptidoglycan can be extracellular, facultative intracellular, or obligate intracellular |
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how do prokaryotes differ from eukaryotes?
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both have cell membranes
eukaryotes have membrane-bound organelles, but prokaryotes do not |
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pili
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surface projections in bacteria that can adhere to host cells or extracellular matrix
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what is the difference in peptidoglycan between gram-positive and gram-negative bacteria?
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gram-positive bacteria have a thick wall of peptidoglycan surrounding the cell membrane that retains crystal-violet stain
gram-negative bacteria have thin peptidoglycan walls sandwiched between two phospholipid bilayer membranes |
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where are both staphylococcus epidermidis and propionibacterium acnes typically found to colonize?
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skin
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what bacteria causes acne?
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propionibacterium acnes
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what is the major contributor to dental plaque?
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aerobic and anaerobic bacteria in the mouth, particularly streptococcus mutans
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define microbiome
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the totality of microbes, their genetic elements (genomes), and environmental interactions in a defined environment
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give examples of obligate intracellular bacteria
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chlamydia (epithelial cells)
rickettsia (endothelial cells) replicate in membrane-bound vacuoles in specific cells identified get most/all of their energy from host cell |
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what is the most frequent infectious cause of female sterility?
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chlamydia trachomatis
causes scarring and narrowing of the fallopian tubes |
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what is the most frequent infectious cause of blindness?
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chlamydia trachomatis
causes chronic inflammation of the conjunctiva that eventually causes scarring and opacification of the cornea |
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what generic diseases are caused by rickettsiae?
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injure endothelial cells, causing a hemorrhagic vasculitis, often visible as a rash
injure CNS & cause death (rocky mountain spotted fever; epidemic typhus) |
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how are rickettsiae transmitted?
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arthropod vectors
lice (epidemic typhus) ticks (rocky mountain spotted fever; ehrlichiosis) mites (scrub typhus) |
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how are mycoplasma and ureaplasma unique among extracellular bacterial pathogens?
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do not have a cell wall
tiniest free-living organisms known (125-300nm) |
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fungi
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eukaryotes
thick chitin-containing cell walls; ergosterol-containing cell membranes |
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what is thermal dimorphism?
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ability of some fungi to change form depending on the temperature
"mold in the cold" - slender filamentous hyphae outside the body "yeast in the heat" - rounded yeast cells inside the body |
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what are the two types of spores produced by fungi?
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sexual spores
asexual spores (aka conidia) |
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what are conidia?
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asexual spores of fungi
produced on specialized fruiting bodies arising along the hyphal filament |
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what are dermatophytes?
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fungal species whose infections are confined to the superficial layers of the skin
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where is coccidioides geographically restricted to?
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southwestern united states
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where is histoplasma geographically restricted to?
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ohio river valley
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what is the effect of opportunistic fungi on immunocompromised individuals?
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give rise to life-threatening infections
characterized by tissue necrosis, hemorrhage, and vascular occlusion, with little/no inflammatory response |
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what fungus commonly infects AIDS patients?
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pneumocystis jiroveci (formerly called pneumocystis carinii)
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protozoa
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single-celled eukaryotes
major cause of disease and death in developing countries intracellular replication in variety of tissues or extracellular in the urogenital system, intestine, or blood |
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in what type of cells does Leishmania replicate?
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macrophages
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what are the most prevalent intestinal protozoans?
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entamoeba histolytica
giardia lamblia |
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what are the two forms of entamoeba histolytica?
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motile trophozoites (attach to intestinal epithelial wall and may invade)
immobile cysts (resistant to stomach acids and infectious when ingested) |
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what are the two forms of giardia lamblia?
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motile trophozoites (attach to intestinal epithelial wall and may invade)
immobile cysts (resistant to stomach acids and infectious when ingested) |
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how are blood-borne protozoans transmitted? give some examples
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insect vectors where they replicate before being passed to new human hosts
plasmodium, trypanosoma, leishmania |
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how is toxoplasma gondii acquired?
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contact with oocyst-shedding kittens
eating cyst-ridden, undercooked meat |
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helminths
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highly differentiated multicellular organisms
most alternate btwn sexual reproduction in definitive host and asexual multiplication in intermediate host or vector |
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what happens once adult helminths take up residence in humans?
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do not multiply
produce eggs or larvae that are passed out in stool |
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to what is the severity of helminth-mediated disease proportional?
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number of organisms that have infected the individual
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what are ectoparasites?
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insects (lice, bedbugs, fleas) or arachnids (mites, ticks, spiders) that attach to and live on or in the skin
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how do arthropods produce disease?
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directly (damaging human host)
indirectly (serving as vectors for transmission of infectious agents) |
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what causes pediculosis?
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lice attached to hair shafts
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what is pediculosis?
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infestation with lice
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what is scabies?
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infestation of skin with mites
mites burrow into the stratum corneum |
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what are the layers of epidermis from outside-in?
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stratum corneum
stratum lucidum (only in thick skin) stratum granulosum stratum spinosum stratum basale |
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what is the malphigian layer?
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stratum spinosum and stratum basale as a unit (both considered together)
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what can be found at the site of an arthropod bite?
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mouth parts associated with a mixed infiltrate of lymphocytes, macrophages, and eosinophils
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what is gram staining used for?
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most bacteria
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what is acid-fast stain used for?
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mycobacteria
nocardia |
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what is silver stain useful for?
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fungi
legionellae pneumocystis |
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what is periodic acid-Schiff useful for?
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fungi
amoebae |
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what is mucicarmine stain useful for?
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cryptococci (encapsulated yeast)
stains the capsule |
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what is giemsa stain useful for?
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campylobacter
leishmaniae malaria |
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what are antibody probes useful for identifying?
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all classes of microorganisms
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what are cultures useful for identifying?
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all classes of microorganisms
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what are DNA probes useful for identifying?
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all classes of microorganisms
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where are organisms usually best visualized?
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advancing edge of a lesion, particularly if there's necrosis
(not at the center) |
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what is indicated by the presence of microbe-specific IgM antibodies in the serum shortly after the onset of symptoms?
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diagnostic of infection by the specific microbe
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how can an infection be diagnosed with antibody titers?
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specific antibody titers can be measured early (acute) and 4-6 weeks (convalescent) after infection
four-fold rise in titer is usually considered diagnostic |
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what are molecular diagnostics?
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nucleic acid-based tests for detecting and quantifying various pathogens
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treatment of what types of infections is guided by nucleic acid-based measurements?
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management of HBV and HCV infections is guided by nucleic acid-based viral quantification/typing
predicts resistance to antiviral drugs |
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compare PCR testing for herpes simplex virus with cultures in herpes simplex virus encephalitis
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PCR testing has a sensitivity of 80%
culture has a sensitivity of less than 10% |
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what is the manifestation of the ebola virus?
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epidemic ebola hemorrhagic fever
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what is the manifestation of the hantaan virus?
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hemorrhagic fever with renal syndrome
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what is the manifestation of legionella pneumophila?
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legionnaires disease
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what is the manifestation of campylobacter jejuni?
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enteritis
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what is the manifestation of human t-lymphocyte virus?
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aka HTLV-1
T-cell lymphoma or leukemia HTLV-associated myelopathy |
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what is the manifestation of Staphylococcus aureus?
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toxic shock syndrome
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what are the manifestations of escherichia coli O157:H7?
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hemorrhagic colitis
hemolytic-uremic syndrome |
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what is the manifestation of borrelia burgdorferi?
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lyme disease
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what is the manifestation of HIV?
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aka human immunodeficiency virus
acquired immunodeficiency syndrome (AIDS) |
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what is the manifestation of helicobacter pylori?
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gastric ulcers
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what is the manifestation of hepatitis E?
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enterically transmitted hepatitis
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what is the manifestation of hepatitis C?
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hepatitis C
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what is the manifestation of vibrio cholerae O139?
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new epidemic cholera strain
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what is the manifestation of bartonella henselae?
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cat-scratch disease
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what is the manifestation of HHV-8?
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HHV8 = kaposi sarcoma herpes virus
kaposi sarcoma in AIDS |
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what is the manifestation of west nile virus?
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west nile fever
neuroinvasive disease |
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what is the manifestation of the SARS coronavirus?
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severe acute respiratory syndrome
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what are the CDC categories for ranking bioweapons?
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A - highest risk/most dangerous
B- intermediately dangerous C - could be engineered to be dangerous |
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describe category A bioterrorism agents
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highest risk
readily disseminated/transmitted cause high mortality w/ potential for major public health impact cause public panic and social disruption require special action for public health preparedness |
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why is smallpox a category A bioweapon?
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easily transmissable in any climate/season
30% mortality rate lack of effective antiviral therapy |
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why is smallpox easily disseminated?
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it is very stable in aerosol form
a very small dose is needed for infection |
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how is smallpox naturally spread?
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direct contact with virus in skin lesions or contaminated clothing or bedding
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what are the symptoms of smallpox infection?
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initially - high fever, headache, backache
later - rash (first on mucosa of mouth, pharynx, face, and forearms->trunk and legs) that becomes vesicular and then pustular |
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when do symptoms of smallpox infection appear?
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7-17 days after infection
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why is the population susceptible to smallpox infection if there is a vaccine?
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vaccination ended in the US in 1972
vaccination immunity has waned |
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what type of bioweapon is anthrax?
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bacillus anthracis
category A |
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what type of bioweapon is botulism?
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clostridium botulinum toxin
category A |
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what type of bioweapon is yersinia pestis?
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aka the plague
category A |
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what type of bioweapon is smallpox?
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variola major virus
category A |
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what type of bioweapon is francisella tularensis?
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causes tularemia
category A |
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what type of bioweapon are filoviruses?
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e.g. ebola and marburg viruses
cause viral hemorrhagic fevers category A |
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what type of bioweapon are arenaviruses?
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e.g. Lassa and machupo viruses
cause viral hemorrhagic fevers category A |
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what type of bioweapon is Brucella sp.?
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causes brucellosis
category B |
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what type of bioweapon is the epsilon toxin of clostridium perfringens?
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category B
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what type of bioweapon are food safety threats?
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e.g. salmonella sp., E. coli O157:H7, shigella
category B |
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what type of bioweapon is burkholderia pseudomallei?
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causes melioidosis
category B |
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what type of bioweapon is burkholderia mallei?
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causes glanders
category B |
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what type of bioweapon is chlamydia psittaci?
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causes psittacosis
category B |
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what type of bioweapon is coxiella burnetti?
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causes Q fever
category B |
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what type of bioweapon is ricin toxin?
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from ricinus communis (castor beans)
category B |
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what type of bioweapon is staphylococcal enterotoxin B?
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category B
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what type of bioweapon is rickettsia prowazekii?
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causes typhus fever
category B |
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what type of bioweapon are alphaviruses?
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e.g. venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis
cause viral encephalitis category B |
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what type of bioweapon are water safety threats?
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e.g. vibrio cholerae, cryptosporidium parvum
category B |
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what type of bioweapon is Nipah virus?
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category C
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what type of bioweapon is Hantavirus?
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category C
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describe category B bioweapons
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moderately easy to disseminate
produce moderate morbidity, but low mortality require specific diagnostic and disease surveillance many are food- or water-borne |
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describe category C bioweapons
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emerging pathogens that could be engineered for mass dissemination because of availability, ease of production and dissemination
potential for high morbidity and mortality potential for great impact on health |
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what are the first defenses against infection?
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intact skin and mucosal surfaces
physical barriers that produce antimicrobial substances |
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what factors about the skin make it a good first line of defense?
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dense, keratinized outer layer of skin
low pH (about 5.5) presence of fatty acids inhibit growth of microorganisms other than residents of normal flora |
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what potential opportunists are normal flora of the skin?
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staphylococcus epidermidis
candida albicans |
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what is infected by dermatophytes?
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stratum corneum
hair nails |
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how do Schistosoma larvae, released from freshwater snails enter the body?
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penetrate swimmers' skin by releasing collagenase, elastase, and other enzymes that dissolve the extracellular matrix
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what fungus is commonly found in burns?
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pseudomonas aeruginosa
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how are most GI pathogens transmitted?
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food or drink contaminated with fecal material
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what are the normal defenses of the GI tract?
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1) acidic gastric secretions
2) viscous mucus layer covering intestinal epithelium 3) lytic pancreatic enzymes and bile detergents 4) defensins 5) normal flora 6) secreted IgA antibodies |
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what are defensins?
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mucosal antimicrobial peptides
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where are secreted IgA antibodies made?
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plasma cells located in mucosa-associated lymphoid tissues (MALT)
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what are M cells?
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specialized epithelial cells that cover mucosa-associated lymphoid tissues with a single layer
they transport antigens to the MALT and they bind/uptake numerous gut pathogens |
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what type of viruses are inactivated by bile and digestive enzymes?
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enveloped viruses
nonenveloped viruses may be resistant to bile and digestive enzymes |
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how do staphylococcal strains cause GI disease?
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while growing on contaminated food, they release powerful enterotoxins that cause food poisoning without any bacterial multiplication in the gut
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how do V. cholerae and E. coli cause GI disease?
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multiply in mucous layer overlying gut epithelium and release exotoxins that cause the gut epithelium to secrete large volumes of fluid, resulting in watery diarrhea
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how do shigella, salmonella, and campylobacter cause GI disease?
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invade and damage intestinal mucosa and lamina propria
cause ulceration, inflammation, and hemorrhage clinically manifested as dysentery |
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how does salmonella typhi cause GI disease?
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passes from damaged mucosa, through Peyer patches and mesenteric lymph nodes, and into the blood stream
results in systemic infection |
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when does fungal infection of the GI tract occur?
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mainly in immunologically compromised people
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in what form must intestinal protozoans be to infect?
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cyst form, because cysts resist stomach acid
convert to motile trophozoites in the gut |
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how do protozoans infect the intestines?
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cysts pass through stomach (they resist stomach acid)
cysts convert to motile trophozoites in gut trophozoites attach to sugars on intestinal epithelia via surface lectins |
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what happens to Giardia lamblia when it attaches to sugars on intestinal epithelia?
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attaches to epithelial brush border and multiplies there
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what happens to cryptosporidia after it attaches to sugars on intestinal epithelia?
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taken up by enterocytes, in which they form gametes and spores
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what happens to Entamoeba histolytica after it attaches to sugars on intestinal epithelia?
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causes contact-mediated cytolysis through a channel-forming pore protein
ulcerates and invades colonic mucosa |
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when do intestinal helminths cause disease?
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present in large numbers
present in ectopic sites |
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how does Ascaris lumbricoides cause disease?
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obstructs the gut
invades and damages bile ducts |
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how do hookworms cause disease?
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cause iron deficiency anemia by chronic loss of blood sucked from intestinal villi
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how does Diphyllobothrium latum cause disease?
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depletes host of vitamin B12, giving rise to illness resembling pernicious anemia
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what is the fish tapeworm?
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Diphyllobothrium latum
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where do larvae of Trichinella spiralis preferentially encyst?
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muscle
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where do echinococcus species larvae preferentially encyst?
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liver
lung |
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on what is the distance particles travel into the respiratory system dependent?
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inversely proportional to size
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where are large particles trapped in the respiratory tract?
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mucociliary blanket that lines nose and upper respiratory tract
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what is the host defense mechanism to particles/microbes that are inhaled?
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trapped in mucus secreted by goblet cells
transported by ciliary action to the back of the throat swallowed and cleared |
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what happens to particles smaller than 5um?
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travel directly to alveoli
phagocytosed by alveolar macrophages or by neutrophils recruited to the lungs by cytokines |
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what is necessary for microorganisms that invade normal healthy respiratory tract?
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must have developed specific mechanisms to overcome the mucociliary defenses or to avoid destruction by alveolar macrophages
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what mechanisms have influenza viruses developed to infect respiratory tract defenses?
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possess hemagglutinin proteins that project from the surface of the virus and bind to sialic acid on the surface of epithelial cells
host cells are induced to engulf the virus, which enters and replicates within host cells |
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what mechanisms have influenza viruses developed to exit respiratory tract epithelial cells?
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possess neuraminidase proteins on the cell surface, which cleaves sialic acid and allows virus to release from host cell
neuraminidase also lowers viscosity of mucus and facilitates viral transit w/in respiratory tract |
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why is neuraminidase a good target for anti-influenza drugs?
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neuraminidase is a protein on the cell surface of influenza viruses that is essential for cleaving sialic acid so that the virus can leave the cell
some anti-influenza drugs are sialic acid analogues that bind and inhibit neuraminidase and prevent viral release from host cells |
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what bacteria elaborate toxins that paralyze respiratory mucosal cilia?
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Haemophilus influenzae
Bordetella pertussis |
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what is the major cause of severe respiratory infection in persons with cystic fibrosis?
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Pseudomonas aeruginosa
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what bacteria produces ciliostatic substances?
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M. pneumoniae
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how do streptococcus pneumoniae and staphylococcus species infect the respiratory tract, even though they don't have specific adherence factors?
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gain access after viral infection causes a loss of ciliated epithelium
individuals with viral respiratory infection are more susceptible to secondary bacterial superinfections |
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how is the urogenital tract mostly infected?
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most urinary tract infections invade from the exterior via the urethra
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what is the normal defense against invading microorganisms in the urinary tract?
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regular flushing with urine
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what microorganisms are usually found in urine of a healthy individual?
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a healthy person's urine is usually sterile in the bladder
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how do successful urinary tract pathogens infect?
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e.g. N. gonorrhoeae, E. coli
adhere to urinary epithelium |
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why do women have more urinary tract infections than men?
|
women have more than 10x the urinary tract infections that men have because they have a shorter urethra than men
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what is pyelonephritis?
|
an ascending urinary tract infection that has reached the pyelum or pelvis of the kidney (spread in a retrograde manner from the bladder to the kidney)
major preventable cause of renal failure |
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what is the presentation of pyelonephritis?
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fever, accelerated heart rate, painful urination, abdominal pain radiating to the back, nausea, and tenderness at the costovertebral angle on the affected side
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what is the normal defense mechanism of the vagina against microorganisms?
|
low pH resulting from catabolism of glycogen in the normal epithelium by lactobacilli
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why are lactobacilli important to women?
|
normal flora of the vagina
catabolize glycogen to make lactic acid, which lowers the pH of the vagina, and protects against invading microorganisms |
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why do women on antibiotics commonly develop vaginal infections?
|
antibiotics kill the lactobacilli in the vaginal epithelium (normal flora which create the decreased pH by making lactic acid from glycogen) and allowing other bacteria to invade
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what bacteria secrete hyaluronidase? what is the effect?
|
streptococci and staphylococci
degrades the extracellular matrix between host cells so that the bacteria can invade tissues |
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what viruses are transported free in plasma?
|
poliovirus
hepatitis B virus |
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what protozoa are transported free in the plasma?
|
African trypanosomes
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what helminths are transported free in the plasma?
|
all
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what organisms are transported by leukocytes in the blood?
|
herpesviruses
HIV mycobacteria Leishmania (protozoan) Toxoplasma (protozoan) |
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what are secondary foci?
|
infectious foci seeded by blood
can be: - single and large (solitary abscess or tuberculoma) - multiple and tiny (miliary tuberculosis or Candida microabscesses) |
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what is miliary tuberculosis?
|
a contagious bacterial (M. tuberculosis) infection that has spread from the lungs to other parts of the body through the blood or lymph system
|
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what are the manifestations of bloodstream invasion by microbes during brushing of teeth?
|
these microbes are low-virulence or non-virulent
this is common and is quickly controlled by normal host defenses |
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what are the manifestations of disseminated viremia, bacteremia, fungemia, or parasitemia?
|
fever
low blood pressure systemic signs and symptoms of sepsis can be fatal, even in previously healthy individuals |
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what are the major manifestations of schistosoma mansoni?
|
liver and intestinal damage
penetrates through the skin, but localizes in blood vessels of the portal system and mesentery |
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what are the major manifestations of schistosoma hematobium?
|
cystitis
penetrates through the skin, but localizes in the urinary bladder |
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what are the possible consequences of bacterial or mycoplamal placentitis?
|
premature delivery
stillbirth |
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what are the possible consequences of viral infections of a fetus?
|
maldevelopment of the fetus
infection in early pregnancy results in most severe disease |
|
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what are the manifestations of rubella infection during the first trimester? during the third trimester?
|
first trimester:
- congenital heart disease - mental retardation - cataracts - deafness third trimester: - little/no damage |
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when is Treponema pallidum infection most detrimental to a fetus?
|
when mother is infected late in the second trimester (this is the only time that T. pallidum infection leads to confenital syphilis), it causes severe fetal osteochondritis and periostitis that leads to multiple bony lesions
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what is the major cause of AIDS in children?
|
maternal transmission of HIV
|
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what is the fecal-oral route of transmission?
|
ingestion of stool-contaminated food or water
common mode of transmission for viruses, bacteria, protozoans, and helminths |
|
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what water-borne viruses are involved in epidemic outbreaks?
|
hepatitis A virus
hepatitis E virus poliovirus rotavirus |
|
|
how are viruses infecting the oropharynx principally transmitted?
|
through saliva
e.g. EBV, CMV, mumps viruses |
|
|
what is Phthirus pubis?
|
crabs or pubic lice
|
|
|
what are zoonotic infections?
|
transmission of microbes from animals to humans, either by:
- direct contact or consumption of animal products - indirect infection via an invertebrate vector |
|
|
what are the diseases associated with herpes simplex virus?
|
primary and recurrent herpes and neonatal herpes in both males and females
|
|
|
what are the diseases associated with hepatitis B virus?
|
hepatitis in both males and females
|
|
|
what are the diseases associated with human papillomavirus?
|
cancer of penis in some males
cervical dysplasia and cancer, as well as vulvar cancer in females condyloma acuminatum in both males and females |
|
|
what are the diseases associated with HIV?
|
AIDS in both males and females
|
|
|
what are the important viral STDs?
|
herpes simplex virus (HSV)
hepatitis B virus (HBV) human papillomavirus (HPV) human immunodeficiency virus (HIV) |
|
|
what are the important bacterial STDs?
|
Chlamydia trachomatis
Ureaplasma urealyticum Neisseria gonorrhoeae Treponema pallidum Haemophilus ducreyi Klebsiella granulomatis |
|
|
what are the diseases associated with chlamydia trachomatis?
|
urethritis, epididymitis, and proctitis in males
urethral syndrome, cervicitis, bartholinitis, salpingitis and sequelae in females lymphogranuloma venereum in both males and females |
|
|
what are the diseases associated with ureaplasma urealyticum?
|
urethritis in males
nothing in females |
|
|
what are the diseases associated with neisseria gonorrhoeae?
|
epididymitis, prostatitis, and urethral stricture in males
cervicitis, endometritis, bartholinitis, salpingitis, and sequelae (infertility, ectopic pregnancy, recurrent salpingitis) in females urethritis, proctitis, pharyngitis, disseminated gonococcal infection in both males and females |
|
|
what is proctitis?
|
an inflammation of the rectum that causes discomfort, bleeding, and occasionally, a discharge of mucus or pus
|
|
|
what are the diseases associated with Treponema pallidum?
|
syphilis in both males and females
|
|
|
what are the diseases associated with Haemophilus ducreyi?
|
chancroid in both males and females
|
|
|
what are the diseases associated with Klebsiella granulomatis?
|
granuloma inguinale (donovanosis) in both males and females
|
|
|
what are the important protozoan STDs?
|
trichomonas vaginalis
|
|
|
what are the diseases associated with trichomonas vaginalis?
|
urethritis and balanitis in males
vaginitis in females |
|
|
what is balanitis?
|
an inflammation of the foreskin and head of the penis
|
|
|
why is are Shigella species and E. histolytica considered STDs?
|
typically spread by fecal-oral route, but occasionally spread by oral-anal sex
|
|
|
what is suggested by the presence of an STI in young children?
|
strongly suggests sexual abuse
|
|
|
what are the initial sites for STIs?
|
urethra
vagina cervix rectum oral pharynx |
|
|
why are STIs so dependent on person-to-person spread?
|
the causal organisms are usually short-lived outside the host
|
|
|
what two STIs are commonly associated in the United States?
|
chlamydia and gonorrhea
infection with both bacteria is so common that the diagnosis of either should lead to treatment for both |
|
|
what is caused by perinatally acquired Chlamydia trachomatis?
|
conjunctivitis
|
|
|
what is a common effect of syphilis on pregnant women?
|
commonly causes miscarriages
|
|
|
why is diagnosis of STIs in pregnant women so critical?
|
intrauterine or neonatal STI transmission can often be prevented by treatment of mother or newborn
|
|
|
what is the effect of antiretroviral treatment on incidence of newborn HIV?
|
decreased from 25% to less than 2%
|
|
|
what STIs can be easily cured with antibiotics?
|
bacterial infections such as gonorrhea, syphilis, and chlamydia
|
|
|
what are nosocomial infections?
|
infections acquired in the hospital
|
|
|
by what generic mechanisms do microorganisms cause tissue damage?
|
- contact or enter host cells and directly cause cell death
- release toxins that kill cells at a distance, release enzymes that degrade tissue components, or damage blood vessels causing ischemic necrosis - induce host immune responses that cause additional tissue damage |
|
|
what is tropism?
|
predilection for viruses to infect certain cells and not others
|
|
|
what factors determine the tropism of a virus?
|
1) expression of host cell receptors for the virus
2) presence of cellular transcription factors that recognize viral enhancer and promoter sequences 3) anatomic barriers 4) local temperature, pH, and host defenses |
|
|
what normal cellular receptors are used by HIV to enter cells?
|
gp120 on HIV binds CD4 and either CXCR4 (on T cells) or CCR5 (on macrophages)
|
|
|
what normal cellular receptors are used by EBV to enter cells?
|
gp350 on EBV binds CR2 (aka CD21) on B cells
|
|
|
give an example of when a host protease is necessary to enable binding of a virus to host cells?
|
host protease cleaves and activates influenza virus hemagglutinin
|
|
|
to what cells is the JC virus restricted? why?
|
JC virus = John Cunningham virus (type of polyomavirus)
oligodendroglia in the CNS, because promoter and enhancer DNA sequences upstream from the viral genes are active in glial cells, but not in neurons or endothelial cells |
|
|
where do rhinoviruses infect? why?
|
upper respiratory tract
replicate optimally at the lower temperature of the upper respiratory tract |
|
|
how does the poliovirus cause direct cytopathic effects?
|
inactivates cap-binding protein, which is essential for translation of host cell mRNAs but leaves translation of poliovirus mRNAs unaffected
|
|
|
how does the herpes simplex virus cause direct cytopathic effects?
|
produces proteins that inhibit synthesis of cellular DNA and mRNA and other proteins that degrade host DNA
|
|
|
how does HIV stimulate apoptosis?
|
causes cell to produce vpr protein, which is a pro-apoptotic protein
|
|
|
what accelerates acute liver failure during hepatitis B infection?
|
CTL-mediated destruction of infected hepatocytes (the normal immune response to clear the infection)
|
|
|
what are pathogenicity islands?
|
clusters of virulence genes of bacteria
|
|
|
what determines that the strains of a bacteria are related?
|
share the same "housekeeping genes"
|
|
|
what are the mobile genetic elements that spread between bacteria and can encode virulence factors?
|
plasmids
bacteriophages (viruses that infect bacteria) |
|
|
what is quorum sensing?
|
a system of stimulus and response correlated to population density
many bacteria use quorum sensing to coordinately regulate gene expression within a large population allows unicellular organisms to acquire some of the more complex properties of multicellular organisms (different cells perform different functions) |
|
|
how does S. aureus use quorum sensing to overcome host defense?
|
coordinately regulates virulence factors by secreting autoinducer peptides
as population density increases, level of autoinducer peptide increases, stimulating toxin production within population, some bacteria produce autoinducer peptide while others produce toxins |
|
|
what is a biofilm?
|
an aggregate of microorganisms in which cells adhere to each other on a surface
community of organisms living within a viscous layer of extracellular polysaccharides that adhere to host tissues or devices (intravascular catheters and artificial joints) |
|
|
what is the significance of biofilms?
|
enhance adherence of bacteria to host tissues
increase virulence of bacteria - make them inaccessible to immune effector mechanisms - increase their resistance to antimicrobial drugs important in persistence and relapse of infections (bacterial endocarditis, artificial joint infections, respiratory infections in ppl with cystic fibrosis) |
|
|
what are adhesins?
|
bacterial surface molecules that bind to host cells or extracellular matrix
|
|
|
how does streptococcus pyogenes adhere to host tissues?
|
protein F and teichoic acid projecting from bacterial cell wall
bind to fibronectin on the surface of host cells and in the ECM |
|
|
what are pili?
|
filamentous proteins on the surface of bacteria
stalks are composed of conserved repeating subunits, but tips are composed of variable amino acids |
|
|
what determines the binding specificity of bacteria?
|
variable amino acid sequence at the tips of the pili on the surface of bacteria
|
|
|
what pilus is uniquely expressed on strains of E. coli that cause urinary tract infections?
|
specific P pilus, which binds to a gal(alpha1-4)gal moiety expressed on uroepithelial cells
|
|
|
why are the pili on N. gonorrhoeae bacteria important?
|
mediate adherence of bacteria to host cells
targets of antibody response against N. gonorrhoeae |
|
|
what important mechanism allows N. gonorrhoeae to escape the immune system (particularly the humoral arm)?
|
antigenic variation in the pili expressed on the cell surface
|
|
|
what facultative intracellular bacteria infect epithelial cells?
|
Shigella
enteroinvasive E. coli |
|
|
what facultative intracellular bacteria infect macrophages?
|
M. tuberculosis
M. leprae |
|
|
what facultative intracellular bacteria infect epithelial cells and macrophages?
|
Salmonella typhi
|
|
|
what are the advantages to bacteria of growing inside cells?
|
allows them to evade certain effector mechanisms of the immune response (antibodies)
facilitates spread of bacteria (e.g. migration of macrophages carrying M. tuberculosis) |
|
|
how does M. tuberculosis enter macrophages?
|
activates the alternative complement pathway, resulting in opsonization by C3b
CR3 on macrophages binds C3b, and causes endocytosis of the bacterium |
|
|
how do gram-negative bacteria enter epithelial cells?
|
use a complex secretion system consisting of needle-like structures projecting from the bacterial surface that bind to host cells, form pores in the host cell membrane, and then inject proteins that mediate rearrangement of the cell cytoskeleton, facilitating entry
|
|
|
how does Listeria monocytogenes spread from cell to cell?
|
directly by manipulating the cell cytoskeleton to fuse neighboring cells
allows L. monocytogenes to evade immune effector mechanisms (antibodies) |
|
|
generically, what do Shigella and E. coli do once inside a host cell?
|
inhibit host protein synthesis
replicate rapidly lyse host cell within 6 hours |
|
|
what does M. tuberculosis do once it's been phagocytosed by macrophages?
|
blocks fusion of the lysosome with the phagosome
proliferates unchecked within the macrophage |
|
|
what does L. monocytogenes do once inside host cells?
|
produces a pore-forming protein (listeriolysin O) and two phospholipases that degrade the phagosome membrane
bacteria can escape phagosome into the cytoplasm |
|
|
what virulence factors are produced by L. monocytogenes to aid in its escape from host cell phagosomes?
|
listeriolysin O (pore forming protein)
2 phospholipases (membrane degrading enzymes) |
|
|
what is a toxin?
|
any bacterial substance that contributes to illness
|
|
|
what are endotoxins?
|
components of the bacterial cell that contribute to illness
|
|
|
what are exotoxins?
|
proteins that are secreted by the bacterium that contribute to illness
|
|
|
what is bacterial endotoxin?
|
a lipopolysaccharide (LPS) that is a large component of the outer membrane of gram-negative bacteria
|
|
|
what are the components of bacterial endotoxin?
|
a long-chain fatty acid anchor (lipid A) that is connected to a core sugar chain
- very similar in all gram-negative bacteria O antigen - variable carbohydrate chain that is attached to the core sugar chain |
|
|
what is the O antigen?
|
a variable carbohydrate chain that is attached to the core sugar chain of bacterial endotoxin
used diagnostically to serotype and discriminate between different strains of bacteria |
|
|
what are the negative side effects of the immune responses triggered by LPS?
|
septic shock
disseminated intravascular coagulation (DIC) adult respiratory distress syndrome mainly occur through induction of excessive TNF, IL-1, IL-12 |
|
|
how is LPS recognized by immune cells?
|
binds to cell-surface receptor CD14, and this complex then binds to Toll-like receptor 4 (TLR4)
TLR4 is a pattern recognition receptor of the innate immune response and transmits signals that lead to the cellular response |
|
|
what are the broad categories of exotoxins?
|
enzymes
toxins that alter intracellular signaling or regulatory pathways neurotoxins superantigens |
|
|
what is the effect of proteases released by S. aureus?
|
degrade proteins that hold keratinocytes together, causing epidermis to detach from deeper skin
|
|
|
what are A-B toxins?
|
toxins produced by bacteria that alter intracellular signalling or regulatory pathways
have an active (A) subunit that has enzymatic activity have a binding (B) subunit that binds cell surface receptors and delivers the A subunit into the cytoplasm |
|
|
what are the subunits of A-B toxins?
|
A subunit = active subunit = subunit with enzymatic activity
B subunit = binding subunit = subunit that binds cell surface receptors and delivers A subunit to cytoplasm |
|
|
what bacteria produce neurotoxins?
|
Clostridium botulinum
Clostridium tetani |
|
|
what do neurotoxins do?
|
inhibit release of neurotransmitters, resulting in paralysis
A-B toxins, where A subunit interacts specifically with proteins involved in secretion of NTs at the synaptic cleft |
|
|
how do tetanus and botulism result in death?
|
respiratory failure due to paralysis of the chest and diaphragm muscles
|
|
|
what are superantigens?
|
bacterial toxins that stimulate very large numbers of T lymphocytes by binding to conserved portions of the T-cell receptor, leading to massive T-cell proliferation and cytokine release
|
|
|
what causes toxic shock syndrome?
|
aka TSS
superantigens made by S. aureus and S. pyogenes |
|
|
what type of hypersensitivity is the inflammatory reaction to M. tuberculosis?
|
it is a granulomatous inflammatory response caused by a delayed-type (type IV) hypersensitivity reaction
|
|
|
what is the function and cost of the hypersensitivity reaction to M. tuberculosis?
|
sequesters the bacilli and prevents spread, but also produces tissue damage and fibrosis
|
|
|
what are the pathologic consequences caused by the humoral immune response to S. pyogenes?
|
following infection with S. pyogenes, the antibodies produced against the streptococcal M protein can cross-react with cardiac proteins and damage the heart OR anti-streptococcal antibodies binding to antigen form immune complexes deposit in glomeruli and cause nephritis
|
|
|
what causes rheumatic heart disease?
|
antibodies against streptococcal M protein of S. pyogenes cross react with cardiac proteins and damage the heart
seen as a sequelae to S. pyogenes infection |
|
|
what causes post-streptococcal glomerulonephritis?
|
antistreptococcal antibodies that bind to streptococcal antigens and form immune complexes deposit in renal glomeruli and produce nephritis
seen as a sequelae to S. pyogenes infection |
|
|
what are the two major sequelae to S. pyogenes infection?
|
rheumatic heart disease (streptococcal M antigen antibodies cross reacting with cardiac proteins)
post-streptococcal glomerulonephritis (anti-streptococcal antibody-antigen complexes deposit in glomeruli) |
|
|
what is an important early event in the development of inflammatory bowel disease?
|
compromise of the intestinal epithelial barrier, which enables the entry of both pathogenic and commensal microbes and their interactions with local immune cells, resulting in inflammation
|
|
|
what are the evolved means of immune system evasion that have become important determinants of bacterial virulence and pathogenicity?
|
1) growth in niches that are inaccessible to the immune system
2) antigenic variation 3) resistance to innate immune defenses 4) impairment of effective T-cell antimicrobial responses by specific or nonspecific immunosuppression |
|
|
what is the advantage for microbes to propagate in the lumen of the intestine or gall bladder?
|
concealed from cell-mediated immune defenses
C. difficile in intestinal lumen S. typhi in gallbladder lumen |
|
|
how do tapeworm larvae evade immune defenses?
|
form cysts in host tissues that are covered by a dense capsule and are thus inaccessible to host immune cells and antibodies
|
|
|
how do viruses create antigenic variation?
|
low fidelity of viral RNA polymerases (HIV, influenza virus)
reassortment of viral genome (influenza virus) |
|
|
how do Trypanosoma species create antigenic variation?
|
have many genes for their major surface antigen, VSG, and can vary the expression of it
|
|
|
what is the major surface antigen of Trypanosoma species?
|
VSG
have many genes for it and can thereby vary the expression of it to create antigenic variation |
|
|
what differs between the 80 serotypes of S. pneumoniae?
|
capsular polysaccharides
|
|
|
what are the cationic antimicrobial peptides? what is their purpose?
|
defensins
cathelicidins thrombocidins provide important initial defense against invading microbes |
|
|
how is the carbohydrate capsule of pneumonia- or meningitis-causing bacteria an important viulence factor?
|
shields the bacterial antigens
prevents phagocytosis by neutrophils (e.g. pneumococcus, meningococcus, H. influenzae) |
|
|
how does E. coli cause meningitis?
|
E. coli with the K1 capsule (which contains sialic acid) cannot activate the alternative complement pathway because sialic acid will not bind C3b
these bacteria escape from complement-mediated lysis and opsonization-directed phagocytosis, and subsequently cause meningitis in newborns |
|
|
what are the effects that toxins produced by bacteria can have on phagocytes?
|
kill them
prevent their migration diminish their oxidative burst |
|
|
how has Salmonella evolved to reduce TLR activation?
|
modified the lipid moiety of LPS, such that TLR activation is reduced
|
|
|
how does S. aureus inhibit phagocytosis?
|
covered by protein A molecules that bind to the Fc portion of antibodies, preventing them from opsonizing the bacteria
|
|
|
what bacteria secrete proteases that degrade antibodies?
|
Neisseria
Haemophilus Streptococcus |
|
|
what bacteria can multiply within phagocytes?
|
mycobacteria
Listeria Legionella |
|
|
what fungi can multiply within phagocytes?
|
Cryptococcus neoformans
|
|
|
what protozoans can multiply within phagocytes?
|
leishmania
trypanosomes toxoplasmas |
|
|
what mechanisms have viruses evolved to combat secreted interferons?
|
producing soluble homologues of IFN-alpha/beta/gamma receptors that bind to and inhibit actions of secreted IFNs
producing proteins that inhibit intracellular JAK/STAT signaling downstream of IFN receptors inactivate/inhibit dsRNA-dependent protein kinase (PKR), a key mediator of antiviral effects of IFN |
|
|
what is PKR?
|
double-stranded RNA-dependent protein kinase
a key mediator of the antiviral effects of interferon |
|
|
what is the advantage conferred to viruses by blocking apoptosis in a host cell?
|
may give the viruses time to complete replication, assembly and exit, promote viral persistence, and contribute to cell transformation
|
|
|
how do herpesviruses evade T cell-mediated immunity?
|
binds to/alters localization of MHC class I proteins impairing peptide presentation to CD8+ T cells
express MHC class I homologues that act as effective inhibitors of NK cells by engaging killer inhibitory receptors target MHC class II molecules for degradation, impairing antigen presentation to CD4+ T cells |
|
|
what viruses have evolved to bind to or alter localization of MHC class I proteins?
|
DNA viruses (herpesviruses, including HSV, CMV, and EBV)
impairs peptide presentation to CD8+ T cells |
|
|
what infections are common in individuals with antibody deficiency?
|
bacterial - S. pneumoniae, H. influenzae, S. aureus
viral - rotavirus, enteroviruses |
|
|
what infections are common in individuals with T-cell defects?
|
intracellular pathogens (viruses and some parasites)
|
|
|
what infections are common in individuals with complement protein deficiencies?
|
S. pneumoniae
H. influenzae N. meningitidis |
|
|
what infections are common in individuals with deficiencies in neutrophil function?
|
S. aureus
gram-negative bacteria fungi |
|
|
what bacterial respiratory infections are common in patients with cystic fibrosis?
|
Pseudomonas aeruginosa
Staphylococcus aureus Burkholdaria cepacia |
|
|
what infections are common in individuals with sickle cell anemia? why?
|
infections with encapsulated bacteria such as Streptococcus pneumoniae
these bacteria are normally opsonized and phagocytosed by splenic macrophages, but in sickle cell patients there is a lack of splenic function |
|
|
what bacterial infection is common in patients with burns?
|
Pseudomonas aeruginosa
|
|
|
what is the effect of profound neutropenia on pyogenic bacteria?
|
though they would normally evoke a vigorous leukocyte response, they may cause rapid tissue necrosis with little leukocyte exudation in a profoundly neutropenic host
|
|
|
what is suppurative (purulent) inflammation?
|
pattern formed by reaction to acute tissue damage, characterized by increased vascular permeability and leukocytic infiltration, predominantly of neutrophils
|
|
|
what attracts neutrophils to the sites of purulent inflammation?
|
release of chemoattractants from the pyogenic bacteria that evoke the response (extracellular gram-positive cocci and gram-negative rods)
|
|
|
what is the effect of pneumococci on the lungs?
|
lobar pneumonia that spares the alveolar walls and resolves completely
|
|
|
what is the effect of staphylococci and Klebsiella on the lungs?
|
destroy alveolar walls and form abscesses that heal with scar formation
|
|
|
diffuse, predominantly mononuclear, interstitial infiltrates that develop acutely are often a response to what?
|
viruses
intracellular bacteria intracellular parasites spirochetes helminths **these are common features of all chronic inflammatory processes** |
|
|
what type of immune cells are abundant in the primary and secondary lesions of syphilis?
|
plasma cells
|
|
|
what type of cells predominate in HBV infection or viral infections of the brain?
|
lymphocytes
|
|
|
what is granulomatous inflammation?
|
a distinctive form of mononuclear inflammation usually evoked by infectious agents that resist eradication and are capable of stimulating strong T cell-mediated immunity (e.g. M. tuberculosis, Histoplasma capsulatum, schistosome eggs)
characterized by accumulation of activated macrophages called "epitheloid cells" which may fuse to form giant cells; sometimes there are central areas of caseous necrosis |
|
|
what type of organisms usually produce cytopathic-cytoproliferative reactions?
|
viruses
|
|
|
what are the characteristics of cytopathic-cytoproliferative reactions?
|
cell necrosis or cellular proliferation usually with sparse inflammatory cells
|
|
|
what viruses induce cells to fuse and form polykaryons?
|
polykaryons = fused, multinucleated cells
measles virus herpesviruses |
|
|
what is caused by focal cell damage of the skin?
|
detachment of epithelial cells, forming blisters
|
|
|
what is the appearance of tissue necrosis caused by organisms that secrete powerful toxins?
|
few inflammatory cells are present
resemble infarcts with disruption or loss of basophilic nuclear staining and preservation of cellular outlines caused by organisms such as clostridium perfringens that cause such rapid and severe necrosis that tissue damage is the dominant feature |
|
|
when do clostridia pathogens usually infect?
|
opportunistically
introduced into muscle tissue by penetrating trauma infection of the bowel in a neutropenic host |
|
|
what is caused by Entamoeba histolytica?
|
colonic ulcers and liver abscesses characterized by extensive tissue destruction with liquefactive necrosis and without a prominent inflammatory infiltrate
|
|
|
what is caused by chronic HBV infection?
|
cirrhosis of the liver, in which dense fibrous septae surround nodules of regenerating hepatocytes
|
|
|
how many serotypes are there of the mumps virus?
|
one serotype (therefore infects only once)
|
|
|
how many serotypes are there of the influenza virus?
|
multiple (can repeatedly infect the same individual because of antigenic variation)
|
|
|
what process can allow the same serotype of a virus to infect the same person repeatedly?
|
waning of immune response to some transient viruses
(e.g. respiratory syncytial virus) |
|
|
what is the leading cause of vaccine-preventable death and illness worldwide?
|
measles (rubeola) virus
|
|
|
what disease is caused by rubeola virus?
|
measles virus
|
|
|
how many people are affected by measles each year?
|
more than 20,000,000 people
|
|
|
why are children in developing countries 10-1000 times more likely to die of measles pneumonia than are children in developed countries?
|
poor nutrition
|
|
|
what caused the incidence of measles infection to decrease dramatically?
|
licensing of a measles vaccine in 1963
|
|
|
how is diagnosis of measles usually made?
|
clinical presentation
serology detection of viral antigen in nasal exudate or urinary sediment |
|
|
rubeola virus
|
aka measles virus
ssRNA virus (paramyxovirus family) only one serotype |
|
|
what viruses belong to the paramyxovirus family?
|
measles virus
mumps virus respiratory syncytial virus parainfluenza virus human metapneumovirus |
|
|
what is the major cause of lower respiratory infections in infants?
|
respiratory syncytial virus (RSV)
|
|
|
what two cell-surface receptors have been identified for the measles virus?
|
CD46 (complement regulatory protein that inactivates C3 convertases)
SLAM (molecule involved in T cell activation) |
|
|
what is CD46?
|
a complement regulatory protein that inactivates C3 convertases
expressed on all nucleated cells |
|
|
what is SLAM?
|
signaling lymphocytic activation molecule
a molecule involved in T-cell activation expressed on cells of the immune system |
|
|
what protein on measles virus is bound by CD46 and SLAM?
|
viral hemagglutinin protein
|
|
|
how is measles virus transmitted?
|
respiratory droplets
|
|
|
where does measles virus replicate?
|
initially - upper respiratory epithelial cells
later - local lymphoid tissue can replicate in epithelial cells, endothelial cells, monocytes, macrophages, dendritic cells, and lymphocytes |
|
|
what follows replication of the measles virus in lymphatic tissue?
|
viremia and systemic dissemination of the virus to many tissues (conjunctiva, respiratory tract, urinary tract, small blood vessels, lymphatic system, CNS)
|
|
|
what illnesses can be caused by measles virus?
|
croup
pneumonia diarrhea with protein-losing enteropathy keratitis with scarring and blindness encephalitis hemorrhagic rashes (black measles) |
|
|
what type of immunity controls infection with measles virus?
|
T cell-mediated immunity controls infection and produces measles
antibody-mediated immunity protects against reinfection |
|
|
what type of hypersensitivity reaction is the measles rash?
|
type IV (cell-mediated) hypersensitivity reaction to measles-infected cells in the skin
|
|
|
how does the measles virus result in secondary bacterial and viral infection?
|
causes transient, but profound, immunosuppression
|
|
|
what is the major cause of measles-related morbidity and mortality?
|
secondary bacterial and viral infections permitted by the transient, but profound, immunosuppression caused by measles virus
|
|
|
what are the alterations in innate and adaptive immunity caused by measles virus?
|
defects in dendritic cell and lymphocyte function
|
|
|
what are the rare late complications of measles?
|
subacute sclerosing panencephalitis
measles inclusion body encephalitis |
|
|
what is involved in the subacute sclerosing panencephalitis caused by the measles virus?
|
replication-defective variant of measles may be involved
|
|
|
describe the rash seen with measles infection
|
blotchy, reddish brown rash
on the face, trunk, and proximal extremities produced by dilated skin vessels, edema, and a moderate, nonspecific, mononuclear perivascular infiltrate |
|
|
what are Koplik spots?
|
ulcerated mucosal lesions in the oral cavity near the opening of Stensen ducts
marked by necrosis, neutrophilic exudate, and neovascularization seen in patients with measles infection |
|
|
what are Stensen ducts?
|
aka parotid gland
the route that saliva takes from the parotid gland into the mouth |
|
|
what is seen in the lymphoid organs of measles patients?
|
marked follicular hyperplasia, large germinal centers, and randomly distributed Warthin-Finkeldey cells
|
|
|
what are Warthin-Finkeldey cells?
|
multinucleate giant cells, which have eosinophilic nuclear and cytoplasmic inclusion bodies
these cells are pathognomic of measles infection found in the lung, sputum, and lymphoid organs |
|
|
what is a pathognomic sign?
|
a particular sign whose presence means that a particular disease is present beyond any doubt (diagnostic disease)
|
|
|
to what viral family does the mumps virus belong?
|
paramyxovirus family
|
|
|
what are the activities of of the two surface glycoproteins of the mumps virus?
|
one has hemagglutinin and neuraminidase activities
one has cell fusion and cytolytic activities |
|
|
how is the mumps virus transmitted?
|
enters upper respiratory tract via inhalation of respiratory droplets
|
|
|
how does the mumps virus infect individuals?
|
enters the URT via respiratory droplets
spreads to draining lymph nodes where they replicate in lymphocytes spread through the blood to the salivary and other glands infects salivary gland ductal epithelial cells |
|
|
what cells are infected by mumps virus?
|
activated T lymphocytes (replication)
salivary gland ductal epithelial cells |
|
|
in what type of cells does the mumps virus preferentially replicate?
|
activated T lymphocytes
|
|
|
what happens when mumps virus infects salivary gland ductal epithelial cells?
|
desquamation of involved cells, edema, inflammation that leads to classic salivary gland pain and swelling of mumps
|
|
|
to what locations does the mumps virus spread after the lymph nodes?
|
salivary gland ductal epithelial cells
CNS testis ovary pancreas |
|
|
what is the most common extrasalivary gland complication of mumps infection?
|
Aseptic meningitis
occurs in about 10% of cases |
|
|
what is aseptic meningitis?
|
a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame
many cases of aseptic meningitis represent infection with viruses or mycobacteria that cannot be detected with routine methods |
|
|
what has reduced the incidence of mumps infection by 99%?
|
MMR vaccine
live-attenuated mumps virus |
|
|
what type of vaccine is the MMR vaccine?
|
vaccine against mumps, measles, and rubella (german measles)
all three viruses in the vaccine are live-attenuated |
|
|
how is mumps infection diagnosed?
|
usually by clinical presentation
serology and viral cultures can be used for definitive diagnosis |
|
|
how often is mumps parotitis bilateral?
|
70% of cases
|
|
|
how do affected salivary glands appear in mumps parotitis?
|
cross section - enlarged, doughy consistency, moist, glistening, reddish brown
microscopically - interstitium is edematous and diffusely infiltrated by macrophages, lymphocytes, and plasma cells (compresses acini and ducts) |
|
|
what happens in mumps orchitis?
|
marked testicular swelling, caused by edema, mononuclear cell infiltration, and focal hemorrhages
parenchymal swelling may compromise the blood supply and cause areas of infarction (because testis is so tightly contained in tunica albuginea) |
|
|
what is the result of mumps orchitis?
|
sterility, caused by scars and atrophy of the testis after resolution of viral infection
|
|
|
what is the result of mumps infection in the pancreas?
|
destructive lesions that cause parenchymal and fat necrosis and neutrophil-rich inflammation
|
|
|
what is caused by mumps encephalitis?
|
perivenous demyelination
perivascular mononuclear cuffing |
|
|
what type of virus is mumps virus?
|
linear, negative-sense, ssRNA
spherical, enveloped virus |
|
|
to what genus does poliovirus belong?
|
enterovirus
|
|
|
what type of virus is poliovirus?
|
spherical, unencapsulated, positive-sense ssRNA virus
|
|
|
what are the enteroviruses?
|
(+)ssRNA viruses
includes: - coxsackie viruses - echoviruses - poliovirus - rhinovirus - enterovirus 70 |
|
|
to what virus family does poliovirus belong?
|
picornaviridae
|
|
|
what diseases are caused by coxsackie viruses?
|
coxsackievirus A:
- childhood diarrhea and rashes - viral meningitis coxsackievirus B: - myopericarditis - viral meningitis |
|
|
what disease is caused by enterovirus 70?
|
conjunctivitis
|
|
|
what diseases are caused by echovirus?
|
viral meningitis
|
|
|
what is the Salk vaccine?
|
aka Salk formalin-fixed vaccine
killed vaccine that includes all three major strains of poliovirus |
|
|
what is the Sabin vaccine?
|
aka Sabin oral vaccine
live-attenuated vaccine that includes all three major strains of poliovirus |
|
|
what factors have resulted in the virtual elimination of poliovirus?
|
infects humans but not other animals
only briefly shed doesn't undergo antigenic variations effective prevention with Salk (killed) and Sabin (live-attenuated) vaccines |
|
|
where does poliovirus persist?
|
parts of Africa
|
|
|
how is poliovirus transmitted?
|
fecal-oral route
|
|
|
what is the process of infection of poliovirus?
|
infects tissues of the oropharynx
secreted into saliva and swallowed multiplies in the intestinal mucosa and lymph nodes (transient viremia and fever) invades the CNS and replicates in motor neurons of the spinal cord or brain stem |
|
|
why does poliovirus infect only humans?
|
uses human CD155 to gain entry into cells but does not bind to cells in other species
|
|
|
what are the outcomes of poliovirus infection?
|
most are asymptomatic
spinal poliomyelitis (virus replicates in motor neurons of the spinal cord) bulbar poliomyelitis (virus replicates in motor neurons of the brain stem) |
|
|
in how many cases of poliovirus infection does the virus invade the CNS?
|
1/100 cases
|
|
|
what part of the immune system controls poliovirus infection?
|
antiviral antibodies
|
|
|
how can poliovirus spread to the CNS?
|
secondary to viremia
retrograde transport along axons of motor neurons |
|
|
what causes the rare cases of poliomyelitis that occur after vaccination?
|
mutations of the attenuated viruses to wild-type forms
|
|
|
how is poliovirus infection diagnosed?
|
viral culture of throat secretions or stool
serology |
|
|
to what viral family does West Nile virus belong?
|
flaviviridae
|
|
|
what type of virus is West Nile Virus?
|
spherical, enveloped, (+)ssRNA virus
arbovirus |
|
|
what is an arbovirus?
|
aka arthropod-borne virus
virus that is transmitted by a bite from mosquitoes, flies, sand flies, lice, fleas, ticks and mites most are spherical; all but African swine fever virus have RNA genomes |
|
|
what is the geographic distribution of West Nile virus?
|
broad distribution in the old world
outbreaks in Africa, Middle East, Europe, Southeast Asia, and Australia |
|
|
when was West Nile Virus first detected in the US?
|
1999 during an outbreak in New York City
|
|
|
what is the major reservoir for West Nile Virus?
|
wild birds
(develop prolonged viremia, and humans are usually incidental hosts) |
|
|
aside from mosquitoes, how has West Nile Virus been documented to be transmitted?
|
blood transfusion
transplanted organs breast milk transplacentally |
|
|
where does West Nile virus replicate after inoculation by a mosquito?
|
replicates in skin dendritic cells, which migrate to lymph nodes
virus replicates further, enters the bloodstream, and crosses the blood-brain barrier (in some individuals) infects neurons |
|
|
what is the importance of CCR5 in West Nile virus infection?
|
essential host factor to resist neuroinvasive infection
|
|
|
what is the CCR5delta32 allele?
|
a mutated allele for the chemokine receptor CCR5
contains a 32-base pair deletion in the coding sequence for the CCR5 receptor in homozygous individuals, it results in a complete loss of function it is associated with symptomatic and lethal West Nile virus infection, as well as immunity against HIV infection |
|
|
what are the outcomes of West Nile virus infection?
|
usually asymptomatic
mild, short-lived febrile illness associated with headache and myalgia (20% of cases) maculopapular rash in approximately 1/2 of cases |
|
|
what are the CNS complications of West Nile virus?
|
meningitis
encephalitis meningoencephalitis not frequent (1/150 clinically apparent infections) |
|
|
what is the mortality in West Nile infections with meningoencephalitis?
|
10% mortality
long-term cognitive and neurologic impairment in many survivors |
|
|
what characteristics have been noted in the brains of patients who died of West Nile virus?
|
perivascular and leptomeningeal chronic inflammation
microglial nodules neuronophagia (predominantly involves the temporal lobes and brain stem) |
|
|
who is at greatest risk for infection with West Nile virus?
|
immunosuppressed individuals
elderly |
|
|
what are the rare complications of West Nile virus?
|
hepatitis
myocarditis pancreatitis |
|
|
how is West Nile virus infection diagnosed?
|
usually by serology
viral culture and PCR-based tests are also used |
|
|
what are the four viral families that cause viral hemorrhagic fevers?
|
arenaviruses
filoviruses bunyaviruses flaviviruses |
|
|
what are viral hemorrhagic fevers?
|
systemic infections, caused by enveloped RNA viruses in four families (arenaviruses, filoviruses, bunyaviruses, flaviviruses)
characterized by fever and bleeding disorders and all can progress to high fever, shock and death in extreme cases |
|
|
what type of transmission is required for the viruses that cause viral hemorrhagic fevers?
|
depend on animal or insect host for survival and transmission
|
|
|
what restricts the geographic range of viral hemorrhagic fever viruses?
|
they are restricted to areas in which their hosts reside
|
|
|
how are humans infected with viral hemorrhagic fever viruses?
|
come into contact with infected hosts or insect vectors
some (ebola, marburg, lassa) can spread from person to person |
|
|
what is the spectrum of illnesses caused by viral hemorrhagic fever viruses?
|
relatively mild acute disease, characterized by fever, headache, myalgia, rash, neutropenia, and thrombocytopenia
severe, life-threatening disease - sudden hemodynamic deterioration, shock |
|
|
why are viral hemorrhagic fever viruses potential biologic weapons?
|
infectious properties
morbidity and mortality absence of therapy and vaccines |
|
|
what causes the hemorrhagic manifestations in viral hemorrhagic fevers?
|
thrombocytopenia
severe platelet dysfunction endothelial dysfunction |
|
|
what is seen in the liver of a patient with a viral hemorrhagic fever?
|
necrosis and hemorrhage
|
|
|
where do viruses that cause viral hemorrhagic fever replicate?
|
endothelial cells
direct cytopathic effects may contribute to disease, but most manifestations are related to activation of innate immune responses |
|
|
what is caused by viral infection of macrophages and dendritic cells?
|
release of mediators that modify vascular function and have procoagulant activity
|
|
|
what type of virus are herpesviruses?
|
large encapsulated viruses with dsDNA genome
|
|
|
what is latency?
|
inability to recover infectious particles from cells that harbor the virus
|
|
|
what are the three subgroups of herpesviruses?
|
alpha-group (HSV-1, HSV-2, VZV) - infect epithelial cells; latent infections in neurons
lymphotropic beta-group (CMV, HHV-6, HHV-7) - infect and produce latent infection in a variety of cell types gamma-group viruses (EBV, HHV-8) - latent infection in lymphoid cells |
|
|
what disease is caused by HHV-6?
|
aka human herpesvirus-6
causes exanthem subitum (aka roseola infantum, aka sixth disease) benign rash of infants |
|
|
what disease is caused by HHV-7?
|
aka human herpesvirus-7
doesn't have a known disease association |
|
|
what are the eight types of herpesviruses?
|
HSV-1
HSV-2 HHV-3 (VZV) HHV-4 (EBV) HHV-5 (CMV) HHV-6 HHV-7 HHV-8 (KSHV) |
|
|
what is herpesvirus simiae?
|
Old World monkey virus that resembles HSV-1 and can cause fatal neurologic disease in animal handlers, usually resulting from an animal bite
|
|
|
where do HSV-1 and HSV-2 replicate?
|
in the skin and mucous membranes at the site of entrance (usually oropharynx or genitals)
spread to sensory neurons that innervate the primary sites of replication |
|
|
what is caused by HSV-1 and HSV-2 infection of epithelia?
|
vesicular lesions of the epidermis
|
|
|
how are HSV-1 and HSV-2 spread to sensory neurons?
|
viral nucleocapsids are transported along axons to the neuronal cell bodies of sensory neurons
establish latent infection in cell body |
|
|
what nucleic acids remain in the viral nucleus of latent HSV-1 and HSV-2 infections?
|
viral DNA remains in the nucleus
only latency-associated viral RNA transcripts (LATs) are synthesized |
|
|
what viral proteins are produced in latent HSV infections?
|
none
only latency-associated viral RNA transcripts (LATs) are synthesized LATs may be miRNAs that confer resistance to apoptosis and thus contribute to virus persistence in sensory neurons |
|
|
how do HSVs evade antiviral CTLs? how do they evade the humoral immune defenses?
|
antiviral CTLs - inhibit the MHC class I recognition pathway
humoral - produce receptors for the Fc domain of immunoglobulin; produce inhibitors of complement |
|
|
what is the major infectious cause of corneal blindness in the United States?
|
HSV-1
corneal epithelial disease is thought to be due to direct viral damage corneal stromal disease is immune mediated |
|
|
what is the major cause of fatal sporadic encephalitis in the United States?
|
HSV-1
occurs when the virus spreads to the brain, particularly the temporal lobes and orbital gyri of the frontal lobes |
|
|
what individuals are particularly at risk for disseminated herpesvirus infections?
|
nonates
individuals with compromised cellular immunity |
|
|
what are Cowdry type A inclusion bodies?
|
pink to purple, eosinophilic, intranuclear inclusions that consist of intact and disrupted virions with the stained host cell chromatin pushed to the edges of the nucleus
seen in HSV, CMV, and VZV herpesvirus infections |
|
|
where are the fever blisters (cold sores) found in HSV-infected patients?
|
facial skin around mucosal orifices (lips, nose)
distribution is frequently bilateral and independent of dermatomes |
|
|
what causes intraepithelial vesicles (blisters) in HSV-infected patients?
|
intracellular edema and ballooning degeneration of epidermal cells
they frequently burst and crust over, but some result in superficial ulcerations |
|
|
what is gingivostomatitis?
|
vesicular eruption extending from the tongue to the retropharynx, which causes cervical lymphadenopathy
caused by HSV-1 infection, usually seen in children |
|
|
what is herpetic whitlow?
|
a lesion (whitlow) on a finger or thumb caused by the herpes simplex virus (HSV-1 or HSV-2)
it is a painful infection that typically affects the fingers or thumbs occurs in infants (sucking thumb with primary oral HSV-1 infection) and in health care workers (dental and medical; in contact with oral secretions) |
|
|
what virus causes genital herpes?
|
more often by HSV-2 than HSV-1 (though, with more oral sex, there is an increase in overlap between the territories of HSV-1 and HSV-2)
|
|
|
how does genital herpes present?
|
vesicles on the genital mucous membranes as well as on the external genitalia that are rapidly converted into superficial ulcerations, rimmed by inflammatory infiltrate
|
|
|
how is congenital herpes transmitted?
|
transmitted to neonates during passage through the birth canal of infected mothers
|
|
|
how does congenital herpes (HSV-2) infection present in neonates?
|
may be mild
more commonly - fulminating with generalized lymphadenopathy, splenomegaly, and necrotic foci throughout the lungs, liver, adrenals, and CNS |
|
|
where are the necrotic foci in fulminating congenital herpes infections?
|
lungs
liver adrenals CNS |
|
|
what are the two forms of corneal lesions caused by HSV?
|
herpes epithelial keratitis - typical virus-induced cytolysis of the superficial epithelium
herpes stromal keratitis - infiltrates of mononuclear cells around keratinocytes and endothelial cells (causes neovascularization, scarring, opacification of the cornea, and eventual blindness) |
|
|
what is kaposi varicelliform eruption?
|
rare but severe disseminated herpes (HSV-1 or HSV-2) infection that generally occurs at sites of skin damage produced by, for example, atopic dermatitis, burns, or eczema
|
|
|
what is eczema herpeticum?
|
rare but severe disseminated herpes (HSV-1 or HSV-2) infection that generally occurs at sites of skin damage produced by, for example, atopic dermatitis, burns, or eczema
|
|
|
how does kaposi varicelliform eruption differ from eczema herpeticum?
|
kaposi - generalized vesiculating involvement of the skin
eczema - confluent, pustular, or hemorrhagic blisters, often with bacterial superinfection and viral dissemination to internal viscera |
|
|
what is the frequent complication of herpes esophagitis?
|
superinfection with bacteria or fungi
|
|
|
how is herpes bronchopneumonia introduced?
|
intubation of a patient with active oral lesions
it is often necrotizing |
|
|
what can be caused by herpes hepatitis?
|
liver failure
|
|
|
what two conditions are caused by varicella zoster virus?
|
aka VZV
chickenpox (acute infection) shingles (reactivation of latent infection) |
|
|
when is chickenpox most severe?
|
it is mild in children, but more severe in adults and in immunocompromised individuals
|
|
|
where does VZV infect?
|
mucous membranes, skin, neurons
causes a self-limited primary infection in immunocompetent individuals evades immune responses and establishes a latent infection in sensory ganglia |
|
|
how is VZV transmitted?
|
transmitted in epidemic fashion by aerosols
disseminates hematogenously causes widespread vesicular skin lesions |
|
|
define hematogenous
|
involving, spread by, or arising in the blood
|
|
|
what cells does VZV infect?
|
neurons and/or satellite cells around neurons in the dorsal root ganglia
may recur many years after the primary infection, causing shingles |
|
|
where is the most frequent and most painful localized recurrence of VZV?
|
dermatomes innervated by the trigeminal ganglia
|
|
|
how is VZV infection diagnosed?
|
viral culture
detection of viral antigens in cells scraped from superficial lesions |
|
|
how long after respiratory infection does a chickenpox rash occur?
|
approximately 2 weeks
|
|
|
how do the lesions of a chickenpox rash present?
|
appear in multiple waves centrifugally from the torso to the head and extremities
each lesion progresses rapidly from a macule to a vesicle (resembling a dewdrop on a rose petal) after a few days, most vesicles rupture, crust over, and heal by regeneration, leaving no scars |
|
|
how do chickenpox vesicles appear on histologic examination?
|
contain intranuclear inclusions in epithelial cells
|
|
|
what causes scarring in chickenpox?
|
bacterial superinfection of vesicles that are ruptured by trauma
leads to destruction of the basal epidermal layer and residual scarring |
|
|
how does shingles occur?
|
VZV infects acutely, causing chickenpox
it then lies dormant in the dorsal root ganglia, and after a long latent period, it is reactivated and infects sensory nerves that carry it to one or more dermatomes |
|
|
how does shingles present?
|
infects keratinocytes and causes vesicular lesions
associated with intense itching, burning, or sharp pain because of simultaneous radiculoneuritis |
|
|
when is the pain associated with shingles most severe?
|
when the trigeminal nerves are involved
|
|
|
what is Ramsay Hunt syndrome (specifically type II)?
|
disorder that is caused by the reactivation of pre-existing herpes zoster virus in a nerve cell bundle in the head (the geniculate ganglion)
neurons in this ganglion are responsible for the movements of facial muscles, the touch sensation of a part of ear and ear canal, the taste function of the frontal two-thirds of the tongue, and the moisturization of the eyes and the mouth syndrome specifically refers to the combination of this entity with weakness of the muscles activated by the facial nerve |
|
|
describe the VZV-infected sensory ganglia that has reactivated VZV in them
|
dense, predominantly mononuclear infiltrate, with herpetic intranuclear inclusions within neurons and their supporting cells
|
|
|
what disorders are caused by VZV infection?
|
chickenpox
shingles interstitial pneumonia* encephalitis* transverse myelitis* necrotizing visceral lesions* *= particularly in immunosuppressed individuals |
|
|
what type of virus is cytomegalovirus?
|
aka CMV
beta-group herpesvirus large double-stranded, linear DNA genome, encased within an icosahedral capsid, that is enveloped |
|
|
to what family does cytomegalovirus belong?
|
herpesviridae
|
|
|
what cells are latently infected by CMV?
|
monocytes and their bone marrow progenitors
|
|
|
when is CMV reactivation common?
|
when cellular immunity is depressed
|
|
|
what are the disorders caused by CMV infection?
|
asymptomatic or mononucleosis-like infection in healthy individuals
devastating systemic infections in neonates and in immunocompromised people |
|
|
how do CMV-infected cells appear on microscopic examination?
|
enlarged cell
enlarged nucleus large nuclear inclusion surrounded by a clear halo (owl's eye) |
|
|
in what disease does one see "owl's eye" inclusions microscopically?
|
CMV infection
"owl's eye" inclusions are large nuclear inclusions surrounded by a clear halo |
|
|
how is CMV transmitted?
|
transplacental transmission
cervical secretions vaginal secretions breast milk saliva venereal route respiratory secretions fecal-oral route iatrogenic transmission |
|
|
how is CMV transmitted to neonates?
|
transplacentally
cervical or vaginal secretions at birth breast milk after birth |
|
|
how is CMV transmitted to toddlers during preschool years, especially in day care centers?
|
saliva
|
|
|
what is the dominant mode of CMV transmission after 15 years of age?
|
venereal spread (sexual transmission)
also spread by respiratory secretions and fecal-oral route |
|
|
what is the most severe side effect of acute CMV infection?
|
transient, but severe immunosuppression
|
|
|
what cells are infected by CMV?
|
dendritic cells
impairs their maturation and ability to stimulate T cells |
|
|
how do herpesviruses elude immune responses?
|
downmodulate MHC class I and class II molecules
produce homologues of TNF receptor, IL-10, and MHC class I molecules |
|
|
what cells are affected by CMV infection in the glandular organs? the brain? the lungs? the kidneys?
|
glandular organs - parenchymal epithelial cells
brain - neurons lungs - alveolar macrophages, epithelial cells, endothelial cells kidneys - tubular epithelial cells, glomerular endothelial cells |
|
|
what is caused by disseminated CMV?
|
focal necrosis with minimal inflammation in virtually any organ
|
|
|
what is the result of congenital CMV infection in 95% of cases?
|
asymptomatic disease
|
|
|
what is cytomegalic inclusion disease?
|
congenital CMV infection from a mother without protective antibodies
resembles erythroblastosis fetalis |
|
|
how does cytomegalic inclusion disease present?
|
- intrauterine growth retardation
- jaundice - hepatosplenomegaly - anemia - thrombocytopenia (and subsequent bleeding) - encephalitis - microcephaly |
|
|
what is microcephaly?
|
smaller than normal brain
|
|
|
how is diagnosis of neonatal CMV made?
|
shell-virus culture of urine or oral secretions
|
|
|
what is found in infants who survive congenital CMV infection?
|
usually permanent deficits, including mental retardation, hearing loss, and other neurologic impairments
not always devastating: - interstitial pneumonitis - hepatitis - hematologic disorder |
|
|
what is the result of CMV infection acquired by passage through the birth canal or from breast milk?
|
asymptomatic in vast majority of cases
may develop interstitial pneumonitis, failure to thrive, skin rash, or hepatitis **acquire maternal antibodies against CMV so the disease is less severe** |
|
|
what is the most common clinical manifestation of CMV infection in immunocompetent hosts beyond the neonatal period?
|
infectious mononucleosis-like illness, with fever, atypical lymphocytosis, lymphadenopathy, and hepatomegaly accompanied by abnormal liver function test results, suggesting mild hepatitis
most ppl recover without sequelae, although excretion of the virus may occur in body fluids for months to years |
|
|
where does CMV remain latent?
|
leukocytes
|
|
|
what patients are susceptible to severe CMV infection?
|
immunocompromised individuals (e.g. transplant recipients, HIV-infected individuals)
|
|
|
what is the most common opportunistic viral pathogen in AIDS patients?
|
cytomegalovirus (CMV)
|
|
|
what organs are affected by serious, life-threatening disseminated CMV infections?
|
lungs (pneumonitis)
GI tract (colitis) |
|
|
what happens in pulmonary infection with CMV?
|
interstitial mononuclear infiltrate with foci of necrosis develops, accompanied by the typical enlarged cells with inclusions
can progress to full-blown acute respiratory distress syndrome |
|
|
what happens in GI infection with CMV?
|
intestinal necrosis and ulceration can develop and be extensive, leading to the formation of pseudomembranes and debilitating diarrhea
|
|
|
how is CMV infection diagnosed?
|
demonstration of characteristic morphologic alterations in tissue sections
viral culture rising antiviral antibody titer detection of CMV antigens PCR-based detection of CMV DNA |
|
|
what allows viruses like HIV and HBV to escape control by the immune system?
|
high mutation rate
|
|
|
what is caused by HBV?
|
aka hepatitis B virus
acute hepatitis chronic hepatitis |
|
|
to what viral family does HBV belong?
|
hepadnaviridae
|
|
|
what type of virus is HBV?
|
hepadnavirus
enveloped DNA virus with icosahedral nucleocapsid |
|
|
what DNA virus uses a reverse transcriptase?
|
hepatitis B virus (HBV)
|
|
|
how is HBV transmitted?
|
percutaneously (IV drug use or blood transfusion)
perinatally sexually |
|
|
what cells does HBV infect? what causes cellular injury in HBV infection?
|
hepatocytes
cellular injury occurs mainly from the immune response to infected liver cells (not cytopathic effects of the virus) |
|
|
what is the major determinant of whether a person clears HBV or becomes a chronic carrier?
|
efficacy of cytotoxic T-lymphocyte response
|
|
|
how is HBV eliminated in a patient?
|
CTLs destroy infected hepatocytes, which clears the virus as well
|
|
|
how does HBV become an established chronic infection?
|
the rate of hepatocyte infection outpaces the ability of CTLs to eliminate infected cells
happens in about 5% of adults and 90% of children infected perinatally |
|
|
what happens to the liver in chronic hepatitis B infection?
|
develops a chronic hepatitis, with lymphocytic inflammation, apoptotic hepatocytes resulting from CTL-mediated killing, and progressive destruction of liver parenchyma
long term viral replication and recurrent immune-mediated liver injury can lead to cirrhosis and increased risk for hepatocellular carcinoma |
|
|
how can an individual infected with HBV develop a "carrier state", without progressive liver damage?
|
hepatocytes are infected but the CTL response is dormant, so there is no cell-mediated damage of liver parenchyma
|
|
|
what viruses have been implicated in the causation of human cancer?
|
epstein barr virus (EBV)
human papillomavirus (HPV) hepatitis B virus (HBV) human t lymphocyte virus (HTLV-1) |
|
|
what causes infectious mononucleosis?
|
epstein barr virus (EBV)
|
|
|
what is infectious mononucleosis?
|
benign, self-limited lymphoproliferative disorder, caused by EBV
characterized by fever, generalized lymphadenopathy, splenomegaly, sore throat, and appearance in blood of mononucleosis cells |
|
|
with what neoplasms is EBV most notably associated?
|
B cell lymphomas
nasopharyngeal carcinoma |
|
|
what are the dangerous outcomes of EBV infection?
|
hepatitis
meningoencephalitis pneumonitis |
|
|
when does infectious mononucleosis typically present?
|
late adolescents or young adults among upper socioeconomic classes in developed nations
childhood in undeveloped nations |
|
|
how is EBV transmitted?
|
close human contact, frequently with the saliva during kissing
|
|
|
what is the cellular receptor for EBV?
|
an EBV envelope glycoprotein binds to CD21 (CR2), the receptor for C3d component of complement, present on B cells
|
|
|
where does EBV infection begin?
|
nasopharyngeal and oropharyngeal lymphoid tissues, particularly the tonsils
|
|
|
how does EBV gain access to submucosal lymphoid tissue?
|
transient infection of epithelium
OR transcytosis into the submucosa |
|
|
what is the process of EBV infection?
|
transmitted by saliva during kissing
infection begins in nasopharyngeal and oropharyngeal lymphoid tissues, particularly tonsils EBV gains access to submucosal lymphoid tissues (via transient epithelial infection or transcytosis) B cells are infected |
|
|
what are the two types of B cell infection caused by EBV?
|
in a minority of cells, there is productive infection with lysis of infected cells and release of virions, which may infect other B cells
in most B cells, there is a latent infection |
|
|
what is the main reservoir for latent EBV infection?
|
B cells
patients with X-linked agammaglobulinemia, who do not have B cells, do not develop latent EBV infection |
|
|
what gene products are produced during latent infection with EBV?
|
EBNA1 - binds EBV genome to chromosomes, mediating episomal persistence and maintenance
EBNA2 & LMP1 - drive B cell activation and proliferation |
|
|
what is EBNA1?
|
gene product of latent EBV infection that binds the EBV genome to chromosomes, mediating episomal persistence and maintenance
|
|
|
what is EBNA2?
|
gene product of latent EBV infection that works with LMP1 to drive B-cell activation and proliferation
stimulates transcription of many host cell genes, including genes that drive cell cycle entry |
|
|
what is LMP1?
|
latent membrane protein 1
works with EBNA2 to drive B-cell activation and proliferation acts by binding to TNF receptor-associated factors, and activates signaling pathways that mimic B-cell activation by CD40, involved in normal B-cell responses |
|
|
what happens to activated B cells in EBV infection?
|
disseminate in the circulation and secrete antibodies with several specificities, including heterophile anti-sheep red blood cell antibodies used for diagnosis of infectious mononucleosis
|
|
|
what are heterophile antibodies?
|
antibodies that bind to antigens that differ from the antigens that induced them
ex. people with mononucleosis make antibodies that agglutinate sheep or horse red blood cells in the laboratory, but these antibodies do not react with EBV |
|
|
what is the heterophile antibody test? for what is it specific?
|
test for heterophile anti-sheep red blood cell antibodies
used for diagnosis of infectious mononucleosis (EBV infection) |
|
|
when do the symptoms of infectious mononucleosis appear?
|
upon initiation of the host immune response
|
|
|
what is the most important component of the host immune response to EBV?
|
cellular immunity mediated by CD8+ cytotoxic T cells and NK cells
|
|
|
what are the atypical lymphocytes seen in the blood that are characteristic of infectious mononucleosis?
|
EBV-specific CD8+ CTLs
include CD16+ NK cells large, with abundant cytoplasm containing multiple clear vacuolations, an oval, indented, or folded nucleus, and scattered cytoplasmic azurophilic granules |
|
|
what accounts for the lymphadenopathy and splenomegaly in infectious mononucleosis?
|
reactive proliferation of T cells largely centered in lymphoid tissues
|
|
|
what are the antibodies produced in Epstein Barr virus infection?
|
early in infection - IgM antibodies against viral capsid antigens
later in infection - IgG antibodies that persist for life |
|
|
what is responsible for acting as the brakes on viral shedding in otherwise healthy individuals?
|
fully developed humoral and cellular responses to EBV
eliminates B cells expressing the full complement of EBV latency-associated genes |
|
|
what type of virus is is responsible for Burkitt lymphoma?
|
EBV
chromosomal translocation (most commonly an 8:14 translocation) involving the c-myc oncogene |
|
|
what is the result of EBV infection on lymph nodes?
|
enlarged throughout the body, principally in the posterior cervical, axillary, and groin regions
most striking histologic feature is expansion of paracortical areas by activated T cells follicles (B cell areas) are also hyperplastic but usually mild compared to paracortical areas |
|
|
what are Reed-Sternberg cells?
|
malignant cells of Hodgkin lymphoma
|
|
|
in what disease do B cells resemble Reed-Sternberg cells?
|
EBV
**the B cells infected by EBV are the cells that resemble Reed-Sternberg cells** |
|
|
what is the result of EBV infection on the spleen?
|
enlarged in most cases
usually soft and fleshy with a hyperemic cut surface especially vulnerable to rupture (rapid increase in size produces a tense, fragile splenic capsule) histologic changes = expansion in white pulp follicles and in red pulp sinusoids due to presence of numerous activated T cells |
|
|
what is the result of EBV infection on the liver?
|
at most moderate hepatomegaly
histologic features = atypical lymphocytes in portal areas and sinusoids scattered, isolated cells or foci of parenchymal necrosis may be present **similar to other forms of viral hepatitis** |
|
|
what are the atypical presentations of infectious mononucleosis?
|
malaise, fatigue, and lymphadenopathy
fever with unknown origin without significant lymphadenopathy or other localized findings hepatitis resembling one of hepatotropic viral syndromes febrile rash resembling rubella |
|
|
in increasing order of specificity, on what does the diagnosis of infectious mononucleosis (EBM infection) depend?
|
1) lymphocytosis with characteristic atypical lymphocytes
2) positive heterophile antibody reaction (monospot test) 3) specific antibodies for EBV antigens (capsid antigens, early antigens or EBV nuclear antigen) |
|
|
what is a monospot test?
|
aka heterophile antibody test
test to diagnose infectious mononucleosis (EBV infection) |
|
|
how long does infectious mononucleosis last?
|
4-6 weeks
(fatigue may last longer) |
|
|
what is the most common complication of infectious mononucleosis?
|
hepatic dysfunction with jaundice, elevated hepatic enzyme levels, disturbed appetite, and rarely even liver failure
|
|
|
what is X-linked lymphoproliferation syndrome?
|
aka Duncan disease
disorder caused by a defect in SH2D1A gene, which is primarily expressed in CTLs and NK cells SH2D1A (SAP) participates in a signaling pathway critical for an effective cellular response to EBV-infected B cells patients are often normal until they are acutely infected with EBV, often during adolescence, when the failure to control EBV infection variously leads to chronic infectious mononucleosis, agammaglobulinemia, and B-cell lymphoma |
|
|
what type of bacteria are Staphylococcus species?
|
pyogenic gram-positive cocci that form clusters like bunches of grapes
|
|
|
what bacteria form clusters that look like bunches of grapes?
|
Staphylococcus sp.
|
|
|
what conditions are caused by infection with Staphylococcus sp.?
|
skin lesions (boils, carbuncles, impetigo, scalded-skin syndrome)
abscesses sepsis osteomyelitis pneumonia endocarditis food poisoning toxic shock syndrome |
|
|
what types of infections are commonly caused by Staphylococcus epidermidis?
|
opportunistic infections in catheterized patients, patients with prosthetic heart valves, and drug addicts
|
|
|
what types of infections are commonly caused by Staphylococcus saprophyticus?
|
common cause of UTIs in young women
|
|
|
what is clumping factor?
|
surface receptor on S. aureus that binds to fibrinogen
|
|
|
how does S. aureus build a bridge to bind to host endothelial cells?
|
expresses surface receptors for fibrinogen, fibronectin, and vitronectin, using these molecules as the bridge
|
|
|
how does S. epidermidis infect prosthetic valves and catheters?
|
it has a polysaccharide capsule that allows it to attach to the artificial materials and to resist host cell phagocytosis
|
|
|
what is the function of the lipase of S. aureus?
|
degrades lipids on the skin surface
its expression is correlated with the ability of the bacteria to produce skin abscesses |
|
|
what is the function of protein A on the surface of Staphylococci?
|
binds to Fc portion of immunoglobulins, allowing the organism to escape antibody-mediated killing
|
|
|
what is S. aureus alpha toxin?
|
a membrane-damaging/hemolytic toxin
a pore-forming protein that intercalates into the plasma membrane of host cells and depolarizes them |
|
|
what is S. aureus beta-toxin?
|
a membrane damaging (hemolytic) toxin
a sphingomyelinase |
|
|
what is S. aureus delta toxin?
|
a membrane damaging (hemolytic) toxin
a detergent-like peptide |
|
|
what is S. aureus gamma toxin?
|
a membrane damaging (hemolytic) toxin
lyses erythrocytes |
|
|
what is leukocidin?
|
membrane damaging (hemolytic) toxin produced by S. aureus
lyses phagocytic cells |
|
|
what are the exfoliative A and B toxins produced by S. aureus?
|
serine proteases that cleave desmoglein 1, which is part of the desmosomes that hold epidermal cells tightly together
cleavage of desmoglein 1 causes keratinocytes to detach from one another and the underlying skin, resulting in a loss of barrier function that often leads to secondary skin infections |
|
|
where does exfoliation caused by S. aureus occur?
|
locally at the site of infection (bullous impetigo)
widespread, when secreted toxin causes disseminated loss of superficial epidermis (staphylococcal scalded-skin syndrome) |
|
|
what is bullous impetigo?
|
exfoliation, caused by staphylococcal exfoliative A and B toxins, that occurs locally at the site of infection
exfoliation = detachment of keratinocytes from each other and from the underlying skin, causing a loss of barrier function |
|
|
what is scalded skin syndrome?
|
widespread exfoliation, caused by staphylococcal exfoliative A and B toxins, that causes disseminated loss of superficial epidermis
exfoliation = detachment of keratinocytes from each other and from the underlying skin, causing a loss of barrier function |
|
|
what conditions are caused by superantigens produced by S. aureus?
|
food poisoning
toxic shock syndrome |
|
|
with what is toxic shock syndrome (TSS) associated with in the public eye?
|
the use of hyperabsorbent tampons, which became colonized with S. aureus during use
it has become clear though, that TSS can be caused by growth of S. aureus at many sites, most commonly the vagina and infected surgical sites |
|
|
how does TSS present?
|
TSS = toxic shock syndrome
hypotension renal failure coagulopathy liver disease respiratory distress generalized erythematous rash soft tissue necrosis at the site of infection |
|
|
what two bacteria can cause toxic shock syndrome?
|
Staphylococcus aureus
Streptococcus pyogenes |
|
|
what conditions are caused by superantigens produced by S. aureus?
|
food poisoning
toxic shock syndrome |
|
|
how do superantigens cause problems?
|
bind to conserved portions of MHC molecules and to relatively conserved portions of T-cell receptor beta chains, which stimulates up to 20% of T lymphocytes
stimulation of T lymphocytes causes release of large amounts of cytokines (TNF and IL-1), which produces a condition similar to septic shock |
|
|
with what is toxic shock syndrome (TSS) associated with in the public eye?
|
the use of hyperabsorbent tampons, which became colonized with S. aureus during use
it has become clear though, that TSS can be caused by growth of S. aureus at many sites, most commonly the vagina and infected surgical sites |
|
|
how does TSS present?
|
TSS = toxic shock syndrome
hypotension renal failure coagulopathy liver disease respiratory distress generalized erythematous rash soft tissue necrosis at the site of infection |
|
|
what conditions are caused by superantigens produced by S. aureus?
|
food poisoning
toxic shock syndrome |
|
|
what two bacteria can cause toxic shock syndrome?
|
Staphylococcus aureus
Streptococcus pyogenes |
|
|
how do superantigens cause problems?
|
bind to conserved portions of MHC molecules and to relatively conserved portions of T-cell receptor beta chains, which stimulates up to 20% of T lymphocytes
stimulation of T lymphocytes causes release of large amounts of cytokines (TNF and IL-1), which produces a condition similar to septic shock |
|
|
with what is toxic shock syndrome (TSS) associated with in the public eye?
|
the use of hyperabsorbent tampons, which became colonized with S. aureus during use
it has become clear though, that TSS can be caused by growth of S. aureus at many sites, most commonly the vagina and infected surgical sites |
|
|
how does TSS present?
|
TSS = toxic shock syndrome
hypotension renal failure coagulopathy liver disease respiratory distress generalized erythematous rash soft tissue necrosis at the site of infection |
|
|
what two bacteria can cause toxic shock syndrome?
|
Staphylococcus aureus
Streptococcus pyogenes |
|
|
how do superantigens cause problems?
|
bind to conserved portions of MHC molecules and to relatively conserved portions of T-cell receptor beta chains, which stimulates up to 20% of T lymphocytes
stimulation of T lymphocytes causes release of large amounts of cytokines (TNF and IL-1), which produces a condition similar to septic shock |
|
|
around what are staphylococcal skin infections centered?
|
hair follicles
(excluding impetigo) |
|
|
what is a furuncle?
|
aka a boil
a focal suppurative inflammation of the skin and subcutaneous tissue, that begins in a single hair follicle and develops into a growing and deepening abscess that eventually "comes to a head" by thinning and rupturing the overlying skin occurs either solitary or multiple or recurrent in successive crops most frequent in moist, hairy areas (face, axillae, groin, legs, and submammary folds) |
|
|
what is a carbuncle?
|
deeper suppurative infection than a boil, that spreads laterally beneath the deep subcutaneous fascia and then burrows superficially to erupt in multiple adjacent skin sinuses
typically appear beneath the skin of the upper back and posterior neck (fascial planes favor their spread) |
|
|
where are furuncles (boils) typically found?
|
moist, hairy locations
- face - axillae - groin - legs - submammary folds |
|
|
where are carbuncles typically found?
|
beneath the skin of the upper back and posterio neck
the fascial planes in these areas favor the spread of carbuncles |
|
|
what is hidradenitis?
|
chronic suppurative infection of apocrine glands, most often in the axilla
caused by S. aureus |
|
|
what is paronychia?
|
very painful infection of the nail bed
can be caused by S. aureus |
|
|
what are felons?
|
very painful infections of the palmar side of fingertips
can be caused by S. aureus |
|
|
how do staphylococcal lung infections compare to those caused by pneumococcal lung infections?
|
similar, but S. aureus lung infections cause much more tissue damage
|
|
|
in what type of patients are S. aureus lung infections typically found?
|
patients with a hematogenous source, such as an infected thrombus
OR patients with predisposing conditions, such as influenza |
|
|
what is Ritter disease?
|
aka staphylococcal scalded skin syndrome
sunburn-like rash over entire body that evolves into fragile bullae that lead to partial or total skin loss most frequently occurs in children with staphylococcal infection of the nasopharynx or skin |
|
|
at what layer of the skin does the desquamation of the epidermis occur in Ritter disease?
|
aka staphylococcal scalded skin syndrome
granulosa layer |
|
|
what distinguishes Ritter disease (staphylococcal scalded skin syndrome) from Lyell's disease (toxic epidermal necrolysis)?
|
Ritter disease - desquamation of epidermis at granulosa layer
Lyell's disease - desquamation of epidermis at epidermal-dermal junction |
|
|
what is Lyell's disease?
|
aka toxic epidermal necrolysis
rare, life-threatening dermatological condition that is usually induced by a reaction to medications (drug induced hypersensitivity) characterized by the detachment of the top layer of skin (the epidermis) from the lower layers of the skin (the dermis) all over the body |
|
|
to what antibiotics is MRSA resistant?
|
all available beta-lactam cell-wall synthesis inhibitors
- penicillins - cephalosporins |
|
|
why has empiric treatment of staphylococcal infections with beta-lactam antibiotics become less effective?
|
where previously MRSA was mainly found in healthcare-associated infections, community-acquired MRSA infections are becoming more and more common in many areas
|
|
|
what makes community-acquired strains of MRSA particularly virulent?
|
these strains of S. aureus commonly produce a potent membrane damaging toxin, which kills leukocytes
|
|
|
what type of bacteria are streptococci?
|
gram-positive cocci
grow in pairs or chains produce lactic acid |
|
|
what post-infectious syndromes are caused by Streptococci?
|
rheumatic fever (S. pyogenes)
immune complex glomerulonephritis erythema nodosum |
|
|
how are beta-hemolytic streptococci typed?
|
according to their surface carbohydrate (Lancefield) antigens
group A = S. pyogenes group B = S. agalactiae |
|
|
what is group A streptococcus? what does it cause?
|
group A streptococcus = S. pyogenes
CAUSES: - pharyngitis (strep throat) - scarlet fever - erysipelas - impetigo - rheumatic fever - toxic shock syndrome - glomerulonephritis |
|
|
what is group B streptococcus? what does it cause?
|
group B streptococcus = S. agalactiae
- colonizes the female genital tract (UTIs) - causes sepsis in neonates - causes meningitis in neonates - causes chorioamnionitis in pregnancy |
|
|
what is the most important alpha-hemolytic streptococcus?
|
S. pneumoniae
common cause of community-acquired pneumonia and meningitis in adults |
|
|
what are the alpha-hemolytic streptococci?
|
S. pneumoniae
Viridans Group (location preference in parenthesis): - S. mutans - S. mitis (cheek region) - S. sanguinis (no preference of location) - S. salivarius (dorsal tongue) |
|
|
what is the viridans group of streptococci?
|
alpha hemolytic and non-hemolytic streptococci that are normal oral flora; they are also a common cause of endocarditis
(s. mutans, S. mitis, S. sanguinis, S. salivarius) |
|
|
what is scarlet fever?
|
a disease caused by exotoxin released by Streptococcus pyogenes
|
|
|
what is erysipelas?
|
an acute streptococcus bacterial infection of the deep epidermis with lymphatic spread
|
|
|
what is the major cause of dental caries?
|
Streptococcus mutans
|
|
|
how are Streptococcal infections diagnosed?
|
culture
rapid antigen test for pharyngitis (strep throat) |
|
|
what type of bacteria are enterococci?
|
gram-positive cocci
grow in chains often resistant to commonly used antibiotics significant cause of endocarditis and UTIs |
|
|
what species of streptococci have capsules that resist phagocytosis?
|
S. pyogenes
S. agalactiae S. pneumoniae |
|
|
what are the virulence factors of S. pyogenes?
|
capsule that resists phagocytosis
M protein (prevents phagocytosis) C5a peptidase (degrades chemotactic peptide) phage-encoded exotoxin (causes fever and rash in scarlet fever) |
|
|
what causes the fever and rash that are common in scarlet fever?
|
phage-encoded exotoxin produced by S. pyogenes
|
|
|
what causes post-streptococcal rheumatic fever?
|
anti-streptococcal M protein antibodies and T cells that cross-react with cardiac proteins
|
|
|
why are virulent S. pyogenes referred to as flesh-eating bacteria?
|
cause a rapidly progressive necrotizing fasciitis
|
|
|
what is pneumolysin?
|
a cytosolic bacterial protein of Streptococcus pneumoniae that is released on disruption of the bacterial cell
it inserts into host cell membranes and lyses them, greatly increasing tissue damage it also activates the classical pathway of complement, reducing complement available for opsonization of bacteria |
|
|
how does S. mutans produce dental caries?
|
metabolizes sucrose to lactic acid, which causes demineralization of tooth enamel
secretes high-molecular-weight glucans, which promote aggregation of bacteria and plaque formation |
|
|
what are the virulence factors of enterococci?
|
antiphagocytic capsule
production of enzymes that cleave host tissues resistance to antibiotics (including vancomycin) |
|
|
what is the major contributor to the emergence of enterococci as pathogens?
|
resistance to antibiotics, including broad-spectrum vancomycin
**other than this, enterococci are considered relatively low virulence bacteria** |
|
|
what characterizes streptococcal infections?
|
interstitial neutrophilic infiltrates with minimal destruction of host tissues
|
|
|
what skin lesions are caused by streptococci?
|
furuncles (boils)
carbuncles impetigo similar to staphylococci, but less likely to cause the formation of discrete abscesses |
|
|
what is the most common streptococcal infection among middle-aged persons in warm climates?
|
Erysipelas
cutaneous rash on the face or, less frequently, on the body or an extremity caused by exotoxins from superficial infection with S. pyogenes |
|
|
what are the characteristic features of Erysipelas?
|
rapidly spreading erythematous cutaneous swelling that may begin on the face or, less frequently, on the body or an extremity
the rash has a sharp, well-demarcated, serpiginous border, and may form a "butterfly" distribution on the face |
|
|
define serpiginous
|
slowly progressive or "creeping"
regarding skin ailments in particular, this means that such a disease leaves scar tissue below while continuing to affect the skin above |
|
|
what is seen on histologic examination of Erysipelas rash?
|
diffuse, edematous, neutrophilic inflammatory reaction in the dermis and epidermis extending into the subcutaneous tissues
microabscesses may be formed, but tissue necrosis is usually minor |
|
|
what is the major antecedent of post-streptococcal glomerulonephritis?
|
streptococcal pharyngitis
aka strep throat |
|
|
what are the characteristic features of Streptococcal pharyngitis?
|
edema
epiglottic swelling punctate abscesses of the tonsillar crypts sometimes, cervical lymphadenopathy swelling associated with severe pharyngeal infection may encroach on the airways, especially if there is peritonsillar or retropharyngeal abscess formation |
|
|
when is Scarlet fever most common?
|
between ages of 3 and 15 years
associated with pharyngitis caused by S. pyogenes |
|
|
what are the characteristic features of scarlet fever?
|
punctate erythematous rash that is most prominent over the trunk and inner aspects of the arms and legs
face is also involved, but usually a small area about the mouth remains relatively unaffected to produce a circumoral pallor inflammation of the skin usually leads to hyperkeratosis and scaling during defervescence |
|
|
define defervescence
|
abatement of a fever as indicated by a decrease in bodily temperature
|
|
|
which types of tonsils are visible in the mouth?
|
palatine tonsils are visible on examination of the mouth
|
|
|
what are the frequent disease presentations of S. aureus?
|
abscesses
cellulitis pneumonia sepsis |
|
|
what are the frequent disease presentations of S. epidermidis?
|
abscesses
cellulitis pneumonia sepsis |
|
|
what are the frequent disease presentations of S. pyogenes?
|
pharyngitis (strep throat)
erysipelas scarlet fever |
|
|
what are the frequent disease presentations of S. pneumoniae?
|
lobar pneumonia
meningitis |
|
|
what organism is also known as pneumococcus?
|
Streptococcus pneumoniae
|
|
|
what organism is also known as meningococcus?
|
Neisseria meningitidis
|
|
|
what organism is also known as gonococcus?
|
Neisseria gonorrhoea
|
|
|
what are the frequent disease presentations of Neisseria meningitidis?
|
meningitis
|
|
|
what are the frequent disease presentations of Neisseria gonorrhoea?
|
gonorrhea
|
|
|
what are the frequent disease presentations of E. coli?
|
UTI
wound infection abscess pneumonia sepsis shock endocarditis |
|
|
what are the important opportunistic bacterial infections?
|
Escherichia coli
Klebsiella pneumoniae Enterobacter aerogenes Proteus mirabilis Proteus morgagni Serratia marcescens Pseudomonas aeruginosa Clostridium difficile Mycobacterium tuberculosis Mycobacterum kansasii |
|
|
what are the frequent disease presentations of L. pneumophila?
|
Legionella pneumophila produces Legionnaires disease
|
|
|
what are the frequent disease presentations of B. fragilis?
|
Bacteroides fragilis produces anaerobic infection
|
|
|
what are the important bacterial infections by pyogenic cocci?
|
S. aureus
S. epidermidis S. pyogenes S. pneumoniae N. meningitidis N. gonorrhoea |
|
|
what are the important gram-negative bacterial infections?
|
E. coli
Klebsiella pneumoniae Enterobacter aerogenes Proteus spp. (mirabilis and morgagni) Serratia marcescens Pseudomonas aeruginosa Bacteroides fragilis Legionella pneumophila |
|
|
what are the important contagious childhood bacterial diseases?
|
Heamophilus influenzae (meningitis, URT & LRT infections)
Bordetella pertussis (whooping cough) Corynebacterium diphtheriae (diphtheria) |
|
|
what are the important enteric bacterial infections?
|
Enteropathogenic E. coli
Shigella spp. Vibrio cholerae Campylobacter jejuni Campylobacter coli Yersinia enterocolitica Salmonella spp. |
|
|
what are the frequent disease presentations of S. typhi?
|
Salmonella typhi
causes Typhoid fever |
|
|
what are the frequent disease presentations of C. tetani?
|
Clostridium tetani
causes tetanus (lockjaw) |
|
|
what are the frequent disease presentations of C. botulinum?
|
Clostridium botulinum
causes botulism (paralytic food poisoning) |
|
|
what are the frequent disease presentations of C. perfringens?
|
Clostridium perfringens
gas gangrene necrotizing cellulitis |
|
|
what are the frequent disease presentations of C. septicum?
|
Clostridium septicum
gas gangrene necrotizing cellulitis |
|
|
what are the frequent disease presentations of C. difficile?
|
Closridium difficile
Pseudomembranous colitis (antibiotic-associated diarrhea) |
|
|
what are the frequent disease presentations of B. anthracis?
|
Bacillus anthracis
Anthrax |
|
|
what are the frequent disease presentations of Yersinia pestis?
|
bubonic plague
|
|
|
what are the frequent disease presentations of Francisella tularensis?
|
tularemia
|
|
|
what are the frequent disease presentations of Brucella spp.?
|
Brucella melitensis
Brucella suis Brucella abortus Brucellosis (undulant fever) |
|
|
what are the frequent disease presentations of Borrelia recurrentis?
|
Relapsing fever
|
|
|
what are the frequent disease presentations of Borrelia burgdorferi?
|
Lyme disease
|
|
|
what are the frequent disease presentations of Treponema pallidum?
|
Syphilis
|
|
|
what are the frequent disease presentations of Nocardia asteroides?
|
Nocardiosis
|
|
|
what are the frequent disease presentations of Actinomyces israelii?
|
actinomycosis
|
|
|
what are the important bacterial actinomycetaceae infections?
|
Nocardia asteroides (Nocardiosis)
Actinomyces israelii (Actinomycosis) |
|
|
what organism causes Diphtheria?
|
Corynebacterium diphtheriae
gram-positive rod with clubbed ends |
|
|
what type of bacteria is Corynebacterium diphtheriae?
|
slender, gram-positive rod with clubbed ends
|
|
|
how is Corynebacterium diphtheriae transmitted?
|
aerosolized droplets
skin exudate |
|
|
what is the only toxin produced by Corynebacterium diphtheriae?
|
phage-encoded A-B toxin that blocks host cell protein synthesis
A domain catalyzes the covalent transfer of ADP-ribose to elongation factor-2 (EF-2), thereby inhibiting the essential function of EF-2 in translation |
|
|
how potent is the diphtheria toxin?
|
a single molecule can kill a cell by ADP-ribosylating, and thus inactivating, more that a million EF-2 molecules
|
|
|
what is the effect of immunization with diphtheria toxoid?
|
protects immunized individuals from lethal effects of diphtheria toxin
**does NOT prevent colonization with C. diphtheriae** |
|
|
what kind of vaccine is the diphtheria vaccine?
|
formalin-fixed toxin vaccine consisting of diphtheria toxoid
|
|
|
where does inhaled C. diphtheriae proliferate?
|
at the site of attachment on the mucosa of the nasopharynx, oropharynx, larynx, or trachea
forms satellite lesions in the esophagus or lower airways |
|
|
how does C. diphtheriae cause damage at the site of attachment?
|
releases exotoxin (diphtheria toxin) which causes necrosis of the epithelium, accompanied by an outpouring of a dense fibrinosuppurative exudate
coagulation of this exudate on the ulcerated necrotic surface creates a tough, dirty gray-black superficial membrane neutrophil infiltration is intense and accompanied by marked vascular congestion, interstitial edema, and fibrin exudation |
|
|
what happens when the diphtheria membrane sloughs off its inflamed and vascularized bed?
|
bleeding and asphyxiation
|
|
|
what happens to the diphtheria membrane when infection is controlled?
|
it is coughed up or removed by enzymatic digestion, and the inflammatory reaction subsides
|
|
|
other than local effects, what is caused by diphtheria exotoxin?
|
- generalized hyperplasia of the spleen and lymph nodes
- fatty change in myocardium with isolated myofiber necrosis - polyneuritis with degeneration of the myelin sheaths and axis cylinders - fatty change and focal necroses of parenchymal cells in the liver, kidneys, and adrenals |
|
|
what organism causes Listeriosis?
|
Listeria monocytogenes
gram-positive, facultative intracellular bacillus |
|
|
what kind of bacteria is Listeria monocytogenes?
|
gram-positive rod (bacillus)
facultative intracellular |
|
|
with what are mini-epidemics of Listeria monocytogenes infections linked?
|
dairy products*
chicken hot dogs |
|
|
what populations are particularly at risk for infection with Listeria monocytogenes?
|
pregnant women
neonates elderly immunosuppressed persons |
|
|
what is the result of Listeriosis in pregnant women?
|
aka L. monocytogenes infection
causes amnionitis that may result in abortion, stillbirth, or neonatal sepsis |
|
|
what is the result of Listeriosis in neonates?
|
disseminated disease (granulomatosis infantiseptica)
exudative meningitis |
|
|
what is the result of Listeriosis in immunosuppressed adults?
|
disseminated disease (granulomatosis infantiseptica)
exudative meningitis |
|
|
what are internalins?
|
leucine-rich proteins on the surface of Listeria monocytogenes
bind to E-cadherin on host epithelial cells and induce internalization of the bacterium |
|
|
what is listeriolysin O?
|
pore-forming protein produced by Listeria monocytogenes
helps bacterium in escape from the phagolysosome |
|
|
what proteins are used by Listeria monocytogenes to escape phagolysosomes?
|
listeriolysin O
two phospholipases |
|
|
what is ACTA?
|
bacterial surface protein of Listeria monocytogenes that binds to host cell cytoskeletal proteins and induces actin polymerization
the actin polymerization propels the bacterium into adjacent, uninfected cells |
|
|
what protein allows Listeria monocytogenes to "hijack" host cell actin cytoskeleton and "rocket" from one cell to the next?
|
ACTA
bacterial cell surface protein that binds host cell cytoskeletal proteins and induces actin polymerization, which propels the bacterium into adjacent, uninfected cells |
|
|
how do resting macrophages internalize L. monocytogenes?
|
C3 activated on the bacterial surface
(they fail to kill the bacteria) |
|
|
what is important about the action of macrophages in L. monocytogenes infection?
|
resting macrophages internalize L. monocytogenes through activated C3 on bacterial surface and fail to kill the bacteria
macrophages activated by IFN-gamma phagocytose and kill the bacteria |
|
|
what immune response is the major contributor to protection against L. monocytogenes?
|
IFN-gamma produced by NK cells and T cells
|
|
|
what type of inflammatory pattern is caused by acute infection with Listeria monocytogenes?
|
exudative pattern of inflammation with numerous neutrophils
|
|
|
what is the difference between the meningitis caused by L. monocytogenes and that caused by other pyogenic bacteria?
|
they are macroscopically and microscopically indistinguishable
|
|
|
if you find gram-positive, mostly intracellular, bacilli in the CSF, what is the most likely diagnosis?
|
meningitis caused by Listeria monocytogenes
|
|
|
what is seen in infants born with L. monocytogenes sepsis?
|
papular red rash over the extremities
listerial abscesses in the placenta smear of meconium shows gram-positive rods |
|
|
what lesions are seen in neonates and immunosuppressed adults infected with L. monocytogenes?
|
focal abscesses alternating with grayish or yellow nodules representing necrotic amorphous basophilic tissue debris
occurs in any organ, including lung, liver, spleen, and lymph nodes |
|
|
what organism causes anthrax?
|
Bacillus anthracis
large, spore-forming, gram-positive, rod-shaped bacterium |
|
|
what type of bacteria is Bacillus anthracis?
|
large, gram-positive rod
spore-forming |
|
|
how does B. anthracis make a potent biological weapon?
|
spores are ground to a fine powder
|
|
|
how is Bacillus anthracis typically transmitted?
|
exposure to contaminated/infected animals or animal products such as wool or hides
|
|
|
what are the three major anthrax syndromes?
|
cutaneous anthrax (95% of naturally occuring infections)
inhalational anthrax gastrointestinal anthrax (uncommon) |
|
|
what is cutaneous anthrax?
|
begins as a painless, pruritic papule that develops into a vesicle within 2 days
as the vesicle enlarges, striking edema may form around it, and regional lymphdenopathy develops after rupture of vesicle, the ulcer becomes covered with a characteristic black eschar, which dries and falls off as the person recovers caused by Bacillus anthracis bacteremia is rare |
|
|
what is inhalational anthrax?
|
Bacillus anthracis spores are inhaled and the organism is carried by phagocytes to lymph nodes where the spores germinate
release of toxins from germinated B. anthracis causes hemorrhagic mediastinitis after 1-6 day prodromal illness, there is abrupt onset of increased fever, hypoxis, and sweating frequent bacteremia and frequent meningitis develop rapidly leads to shock and death in 1-2 days |
|
|
what are the characteristics of the prodromal illness caused by inhalation of B. anthracis?
|
fever
cough chest/abdominal pain |
|
|
what is GI anthrax?
|
caused by eating undercooked meat contaminated with B. anthracis
initially causes nausea, abdominal pain, and vomiting, followed by severe, bloody diarrhea mortality is over 50% |
|
|
what are the virulence factors of Bacillus anthracis?
|
antiphagocytic polyglutamyl capsule
potent exotoxins (A-B toxins; A subunit can be edema factor or lethal factor, B subunit is protective antigen) |
|
|
what is known as "protective antigen" in relation to B. anthracis? why?
|
B subunit of anthrax toxin
antibodies against this protein protect animals against the toxin |
|
|
what is edema factor?
|
one of two alternate A subunits of anthrax toxin (aka EF)
once in the cytoplasm of cells, EF binds to calcium and calmodulin to form an adenylate cyclase active EF converts ATP to cAMP, which is an important signaling molecule to stimulate efflux of water from host cell, leading to interstitial edema |
|
|
what is lethal factor?
|
one of two alternate A subunits of anthrax toxin (aka LF)
once in the cytoplasm of cells, LF is a protease that destroys mitogen-activated protein kinase kinases (MAPKKs), which regulate the activity of MAPKs, which are important regulators of cell growth & differentiation |
|
|
what is the process by which anthrax toxin is introduced into cells?
|
B subunit (protective antigen) binds to a host cell-surface protein
host protease clips of a 20kD fragment remaining 63kD fragment self-associates to form a heptamer three A subunits bind (either EF or LF) to the B subunit heptamer complex is endocytosed low pH of endosome causes conformational change in B heptamer B heptamer forms selective channel in endosome membrane EF and LF move into the cytoplasm through selective channel |
|
|
what is the typical appearance of anthrax lesions at any site?
|
necrosis and exudative inflammation with infiltration of neutrophils and macrophages
|
|
|
diagnosis of what is suggested by the presence of large, boxcar-shaped gram-positive extracellular bacteria in chains?
|
Bacillus anthracis
|
|
|
what is seen in the mediastinum in patients with inhalational anthrax?
|
numerous foci of hemorrhage
hemorrhagic, enlarged hilar and peribronchial lymph nodes |
|
|
what is seen on microscopic examination of the lungs in a patient with inhalational anthrax?
|
perihilar interstitial pneumonia with infiltration of macrophages and neutrophils and pulmonary vasculitis
hemorrhagic lesions associated with vasculitis are present in about half of cases |
|
|
what is seen in mediastinal lymph nodes in a patient with inhalational anthrax?
|
lymphocytosis
macrophages with phagocytosed apoptotic lymphocytes fibrin-rich edema |
|
|
where is B. anthracis usually seen if in the lungs?
|
predominantly in the alveolar capillaries and venules
to a lesser degree, within the alveolar space |
|
|
where is B. anthracis found in fatal cases of inhalational anthrax?
|
spleen
liver intestines kidneys adrenals meninges |
|
|
what type of bacteria are Nocardia spp.?
|
aerobic, gram-positive rods
catalase positive stain with acid-fast staining grow in branched chains (look like mold, but are true bacteria) |
|
|
what bacteria forms thin aerial filaments resembling hyphae?
|
Nocardia spp.
|
|
|
where are Nocardia spp. typically found?
|
in the soil
|
|
|
what populations are particularly at risk for Nocardia infections?
|
immunocompromised people
|
|
|
what type of infections are caused by Nocardia asteroides?
|
respiratory infections
|
|
|
what type of infections are caused by Nocardia brasiliensis?
|
skin infections
|
|
|
what is a common sequelae to respiratory infection with Nocardia asteroides?
|
meningitis (CNS involvement), presumably after dissemination from the lungs
happens in about 1/5 N. asteroides infections |
|
|
what is the common thread in most patients with N. asteroides infection?
|
defects in T cell-mediated immunity, often due to prolonged steroid use, or HIV infection, or diabetes mellitus
|
|
|
how do respiratory infections with N. asteroides typically present?
|
indolent illness with fever, weight loss, and cough
often mistaken for TB or malignancy |
|
|
define indolent
|
causing little or no pain
|
|
|
how do CNS infections with N. asteroides typically present?
|
indolent illness with varying neurologic deficits depending on the site of infection
|
|
|
how do Nocardia spp. appear in tissue?
|
slender, gram-positive organisms arranged in branching filaments (chains)
irregular staining gives the filaments a beaded appearacne |
|
|
what bacteria will stain with acid-fast stains?
|
Mycobacterium spp.
Nocardia spp. |
|
|
since Actinomyces appear similar to Nocardia on gram stain of tissue, how can you differentiate them?
|
Nocardia will stain with acid-fast stains, while Actinomyces will not
|
|
|
what type of inflammatory response is elicited by Nocardia spp.?
|
at any site of infection, a suppurative response with central liquefaction and surrounding granulation and fibrosis
granulomas do not form |
|
|
how are gram-negative bacterial infections usually diagnosed?
|
culture
|
|
|
what type of bacteria are Neisseria spp.?
|
gram-negative diplococci, flattened on adjoining sides (the pair has the shape of a coffee bean)
aerobic catalase-positive oxidase-positive |
|
|
what types of sugars can Neisseria spp. use to make lactic acid?
|
N. gonorrhoeae - glucose only
N. meningitidis - glucose and maltose |
|
|
on what media do Neisseria spp. grow best?
|
enriched media such as lysed sheep's blood agar ("chocolate" agar)
|
|
|
what are the two clinically significant species of Neisseria?
|
N. meningitidis
N. gonorrhoeae |
|
|
why is N. meningitidis important?
|
significant cause of bacterial meningitis, particularly among children younger than 2 years of age
common colonizer of oropharynx |
|
|
how is N. meningitidis transmitted?
|
respiratory droplets
|
|
|
where is N. meningitidis colonization commonly found?
|
oropharynx in about 10% of the population at any one time
each episode of colonization lasts, on average, several months immune response leads to elimination of organism in most people and is protective against subsequent disease with same serotype of bacteria |
|
|
how many serotypes are there of Neisseria meningitidis?
|
at least 13
|
|
|
when does invasive disease, caused by N. meningitidis, typically occur?
|
when people encounter new strains to which they are not immune:
- young children - young adults in military barracks - young adults in college dormitories |
|
|
how does N. meningitidis cause meningitis?
|
invades respiratory epithelial cells and travels to the basolateral side to enter the blood
the capsule of the bacteria inhibits opsonization and destruction of bacteria by complement after escaping host response, invades CNS |
|
|
inherited defects in what part of innate immunity cause severe infections?
|
defects in complement proteins, C5-C9, which form the membrane attack complex
|
|
|
what is the mortality of N. meningitidis infection?
|
10%
|
|
|
why is N. gonorrhoeae important?
|
significant cause of STD, infecting about 700,000 people each year in the US
second most common bacterial causative agent of STDs, behind Chlamydia trachomatis |
|
|
what are the two most common bacterial causative agents of STDs?
|
1) Chlamydia trachomatis
2) Neisseria gonorhoeae |
|
|
what is caused by infection with N. gonorhoeae in men?
|
urethritis
|
|
|
what is caused by infection with N. gonorhoeae in women?
|
asymptomatic infection that may go unnoticed and lead to pelvic inflammatory disease if untreated
PID can cause infertility or ectopic pregnancy |
|
|
how is infection with N. gonorhoeae diagnosed?
|
PCR tests
culture |
|
|
where are local manifestations of N. gonorrhoeae seen?
|
genital or cervical mucosa, pharynx, or anorectum
|
|
|
in what population of patients are N. gonorrhoeae infections more likely to become disseminated?
|
those patients lacking complement proteins, C5-C9, that form the membrane attack complex
|
|
|
what is caused by disseminated infection with N. gonorrhoeae in adults and adolescents?
|
septic arthritis accompanied by a rash of hemorrhagic papules and pustules
|
|
|
what is caused by disseminated infection with N. gonorrhoeae in neonates?
|
blindness and, rarely, sepsis
eye infection is preventable by instillation of silver nitrate or antibiotics in newborn's eyes, but is still an important cause of blindness in some developing nations |
|
|
how do Neisseria spp. evade the host immune system?
|
antigenic variation
(multiple serotypes and special genetic mechanisms which permit a single bacterial clone to change its expressed antigens) |
|
|
where do Neisseria spp. invade?
|
nonciliated epithelial cells at the site of entry (nasopharynx, urethra, or cervix)
|
|
|
what two surface proteins of Neisseria spp. undergo antigenic variation?
|
pili proteins
OPA proteins **both are involved in binding bacteria to host cells** |
|
|
how are Neisserial pili proteins altered?
|
genetic recombination
pili are composed of polypeptides encoded by the pili gene, which consists of a promoter and coding sequences for 10-15 pili protein variants at any point in time, only one of these coding sequences is juxtaposed to the promoter, allowing it to be expressed periodically, homologous recombination shuttles one of the other coding sequences next to the promoter, resulting in expression of a different pili variant if only part of the second coding sequence is swapped, an entirely new chimeric variant is created |
|
|
what mediates the adherence of N. gonorrhoeae to epithelial cells initially?
|
long pili, which bind to CD46, a complement regulatory protein expressed on all human nucleated cells
|
|
|
how are Neisserial OPA proteins altered?
|
N. gonorrhoeae has 3/4 genes for OPA proteins, and N. meningitidis has up to 12
Each OPA gene has several repeats of a 5-nucleotide sequence, which are frequently deleted or duplicated, shifting the reading frame of the gene so that it encodes new sequences, or introducing stop codons this allows Neisseria spp. to express none, one, or several OPA genes at a time |
|
|
what are OPA proteins?
|
named OPA proteins because they make bacterial colonies opaque
proteins located in the outer membrane of Neisseria spp. that increase binding to epithelial cells and promote entry of bacteria into cells |
|
|
what organism causes Whooping Cough?
|
Bordetella pertussis
gram-negative coccobacillus |
|
|
what type of bacteria is Bordetella pertussis?
|
gram-negative coccobacillus (sphere/rod combination)
aerobic oxidase positive urease negative nitrase negative citrate negative non-motile grow in diplococci arrangement |
|
|
what bacteria are coccobacilli?
|
Bordetella pertussis
Haemophilus influenzae Chlamydia trachomatis |
|
|
what is whooping cough?
|
acute, highly communicable illness characterized by paroxysms of violent coughing followed by a loud inspiratory "whoop"
|
|
|
what type of vaccine is the pertussis vaccine?
|
killed bacteria
acellular vaccine (less likely to produce febrile state) |
|
|
why have rates of pertussis been increasing in the United States, even though effective vaccines are available?
|
antigenic divergence of clinical strains from vaccine strains
waning immunity in young adults |
|
|
how is diagnosis of whooping cough made?
|
PCR
culture is less sensitive |
|
|
where does B. pertussis invade?
|
colonizes brush border of bronchial epithelium
invades macrophages |
|
|
what gene locus of B. pertussis coordinates the expression of virulence factors?
|
Bordetella virulence gene locus (bvg locus)
|
|
|
what is BVGS?
|
a transmembrane protein in Bordetella pertussis bacteria that "senses" signals that induce expression of virulence factors, and on activation phosphorylates the protein BVGA, which regulates transcription of mRNA for adhesins and toxins
|
|
|
what is BVGA?
|
protein in Bordetella pertussis bacteria that regulates transcription of mRNA for adhesins and toxins
phosphorylated by BVGS |
|
|
what is the function of the filamentous hemagglutinin adhesin on the cell surface of B. pertussis?
|
binds to carbohydrates on the surface of respiratory epithelial cells, as well as to CR3 (Mac-1) integrins on macrophages
|
|
|
how does pertussis toxin paralyze cilia?
|
pertussis toxin ADP-ribosylates and inactivates guanine nucleotide-binding proteins, so these G proteins no longer transduce signals from host plasma membrane receptors
|
|
|
what is pertussis toxin?
|
exotoxin produced by Bordetella pertussis that paralyzes the cilia of the respiratory tract
it is composed of five distinct proteins, including catalytic peptide S1, which shares homology with catalytic peptides of cholera toxin and E. coli heat-labile toxin |
|
|
what is the morphology of Bordetella pertussis infection?
|
laryngotracheobronchitis that features bronchial mucosal erosion, hyperemia, and copious mucopurulent exudate in severe cases
unless superinfected, alveoli remain open and intact striking peripheral lymphocytosis hypercellularity and enlargement of mucosal lymph follicles and peribronchial lymph nodes |
|
|
what type of bacteria is Pseudomonas aeruginosa?
|
gram-negative bacillus (rod)
aerobic |
|
|
patients with what three conditions are likely to have a fatal infection from Pseudomonas aeruginosa?
|
cystic fibrosis
severe burns neutropenia |
|
|
how does P. aeruginosa cause death in many cystic fibrosis patients?
|
chronic infection causes pulmonary failure
|
|
|
why are infections with Pseudomonas aeruginosa difficult to treat?
|
P. aeruginosa is very resistant to antibiotics
|
|
|
where is P. aeruginosa commonly acquired?
|
hospitals (common nosocomial infection)
has been cultured from washbasins, respirator tubing, nursery cribs, bottles containing antiseptics |
|
|
what is the link between P. aeruginosa and contact lenses?
|
Pseudomonas aeruginosa causes corneal keratitis in people who wear contact lenses
|
|
|
what is the link between P. aeruginosa and IV drug abusers?
|
Pseudomonas aeruginosa causes endocarditis and osteomyelitis in IV drug abusers
|
|
|
in what patients does P. aeruginosa cause external otitis?
|
external otitis = swimmer's ear
healthy individuals diabetics (more severe) |
|
|
how does P. aeruginosa bind to epithelial cells and lung mucin?
|
pili
adherence proteins |
|
|
how does P. aeruginosa cause the signs and symptoms of gram-negative sepsis?
|
expresses an endotoxin
|
|
|
what is alginate?
|
a mucoid exopolysaccharide produced by Pseudomonas aeruginosa
secreted in the lungs of people with cystic fibrosis to form a slimy biofilm that protects the bacteria from antibodies, complement, phagocytes, and antibiotics |
|
|
what is the function of exotoxin A expressed by P. aeruginosa?
|
it inhibits protein synthesis by ADP-ribosylating EF-2, the ribosomal protein
similar to diphtheria toxin |
|
|
what is the function of exoenzyme S expressed by P. aeruginosa?
|
ADP-ribosylates RAS and other G proteins that regulate cell growth and metabolism
|
|
|
how does P. aeruginosa lyse red blood cells?
|
secretes a phospholipase C
|
|
|
how does P. aeruginosa degrade pulmonary surfactant?
|
secretes a phospholipase C
|
|
|
how does P. aeruginosa degrade IgGs?
|
secretes an elastase
|
|
|
how does P. aeruginosa degrade extracellular matrix proteins?
|
secretes an elastase
|
|
|
what causes the vascular lesions that are characteristic of P. aeruginosa infection?
|
P. aeruginosa produces iron-containing compounds that are extremely toxic to endothelial cells and so cause the vascular lesions
|
|
|
what are the virulence factors of P. aeruginosa?
|
1) alginate (mucoid exopolysaccharide)
2) exotoxin A (like diphtheria toxin) 3) exoenzyme S (inhibits cell metabolism) 4) secrete phospholipase C 5) secrete elastase 6) iron-containing compounds (toxic to endothelial cells) |
|
|
what is the morphology of Pseudomonas pneumonia?
|
necrotizing pneumonia that is distributed through the terminal airways in a fleur-de-lis pattern
striking pale necrotic centers with red, hemorrhagic peripheral areas |
|
|
what is seen on microscopic examination of pneumonia caused by Pseudomonas?
|
masses of organisms clouding the tissue with a bluish haze, concentrating in the walls of blood vessels, where host cells undergo coagulative necrosis
|
|
|
what infection is strongly suggested by gram-negative vasculitis accompanied by thrombosis and hemorrhage, when seen in lung?
|
although not pathognomic, this is highly suggestive of P. aeruginosa pneumonia
|
|
|
what is the frequent result of bronchial obstruction by mucus plugging and subsequent P. aeruginosa infection in cystic fibrosis patients?
|
bronchiectasis and pulmonary fibrosis
even despite antibiotic treatment and host immune response |
|
|
what is ecthyma gangrenosum?
|
an infection of the skin typically caused by Pseudomonas aeruginosa
presents as a round or oval lesion, 1 cm to 15 cm in diameter, with a halo of erythema a necrotic center is usually present with a surrounding erythematous edge, representing where the organism invaded blood vessels and caused infarctions |
|
|
what does P. aeruginosa do in skin burns?
|
proliferates widely, penetrating deeply into the veins and spreading hematogenously
leaves well-demarcated necrotic and hemorrhagic oval skin lesions, called ecthyma gangrenosum DIC often follows the bacteremia |
|
|
what organism causes the plague?
|
Yersinia pestis
gram-negative, facultative intracellular bacterium transmitted from rodents to humans by fleabites or, less often, from human to human by aerosols |
|
|
what type of bacteria is Yersinia pestis?
|
gram-negative bacillus (rod)
facultative intracellular facultative anaerobe urease negative lactose fermentation negative indole negative |
|
|
what bacteria has a safety-pin appearance on staining?
|
Yersinia pestis
has bipolar staining properties |
|
|
what is Black Death?
|
aka the plague
infection with Yersinia pestis |
|
|
describe the three great plague pandemics
|
killed 100 million people in Egypt and Byzantium in the 6th century
killed 25% of Europe's population in 14th & 15th centuries killed tens of millions of people in India, Myanmar, and China at the beginning of the 20th century |
|
|
How many cases of plague occur each year worldwide?
|
1000-3000
wild rodents in rural western US are infected and contribute 10-15 cases per year |
|
|
what two bacteria are genetically similar to Yersinia pestis? what conditions do they cause?
|
Yersinia enterocolitica
Yersinia pseudotuberculosis fecal-oral transmitted ileitis and mesenteric lymphadenitis |
|
|
where do pathogenic Yersinia proliferate?
|
within lymphoid tissue
|
|
|
what allows pathogenic Yersinia spp. to kill host phagocytes?
|
Yop virulon
a complex of genes that encodes proteins that assemble into a type III secretion system, which is a hollow syringe-like structure that projects from the bacterial surface, binds to host cells, and injects bacterial toxins, called Yops (Yersinia outercoat proteins) into the cell |
|
|
what is the Yop virulon?
|
complex of genes which enable pathogenic Yersinia spp. to kill host phagocytes
encodes proteins that assemble into a hollow syringe-like structure that projects from the bacterial surface, binds to host cells, and injects bacterial toxins (a type III secretion system) called Yops, or Yersinia outercoat proteins, into the cell |
|
|
what are the different Yersinia outercoat proteins (Yops) used to neutralize host phagocytes? what is the function of each?
|
YopE, YopH, YopT - block phagocytosis by inactivating molecules that regulate actin polymerization
YopJ - inhibit signaling pathways that are activated by LPS, blocking inflammatory cytokines |
|
|
how does Y. pestis ensure its own spread?
|
forms a biofilm that obstructs the gut of the infected flea, so that the flea must regurgitate before it feeds and thus infects the rodent or human that it is biting
|
|
|
what are the distinctive histologic features of Yersinia pestis?
|
1) massive proliferation of organisms
2) early appearance of protein-rich and polysaccharide-rich effusions with few inflammatory cells but with marked tissue swelling 3) necrosis of tissues and blood vessels with hemorrhage and thrombosis 4) neutrophilic infiltrates that accumulate adjacent to necrotic areas as healing begins |
|
|
what are the three presentations of Yersinia pestis infection?
|
bubonic plague - buboes (lymph node enlargement)
pneumonic plague - pneumonia septicemic plague - sepsis with striking neutrophilia |
|
|
where is an infected fleabite typically found in patients with bubonic plague?
|
on the legs
marked by a small pustule or ulcer draining lymph nodes enlarge dramatically w/in a few days (become soft, pulpy, and plum colored) enlarged lymph nodes may infarct or rupture through the skin |
|
|
how does pneumonic plague present?
|
severe, confluent, hemorrhagic and necrotizing bronchopneumonia, often with fibrinous pleuritis
|
|
|
how does septicemic plague present?
|
lymph nodes throughout the body as well as organs rich in mononuclear phagocytes develop foci of necrosis
fulminant bacteremias also induce DIC with widespread hemorrhages and thrombi |
|
|
what is Chancroid?
|
aka soft Chancre
acute, sexually transmitted, ulcerative infection caused by Hemophilus ducreyi one of the most common causes of genital ulcers in Africa and Southeast Asia |
|
|
where is Chancroid most common?
|
tropical and subtropical areas among lower socioeconomic groups and men who have regular contact with prostitutes
|
|
|
what is one of the most common causes of genital ulcers in Africa and Southeast Asia?
|
Chancroid
|
|
|
how prevalent is Chancroid in the United States?
|
uncommon
20-50 cases/year for last several years |
|
|
why is it probable that chancroid is underdiagnosed?
|
Hemophilus ducreyi must be cultured in special conditions and PCR-based tests are not widely available
|
|
|
what condition is caused by infection with Hemophilus ducreyi?
|
chancroid (soft chancre)
acute, sexually transmitted, ulcerative infection (causes genital ulcers) |
|
|
how does chancroid present?
|
4-7 days after inoculation, the person develops a tender, erythematous papule involving the external genitalia
in males, primary lesion is on penis in females, primary lesion is in vagina or periurethral area over several days, the surface of the primary lesion erodes to produce an irregular ulcer (more painful in males than females) |
|
|
how does the chancroid differ from the primary chancre of syphilis?
|
the ulcer of chancroid is not indurated, and multiple lesions may be present
|
|
|
what does the base of a chancroid ulcer look like?
|
covered by shaggy, yellow-gray exudate
|
|
|
what happens to lymph nodes in about 50% of cases of chancroid?
|
particularly those in the inguinal region become enlarged and tender within 1-2 weeks of primary inoculation
if untreated, the inflammed and enlarged nodes (buboes) may erode the overlying skin and produce chronic, draining ulcers |
|
|
what are buboes?
|
swelling of the lymph nodes
similar in appearance to a huge blister, and usually appears under the armpit, in the groin or on the neck found in infections such as bubonic plague, gonorrhea, tuberculosis or syphilis |
|
|
how does a chancroid ulcer appear microscopically?
|
superficial zone of neutrophilic debris and fibrin
underlying zone of granulation tissue containing areas of necrosis and thrombosed vessels dense, lymphoplasmacytic inflammatory infiltrate beneath the layer of granulation tissue |
|
|
what type of bacteria is Hemophilus ducreyi?
|
fastidious gram-negative coccobacillus
appear like "school of fish" on gram stain |
|
|
why is it difficult to demonstrate Hemophilus ducreyi in gram or silver stains of chancroid ulcers?
|
other bacteria that colonize the ulcer base often obscure the coccobacilli of H. ducreyi
|
|
|
what organism causes granuloma inguinale?
|
aka donovanosis
Klebsiella granulomatis |
|
|
what is donovanosis?
|
aka granuloma inguinale
chronic, sexually transmitted, inflammatory disease caused by Klebsiella granulomatis causes extensive scarring, often associated with lymph obstruction and lymphedema (elephantiasis) of external genitalia |
|
|
what is granuloma inguinale?
|
aka donovanosis
chronic, sexually transmitted, inflammatory disease caused by Klebsiella granulomatis causes extensive scarring, often associated with lymph obstruction and lymphedema (elephantiasis) of external genitalia |
|
|
what is the former name of Klebsiella granulomatosis?
|
Calymmatobacterium donovani
|
|
|
what condition is caused by Klebsiella granulomatis?
|
granuloma inguinale (aka donovanosis)
a chronic, sexually transmitted, inflammatory disease that causes lymph obstruction and lymphedema (elephantiasis) of the external genitalia if untreated |
|
|
what type of bacteria is Klebsiella granulomatis?
|
gram-negative bacillus (rod)
|
|
|
where is granuloma inguinale endemic?
|
aka donovanosis
endemic in rural areas in certain tropical and subtropical regions uncommon in US and western Europe |
|
|
how is granuloma inguinale diagnosed?
|
microscopic examination of smears or biopsy samples of the ulcer
culture of Klebsiella granulomatis is difficult, and PCR assays are still in development |
|
|
how does granuloma inguinale present?
|
begins as a raised, papular lesion on the moist, stratified squamous epithelium of the genitalia or, rarely, the oral mucosa or pharynx
lesion eventually ulcerates and develops abundant granulation tissue which is manifested as a protuberant, soft, painless mass as lesion enlarges, its borders become raised and indurated disfiguring scars may develop in untreated cases and are sometimes associated with urethral, vulvar, or anal strictures |
|
|
what is seen on microscopic examination of active Klebsiella granulomatis lesions?
|
marked epithelial hyperplasia at borders of ulcer, sometimes mimicking carcinoma
mixture of neutrophils and mononuclear inflammatory cells is present at the base of the ulcer and beneath the surrounding epithelium |
|
|
what stains can be used to demonstrate Klebsiella granulomatis?
|
giemsa stain - minute, encapsulated coccobacilli (Donovan bodies) in macrophages
silver stain |
|
|
what is pseudoepitheliomatous hyperplasia?
|
a type of epithelial hyperplasia associated with chronic inflammatory response
distinguished from squamous cell carcinoma by the lack of dysplastic cytologic characteristics |
|
|
what are Donovan bodies?
|
rod-shaped, oval organisms that can be seen in the cytoplasm of mononuclear phagocytes or histiocytes in tissue samples from patients with granuloma inguinale
encapsulated gram-negative rods of klebsiella granulomatis |
|
|
what type of bacteria are Mycobacteria spp.?
|
weakly gram-positive bacilli (rods)
slender aerobic grow in straight or branching chains acid fast |
|
|
what does it mean for a bacterium to be acid fast?
|
they will retain stains even on treatment with a mixture of acid and alcohol
|
|
|
what makes Mycobacterium spp. acid fast?
|
they have a unique waxy cell wall composed of mycolic acid
|
|
|
what is the reservoir of M. tuberculosis?
|
humans with active tuberculosis
|
|
|
what bacterium causes oropharyngeal and intestinal tuberculosis?
|
Mycobacterium bovis
-> acquired by drinking contaminated milk -> rare in countries where milk is routinely pasteurized -> still seen in countries that have tuberculous dairy cows and unpasteurized milk |
|
|
how many people are affected by tuberculosis?
|
1.7 billion ppl worldwide
8-10 million new cases each year 1.6 million deaths each year |
|
|
what are the two pathogenic organisms that have the highest mortality rates?
|
1) HIV
2) M. tuberculosis |
|
|
how many people have simultaneous infections with both HIV and M. tuberculosis?
|
10,000,000 people
|
|
|
why did the number of tuberculosis cases increase by 20% in the US between 1985 and 1992?
|
increase in the disease in ppl with HIV, immigrants, and those in jail or homeless shelters
|
|
|
how many new cases of TB are found in the US annually?
|
14,000
about half occur in foreign-born people |
|
|
what conditions cause TB to flourish?
|
poverty
crowding chronic debilitating illness |
|
|
what disease states increase the risk of developing tuberculosis?
|
diabetes mellitus
Hodgkin lymphoma chronic lung disease (particularly silicosis) chronic renal failure malnutrition alcoholism immunosuppression |
|
|
what is the difference between infection with M. tuberculosis and the disease, TB?
|
infection is the presence of organisms, which may or may not cause clinically significant disease
|
|
|
how is M. tuberculosis transmitted?
|
person-to-person transmission of airborne organisms from an active case to a susceptible host
|
|
|
what are the symptoms of primary tuberculosis?
|
in most people, it is asymptomatic
can present as: - fever - pleural effusion - tiny fibrocalcific nodule at the site of infection |
|
|
what is pleural effusion?
|
excess fluid that accumulates between the pleura, the fluid-filled space that surrounds the lungs
|
|
|
how can immunosuppression cause TB in patients that showed no active disease when previously exposed?
|
viable M. tuberculosis bacteria can remain dormant is small fibrocalcific lesions for decades
when immune defenses are lowered, the infection reactivates to produce communicable and potentially life-threatening disease |
|
|
what type of hypersensitivity reaction is elicited by the Mantoux skin test?
|
aka purified protein derivative (PPD)
aka tuberculin skin test delayed-type hypersensitivity (type IV) |
|
|
how soon after infection will a tuberculin skin test be positive? what is a positive skin test?
|
2-4 weeks
induction of a visible AND palpable induration that peaks in 48-72 hours signifies T cell-mediated immunity to mycobacterial antigens |
|
|
define induration
|
hardening of a normally soft tissue or organ, especially the skin, because of inflammation, infiltration of a neoplasm, or an accumulation of blood
|
|
|
does the PPD test differentiate between active TB and M. tuberculosis infection?
|
no
|
|
|
what can cause false negative PPD tests?
|
certain viral infections
sarcoidosis malnutrition Hodgkin lymphoma immunosuppression overwhelming active tuberculous disease |
|
|
what can cause false positive PPD tests?
|
infection by atypical mycobacteria
prior vaccination with BCG (attenuated strain of M. bovis) |
|
|
what is BCG?
|
Bacillus Calmette-Guerin
an attenuated strain of M. bovis that is used as a vaccine in some countries (not US) |
|
|
on what is the pathogenesis of TB in a previously unexposed, immunocompetent person depend?
|
development of anti-mycobacterial cell-mediated immunity
(confers resistance to bacteria and results in development of hypersensitivity to mycobacterial antigens) |
|
|
what causes caseating granulomas and cavitation in tuberculosis?
|
hypersensitivity that develops in concert with the protective host immune response to M. tuberculosis
|
|
|
what are the primary cells infected by M. tuberculosis?
|
macrophages
|
|
|
how does replication of M. tuberculosis differ early in infection vs. later in infection?
|
early - replicate essentially unchecked
later - cell response stimulates macrophages to contain proliferation of M. tuberculosis |
|
|
how does M. tuberculosis enter macrophages?
|
endocytosis mediated by mannose receptors (bind lipoarabinomannan)
complement receptors (CR3 binds opsonized mycobacteria) |
|
|
what is lipoarabinomannan?
|
aka LAM
a glycolipid in the cell wall of mycobacterium tuberculosis it is mannose-capped and therefore binds to mannose receptors on macrophages (allows endocytosis of bacteria, leading to replication within the macrophage) |
|
|
where in the macrophage does M. tuberculosis replicate?
|
within the phagosome by blocking fusion with the lysosome
|
|
|
how does M. tuberculosis block phagolysosome formation?
|
inhibits calcium signals and the recruitment and assembly of the proteins that mediated phagosome-lysosome fusion
|
|
|
what is seen in the earliest stage (<3 weeks) of primary tuberculosis in nonsensitized individuals?
|
bacteria proliferate in the pulmonary alveolar macrophages and airspaces, resulting in bacteremia and seeding of multiple sites
despite bacteremia, most ppl at this stage are asymptomatic or have mild flulike illness |
|
|
polymorphisms in what gene can cause ineffective immune response to M. tuberculosis?
|
NRAMP1 gene
NRAMP1 may inhibit microbial growth by limiting availability of ions needed by the bacteria |
|
|
what is NRAMP1?
|
transmembrane protein found in endosomes and lysosomes that pumps divalent cations (Fe2+) out of the lysosome
it inhibits microbial growth by limiting availability of ions needed by bacteria polymorphisms in this gene allow TB to progress due to absence of an effective immune response |
|
|
what is seen about three weeks after infection with M. tuberculosis in healthy individuals?
|
a T-helper 1 response is initiated by mycobacterial antigens that enter draining lymph nodes and are displayed to T cells and is mounted to activate macrophages to become bactericidal
|
|
|
on what cytokine is TH1 cell differentiation dependent?
|
IL12
|
|
|
how does M. tuberculosis stimulate release of IL-12?
|
M. tuberculosis makes several molecules that are ligands for TLR2
stimulation of TLR2 by these ligands promotes production of IL-12 by dendritic cells |
|
|
what is the critical mediator that enables macrophages to contain an M. tuberculosis infection?
|
IFN-gamma
stimulates formation of the phagolysosome in infected macrophages, exposing the bacteria to an inhospitable acidic environment stimulates expression of iNOS, which produces nitric oxide, capable of destroying several mycobacterial constituents (from cell wall to DNA) |
|
|
why is IFN-gamma critical in enabling macrophages to contain an M. tuberculosis infection?
|
stimulates formation of the phagolysosome in infected macrophages, exposing the bacteria to an inhospitable acidic environment
stimulates expression of iNOS, which produces nitric oxide, capable of destroying several mycobacterial constituents (from cell wall to DNA) |
|
|
what happens to macrophages activated by IFN-gamma?
|
differentiate into "epitheloid histiocytes" that characterize the granulomatous response, and may fuse to form giant cells
|
|
|
what reactions are orchestrated by TH1 response to M. tuberculosis?
|
stimulation of macrophages to kill mycobacteria
formation of granulomas formation of caseous necrosis |
|
|
what response halts an M. tuberculosis infection before significant tissue destruction or illness in most people?
|
granulomatous response
(differentiation of IFN-gamma activated macrophages into epitheloid cells, that may fuse to form giant cells) |
|
|
what causes tissue damage when M. tuberculosis infection progresses (due to advanced age or immunosuppression)?
|
ongoing immune response results in tissue destruction due to caseation and cavitation
|
|
|
what cytokine is produced by macrophages to recruit more monocytes?
|
TNF
|
|
|
risk of what is increased in patients with rheumatoid arthritis who are treated with a TNF antagonist?
|
tuberculosis reactivation
TNF is an important cytokine produced by macrophages to recruit more blood monocytes |
|
|
what cells produce IFN-gamma in response to TB infection?
|
TH1 cells (major)
NK-T cells that recognize mycobacterial lipid antigens bound to CD1 on APCs (minor) T cells that express gamma/delta T cell receptor (minor) |
|
|
what is CD1?
|
family of glycoproteins expressed on the surface of various human antigen-presenting cells
related to the class I MHC molecules involved in the presentation of lipid antigens to T cells |
|
|
what is the cost of the protective immune response against M. tuberculosis?
|
protective response = TH1 stimulation of macrophages
cost = hypersensitivity and tissue destruction |
|
|
what results from reactivation of M. tuberculosis infection?
|
rapid mobilization of a defensive reaction and increased tissue necrosis
|
|
|
what results from re-exposure to M. tuberculosis in a previously sensitized host?
|
rapid mobilization of a defensive reaction and increased tissue necrosis
|
|
|
tuberculin negativity in a previously tuberculin-positive individual is a sign of what?
|
loss of hypersensitivity
resistance to M. tuberculosis has faded |
|
|
what is primary tuberculosis?
|
the form of tuberculosis that develops in a previously unexposed, and therefore unsensitized, person
|
|
|
what percentage of people, newly infected with tuberculosis, develop clinically significant disease?
|
5%
|
|
|
what populations can develop primary tuberculosis more than once?
|
elderly and profoundly immunosuppressed persons who lose their immunity to M. tuberculosis
|
|
|
what is the source of M. tuberculosis in primary tuberculosis?
|
exogenous
respiratory droplets from an infected individual |
|
|
how does progressive primary tuberculosis differ from secondary tuberculosis?
|
progressive primary tuberculosis resembles an acute bacterial pneumonia, with lower and middle lobe consolidation, hilar adenopathy, and pleural effusion; cavitation is rare, especially in ppl with severe immunosuppression
secondary tuberculosis presents as apical disease with cavitation |
|
|
what is the result of lymphohematogenous dissemination of M. tuberculosis?
|
tuberculous meningitis
miliary tuberculosis |
|
|
what is secondary tuberculosis?
|
pattern of disease that arises in a previously sensitized host
may follow shortly after primary TB, but more commonly appears many years after initial infection, usually when host resistance is weakened |
|
|
what are the sources of secondary TB?
|
most commonly - reactivation of a latent infection
can be the result of exogenous reinfection in the face of waning host immunity or when a large inoculum of virulent bacilli overwhelms the host immune system |
|
|
what is classically involved in secondary pulmonary tuberculosis?
|
apex of upper lobes of one or both lungs
|
|
|
is involvement of regional lymph nodes more prominent in primary TB or secondary TB?
|
primary
in secondary TB, bacilli elicit a prompt and marked tissue response that tends to wall off the focus of infection |
|
|
in which form of tuberculosis does cavitation occur readily?
|
secondary
cavitation is almost inevitable in neglected secondary TB, and erosion of the cavities into an airway is an important source of infection |
|
|
what is an important cause of infection (for other people) in people with secondary TB?
|
if untreated, cavities will erode into an airway and the person will cough sputum that contains the bacteria
|
|
|
how does secondary TB present?
|
may be asymptomatic
symptoms are usually insidious in onset: - malaise - anorexia - weight loss - fever (commonly low grade and remittent) - night sweats - increasing amounts of sputum (with progressive resp. involvement; first mucoid, later purulent; bloody in 50%) - pleuritic pain (extension of infection to pleural surfaces) |
|
|
how does the fever with secondary TB present?
|
low grade
remittent - appears late each afternoon and then subsides night sweats are common |
|
|
with what are systemic symptoms of secondary TB related?
|
cytokines released by activated macrophages
- TNF - IL-1 |
|
|
how is diagnosis of tuberculous pulmonary disease made?
|
combination of:
- history and physical - radiographic findings of consolidation/cavitation in apices of lungs - tubercle bacilli MUST be IDed -> acid-fast smears and cultures of sputum -> PCR amplification of DNA |
|
|
how do the tests for identification of tubercle bacilli compare to one another?
|
acid-fast smears - require 10,000 organisms for a positive test
cultures - conventional require 10 wks; liquid media require 2 wks; gold standard b/c allow for drug-susceptibility testing PCR - require <2wks; detect as few as 10 organisms |
|
|
why are all newly diagnosed cases of TB in the US treated with multiple drugs?
|
multidrug resistance is seen so commonly that all newly diagnosed cases are assumed to be resistant
|
|
|
what is the prognosis for tuberculosis?
|
good if infections are localized to the lungs, except when caused by drug-resistant strains or occur in aged, debilitate, or immunosuppressed individuals, who are at high risk of developing miliary tuberculosis
|
|
|
at what stages of HIV infection are patients at increased risk of tuberculosis?
|
all stages of HIV infection
|
|
|
how does HAART affect the risk of tuberculosis infection in HIV patients?
|
reduces the risk of tuberculosis infection, but even with HAART people infected with HIV are more likely to get tuberculosis than the uninfected
|
|
|
how does T-cell count affect the presentation of tuberculosis in HIV patients?
|
T cell counts >300 cells/mm^3 - usual secondary tuberculosis (apical disease with cavitation)
T cell counts <200 cells/mm^3 - clinical picture resembling primary tuberculosis |
|
|
what are the atypical features of tuberculosis in HIV-positive patients?
|
increased frequency of false-negative sputum smears and tuberculin tests (latter due to anergy)
absence of granulomas in tissues, particularly in the late stages of HIV |
|
|
where to inhaled M. tuberculosis bacilli typically implant?
|
distal airspaces of the lower part of the upper lobe or the upper part of the lower lobe, usually close to the pleura
|
|
|
what is a Ghon focus?
|
a 1- to 1.5-cm area of gray-white inflammation with consolidation caused by M. tuberculosis
in most cases the center of this focus will undergo caseating necrosis |
|
|
what is a Ghon complex?
|
combination of parenchymal lung lesion (gray-white inflammation with consolidation) and nodal involvement (caseation in lymph nodes draining the lung lesion) caused by M. tuberculosis infection
|
|
|
what happens to the Ghon complex after cell-mediated immunity has begun to control an M. tuberculosis infection?
|
undergoes progressivefibrosis, often followed by radiologically detectable calcification
|
|
|
what marks the sites of active tuberculosis involvement histologically?
|
characteristic granulomatous inflammatory reaction that forms both caseating and non-caseating tubercles
|
|
|
when can tubercles be seen macroscopically?
|
when multiple granulomas coalesce
individual tubercles are microscopic |
|
|
describe the focus of consolidation in secondary tuberculosis
|
a small focus of consolidation, less than 2cm in diameter, within 1-2cm of the apical pleura
sharply circumscribed, firm, gray-white to yellow areas that have a variable amount of central caseation and peripheral fibrosis |
|
|
what happens to the initial parenchymal focus of secondary tuberculosis?
|
undergoes progressive fibrous encapsulation, leaving only fibrocalcific scars
|
|
|
how does localized, apical, secondary pulmonary tuberculosis heal?
|
with fibrosis either spontaneously or after therapy
otherwise the disease progresses along several pathways |
|
|
what is progressive pulmonary tuberculosis?
|
apical lesion expands into adjacent lung and eventually erodes into bronchi and vessels
this evacuates the caseous center, creating a ragged, irregular cavity that is poorly walled off by fibrous tissue |
|
|
what is the result of erosion of blood vessels in progressive pulmonary tuberculosis?
|
hemoptysis
|
|
|
when does miliary pulmonary disease occur?
|
when M. tuberculosis organisms draining through lymphatics enter the venous blood and circulate back to the lung
|
|
|
describe the individual lesions of miliary tuberculosis
|
either microscopic or small, visible foci of yellow-white consolidation scattered through the lung parenchyma
may expand and coalesce resulting in consolidation of large regions or even whole lobes of the lung |
|
|
how do endobronchial, endotracheal, and laryngeal tuberculosis develop?
|
spread through lymphatic channels or from expectorated infectious material
mucosal lining may be studded with minute granulomatous lesions that may be apparent only microscopically |
|
|
when does systemic miliary tuberculosis occur?
|
when M. tuberculosis bacteremia disseminates through the systemic arterial system
|
|
|
where is miliary tuberculosis most prominent?
|
liver
bone marrow spleen adrenals meninges kidneys fallopian tubes epididymis **could involve any organ** |
|
|
what organs are commonly involved in isolated tuberculosis?
|
meninges (tuberculous meningitis)
kidneys (renal tuberculosis) adrenals (used to be an important cause of addison disease) bones (osteomyelitis) fallopian tubes (salpingitis) |
|
|
what is Pott disease?
|
a presentation of extrapulmonary tuberculosis that affects the spine, a kind of tuberculous arthritis of the intervertebral joints
|
|
|
how can Pott disease present with paraspinal "cold" abscesses?
|
paraspinal "cold" abscesses in these patients may track along tissue planes and present as an abdominal or pelvic mass
|
|
|
what is the most frequent presentation of extrapulmonary tuberculosis?
|
lymphadenitis
usually occurs in the cervical region (scrofula) |
|
|
what is a scrofula?
|
tuberculous infection of the lymph nodes in the neck
|
|
|
what is the difference between lymphadenitis in HIV-infected and uninfected people?
|
in infected individuals, lymphadenitis tends to be unifocal and localized
in individuals not infected, lymphadenitis is almost always multifocal, with systemic symptoms, and either pulmonary or other organ involvement |
|
|
how is intestinal tuberculosis contracted?
|
drinking of contaminated milk
|
|
|
in countries where milk is pasteurized, how is intestinal tuberculosis most commonly caused?
|
swallowing of coughed up infective material in patients with advanced pulmonary disease
|
|
|
how are M. tuberculosis organisms seeded in intestinal tuberculosis?
|
seeded to mucosal lymphoid aggregates of the small and large bowel
then undergo granulomatous inflammation that can lead to ulceration of the overlying mucosa, particularly in the ileum |
|
|
what is MAC (not membrane attack complex)?
|
Mycobacterium avium-intracellulare complex
M. avium and M. intracellulare are separate species, but the infections they cause are so similar that they are simply referred to as a complex |
|
|
where is MAC commonly found?
|
MAC = Mycobacterium avium-intracellulare complex
soil, water, dust, and domestic animals |
|
|
when is MAC infection common?
|
MAC = Mycobacterium avium-intracellulare complex
uncommon except among people with AIDS and low numbers of CD4+ lymphocytes (<60 cells/mm^3) |
|
|
what infection is caused by MAC in AIDS patients?
|
MAC = Mycobacterium avium-intracellulare complex
disseminated infections, and organisms proliferate abundantly in many organs, including lungs and GI system patients are feverish with drenching night sweats and weight loss |
|
|
what type of infection is caused by MAC in non-AIDS patients?
|
MAC = Mycobacterium avium-intracellulare complex
infection in non-AIDS patients is very rare primarily infects the lung, causing a productive cough and sometimes fever and weight loss |
|
|
what is the hallmark of MAC infections in patients with HIV?
|
MAC = Mycobacterium avium-intracellulare complex
abundant acid-fast bacilli within macrophages |
|
|
how does MAC infection appear macroscopically?
|
depending on the severity of immune deficiency, MAC infections can be widely disseminated throughout the mononuclear phagocyte system, causing enlargement of involved lymph nodes, liver, and spleen, or localized in the lungs
there may be a yellowish pigmentation to these organs secondary to the large number of organisms present in swollen macrophages granulomas, lymphocytes, and tissue destruction are rare |
|
|
what is Hansen's disease?
|
aka Leprosy
slowly progressive infection caused by Mycobacterium leprae mainly affects the skin and peripheral nerves and results in disabling deformities |
|
|
what is leprosy?
|
aka Hansen's disease
slowly progressive infection caused by Mycobacterium leprae mainly affects the skin and peripheral nerves and results in disabling deformities |
|
|
how is Mycobacterium leprae transmitted?
|
aerosolized respiratory droplets from asymptomatic lesions in the upper respiratory tract
|
|
|
how is M. leprae disseminated through the body?
|
inhaled and taken up by alveolar macrophages and disseminates through the blood
replicates only in relatively cool tissues of the skin and extremities |
|
|
where does M. leprae replicate?
|
cool tissues of the skin and extremities
|
|
|
what type of bacteria is Mycobacterium leprae?
|
weakly gram-positive bacillus (rod)
intracellular acid-fast aerobic |
|
|
in what animal does M. leprae propagate?
|
armadillo
it replicates best at 32-34 deg C (skin temperature and core temperature of armadillos) |
|
|
on what is the virulence of M. tuberculosis and M. leprae dependent?
|
properties of cell wall
|
|
|
how is cell-mediated immunity to M. leprae demonstrated?
|
delayed type (type IV) hypersensitivity reaction to dermal injections of a bacterial extract called lepromin
|
|
|
what are the two patterns of disease caused by Mycobacterium leprae?
|
tuberculoid leprosy (less severe form)
lepromatous leprosy (more severe form) |
|
|
how does tuberculoid leprosy present?
|
less severe form of leprosy
dry, scaly skin lesions that lack sensation often have asymmetric involvement of large peripheral nerves |
|
|
how does lepromatous leprosy present?
|
more severe form of leprosy
symmetric skin thickening and nodules aka anergic leprosy b/c of unresponsiveness of the host immune system |
|
|
what areas of the body are more severely affected with M. leprae?
|
cooler areas, including earlobes and feet
warmer areas, like axilla and groin are less severely affected |
|
|
what damages the peripheral nervous system in lepromatous leprosy?
|
widespread invasion of mycobacteria into Schwann cells and into endoneural and perineural macrophages
|
|
|
where can M. leprae be found in advanced cases of lepromatous leprosy?
|
in sputum and blood
|
|
|
what is borderline leprosy?
|
intermediate form of leprosy
|
|
|
what determines whether an individual has tuberculoid or lepromatous leprosy?
|
T-helper lymphocyte response to M. leprae
TH1 response - production of IL-2 and IFN-gamma - tuberculoid leprosy weak TH1 response/increased TH2 response - lepromatous leprosy |
|
|
what is the result of a weak TH1 response and an increased TH2 response in the case of leprosy?
|
causes lepromatous leprosy
causes weak cell-mediated immunity and an inability to control the bacteria |
|
|
when are antibodies to M. leprae antigens produced?
|
most commonly in lepromatous leprosy
|
|
|
what is the result of antibodies against M. leprae antigens?
|
paradoxically, these antibodies are usually not protective, but instead form immune complexes with free antigens
causes erythema nodosum, vasculitis, and glomerulonephritis |
|
|
how does tuberculoid leprosy present?
|
localized flat, red skin lesions that enlarge and develop irregular shapes with indurated, elevated, hyperpigmented margins and depressed pale centers (central healing)
nerves become enclosed within granulomatous inflammatory reactions and, if small, are destroyed (causes anesthesias and skin/muscle atrophy) |
|
|
what is the result of nerve degeneration in tuberculoid leprosy?
|
skin anesthesias and skin and muscle atrophy that render the person liable to trauma of the affected parts, leading to developmentent of chronic skin ulcers
contractures, paralyses, and autoamputation of fingers or toes may ensue |
|
|
what is caused by facial nerve involvement in tuberculoid leprosy?
|
paralysis of the eyelids, with keratitis and corneal ulcerations
|
|
|
what is seen on microscopic examination of all sites affected in tuberculoid leprosy?
|
granulomatous lesions closely resembling those in TB, and bacilli are almost never found
|
|
|
what is paucibacillary leprosy?
|
aka tuberculoid leprosy
granulomatous lesions and bacilli are almost never found |
|
|
what is indicated by the presence of granulomas and absence of bacteria in tuberculoid leprosy?
|
strong T-cell immunity
|
|
|
what is the prognosis for leprosy?
|
leprosy pursues an extremely slow course, spanning decades, so most patients die with leprosy rather than of it
|
|
|
how does lepromatous leprosy present?
|
macular, papular, or nodular lesions on the face, ears, wrists, elbows, and knees
with progression, the nodular lesions coalesce to yield a distinctive leonine facies involves skin, peripheral nerves, anterior chamber of the eye, upper airways (down to the larynx), testes, hands, and feet vital organs and CNS are rarely affected |
|
|
why are vital organs and CNS rarely affected with leprosy?
|
presumably because the core temperature is too high for growth of M. leprae
|
|
|
how do lepromatous lesions appear?
|
contain large aggregates of lipid-laden macrophages (lepra cells), often filled with masses (globi) of acid-fast bacilli
referred to as multibacillary leprosy because of the abundant bacteria |
|
|
how are lymph nodes and spleen affected in lepromatous leprosy?
|
contain aggregates of bacteria-filled foamy macrophages in the paracortical (T-cell) areas and reactive germinal centers
in advanced disease, aggregates of macrophages are present in the splenic red pulp and the liver |
|
|
what is the effect of lepromatous leprosy on the peripheral nerves?
|
especially on the ulnar and peroneal nerves where they approach the skin surface
they are symmetrically invaded with mycobacteria, with minimal inflammation |
|
|
what type of bacteria are spirochetes?
|
gram-negative, slender corkscrew-shaped bacteria
axial periplasmic flagella wound around a helical protoplasm |
|
|
what is outer sheath of spirochete bacteria?
|
membrane covering the bacteria
may mask bacterial antigens from host immune response |
|
|
what are the important spirochetes?
|
Treponema pallidum subspecies pallidum (syphilis)
Treponema pallidum subspecies pertenue (yaws) Treponema pallidum subspecies carateum (pinta) Borrelia burgdorferi (Lyme disease) Borrelia recurrentis (relapsing fever) |
|
|
what type of bacteria is Treponema pallidum?
|
gram-negative spirochete
microaerophile causes syphilis, yaws, and pinta depending on the subspecies |
|
|
what is Syphilis?
|
chronic venereal disease with multiple presentations, caused by Treponema pallidum subspecies pallidum
|
|
|
what techniques can be used to visualize Treponema pallidum?
|
silver stain
dark-field examination immunofluorescence Gram stain cannot be used because T. pallidum is too slender to be seen T. pallidum cannot be grown in culture |
|
|
how is T. pallidum transmitted?
|
sexual contact
transplacental transmission occurs readily, and active disease during pregnancy results in congenital syphilis |
|
|
what reduced the number of cases of syphilis in the US from the late 1940s until the 1970s?
|
public health programs
penicillin |
|
|
what are the three stages of syphilis and their main presenting features?
|
primary syphilis - single, firm, nontender, raised, red lesion (chancre)
secondary syphilis - skin lesions on the palms or soles of feet (may be maculopapular, scaly, or pustular tertiary syphilis - cardiovascular syphilis, neurosyphilis, and "benign tertiary syphilis" |
|
|
when does primary syphilis occur?
|
approximately 3 weeks after contact with an infected individual
|
|
|
what is primary syphilis?
|
single firm, nontender, raised, red lesion (chancre) located at the site of treponemal invasion on the penis, cervix, vaginal wall, or anus
occurs 3 weeks after infection heals in 3-6 weeks with/without therapy treponemes spread throughout the body by hematologic and lymphatic dissemination even before the appearance of the chancre |
|
|
how can T. pallidum be identified during primary syphilis?
|
spirochetes are plentiful within the chancre and can be seen by immunofluorescent stains of serous exudate
|
|
|
when does secondary syphilis occur?
|
approximately 2-10 weeks after the primary chancre
|
|
|
what is secondary syphilis?
|
skin lesions, which frequently occur on the palms or soles of feet, may be maculopapular, scaly, or pustular
caused by spread and proliferation of T. pallidum within skin and mucocutaneous tissues occurs 2-10 weeks after primary chancre heals after several weeks, after which pt enters the latent phase |
|
|
what is found on moist areas of the skin in patients with secondary syphilis?
|
condylomata lata - broad based, elevated plaques - contain spirochetes
moist areas are the anogenital region, inner thighs, and axillae |
|
|
what is found on any of the mucous membranes?
|
silvery-gray superficial erosions that contain spirochetes
particularly common in the mouth, pharynx, and external genitalia |
|
|
what lesions in secondary syphilis are infectious?
|
all of the painless superficial lesions contain spirochetes and so are infectious
maculopapular, scaly, or pustular skin lesions - condylomata lata - silvery-gray superficial erosions of mucous membranes |
|
|
in what percentage of people does secondary syphilis occur?
|
75% of untreated people
|
|
|
how common is tertiary syphilis?
|
rare where adequate medical care is available
occurs in approximately one third of untreated patients, usually after a latent period of 5 years or more |
|
|
what are the three main manifestations of tertiary syphilis?
|
cardiovascular syphilis
neurosyphilis benign tertiary syphilis **may occur alone or in combination** |
|
|
what is cardiovascular syphilis?
|
syphilitic aortitis leading to slowly progressive dilation of the aortic root and arch, causing aortic valve insufficiency and aneurysms of the proximal aorta
accounts for more than 80% of cases of tertiary syphilis |
|
|
what is neurosyphilis?
|
tertiary syphilis, where T. pallidum has invaded the CNS
may be symptomatic (2/3) or asymptomatic (1/3) symptomatic disease manifests as chronic meningovascular disease, tabes dorsalis, and a general paresis |
|
|
what is general paresis?
|
generalized brain parenchymal disease
impairment of mental function caused by damage to the brain from untreated (tertiary) syphilis |
|
|
how many cases of neurosyphilis cases does asymptomatic neurosyphilis account for?
|
1/3 cases of neurosyphilis
|
|
|
how is asymptomatic neurosyphilis diagnosed?
|
detected when a patient's CSF exhibits abnormalities such as pleocytosis, elevated protein levels, or decreased glucose levels
antibodies stimulated by spirochetes can be detected in CSF |
|
|
what is pleocytosis?
|
increased numbers of inflammatory cells
usually referring to an increase in white blood cell (WBC) count in a bodily fluid, such as cerebrospinal fluid (CSF) |
|
|
what is the most specific test for neurosyphilis?
|
anti-syphilis antibodies in the CSF
|
|
|
why is it important that patients with tertiary syphilis are tested for neurosyphilis even if they don't have neurologic symptoms?
|
antibiotics are given for a longer time if the spirochetes have spread to the CNS
|
|
|
what is benign tertiary syphilis?
|
formation of gummas in various sites, most commonly in bone, skin, and mucous membranes
may cause nodular lesions or, rarely, destructive, ulcerative lesions that mimic malignant neoplasms |
|
|
what are gummas?
|
nodular lesions probably related to the development of delayed hypersensitivity to Treponema pallidum
they occur most commonly in bone, skin, and the mucous membranes of the upper airway and mouth (any organ may be affected) now very rare because of the use of effective antibiotics and are seen mainly in individuals with AIDS |
|
|
what is caused by skeletal involvement in benign tertiary syphilis?
|
local pain
tenderness swelling sometimes pathologic fractures |
|
|
what is caused by skin and mucous membrane involvement in benign tertiary syphilis?
|
nodular lesions
destructive, ulcerative lesions that mimic malignant neoplasms (rare) |
|
|
what is congenital syphilis?
|
infection of fetus with T. pallidum via transplacental transmission
manifestations are divided into early and late, depending whether they occur in the first twoo years of life or later |
|
|
when does maternal transmission of Treponema pallidum happen most frequently?
|
during primary or secondary syphilis, when the spirochetes are most numerous
|
|
|
why is routine serologic testing for syphilis mandatory in all pregnancies?
|
manifestations of maternal syphilis may be subtle
intrauterine death and perinatal death each occurs in approximately 25% of cases of untreated congenital syphilis |
|
|
what are the divisions of congenital syphilis?
|
early (infantile) syphilis - occurs in first 2 years of life
late (tardive) syphilis - occurs later than first 2 years of life |
|
|
how is early congenital syphilis manifested?
|
nasal discharge and congestion in the first few months of life
desquamating or bullous rash can lead to sloughing of skin, particularly of hands and feet and around the mouth and anus hepatomegaly and skeletal abnormalities are also common |
|
|
how many untreated children with neonatal syphilis develop late manifestations?
|
nearly half
|
|
|
what is the mainstay of diagnosis for syphilis?
|
serology (nontreponemal antibody tests and antitreponemal antibody tests)
microscopy and PCR are useful |
|
|
what are nontreponemal antibody tests?
|
serologic tests for syphilis that measure antibody to cardiolipin, a phospholipidd present in both host tissues and T. pallidum
|
|
|
what antibodies are detected in the rapid plasma reagin test?
|
nontreponemal syphilis antibody
antibodies against cardiolipin, a phospholipid present in both host tissues and T. pallidum |
|
|
what antibodies are detected in the Venereal Disease Research Laboratory test?
|
aka VDRL test
nontreponemal syphilis antibody antibodies against cardiolipin, a phospholipid present in both host tissues and T. pallidum |
|
|
when do nontreponemal antibody tests become positive?
|
4-6 weeks after infection
nearly always positive in secondary syphilis, but usually become negative in tertiary syphilis immunofluorescence of exudate from the chancre is important for diagnosis early in infection |
|
|
how are the rapid plasma reagin and VDRL tests used?
|
screening tests for syphilis
monitor response to therapy (become negative after successful treatment of infection) |
|
|
with what are False-positive VDRL test results associated?
|
certain acute infections
collagen vascular diseases (SLE) drug addiction pregnancy hypergammaglobulinemia of any cause lepromatous leprosy |
|
|
what are the treponemal antibody tests?
|
measure antibodies that specifically react with T. pallidum
- fluorescent treponemal antibody absorption test - microhemagglutination assay for T. pallidum antibodies |
|
|
when do treponemal antibody tests become positive?
|
4-6 weeks after infection
remain positive indefinitely, even after successful treatment |
|
|
why are treponemal antibody tests not recommended as screening tests for syphilis?
|
they are significantly more expensive than nontreponemal tests
|
|
|
what is the effect of HIV infection on serologic response for syphilis?
|
may delay response, cause response to be absent, or exaggerate response (cause false-positive results)
tests remain useful in diagnosis and management of syphilis even in people infected with HIV |
|
|
what is a chancre?
|
a slightly elevated, firm, reddened papule, up to several centimeters in diameter, that erodes to create a clean-based shallow ulcer
contiguous ulcer creates a button-like mass directly adjacent to the eroded skin, providing the basis for the designation of hard chancre |
|
|
how do chancres appear on histologic examination?
|
treponemes are visible at the surface of the ulcer with silver stains or immunofluorescence techniques
contains an intense infiltrate of plasma cells, with scattered macrophages and lymphocytes and a proliferative endarteritis regional nodes are usually enlared due to nonspecific acute or chronic lymphadenitis, plasma cell-rich infiltrates, or granulomas |
|
|
when is endarteritis seen in syphilis?
|
all stages
starts with endothelial cell activation and proliferation and progresses to intimal fibrosis |
|
|
describe the morphology of secondary syphilis
|
widespread mucocutaneous lesions involve the oral cavity, palms of the hands, and soles of the feet
frequently consists of discrete red-brown macules less than 5mm in diameter, but it may be follicular, pustular, annular, or scaling red lesions in the mouth or vagina contain the most organisms and are the most infectious |
|
|
how do secondary syphilitic lesions appear histologically?
|
plasma cell infiltrate and obliterative endarteritis
less intense inflammation than primary chancre |
|
|
what organs are most frequently involved in tertiary syphilis?
|
aorta
CNS liver, bones, and testes |
|
|
what causes aortitis in tertiary syphilis?
|
endarteritis of the vasa vasorum of the proximal aorta
occlusion of the vasa vasorum results in scarring of the media of the proximal aortic wall, causing a loss of elasticity |
|
|
what is the result of aortitis in tertiary syphilis?
|
narrowing of the coronary artery ostia caused by subintimal scarring with resulting myocardial ischemia
|
|
|
what are the various forms of neurosyphilis?
|
meningovascular syphilis
tabes dorsalis general paresis |
|
|
what is the appearance of syphilitic gummas?
|
white-gray and rubbery
occur singly or multiply vary in size from microscopic lesions resembling tubercles to large tumor-like masses |
|
|
where do syphilitic gummas occur?
|
occur in most organs
common in skin, subcutaneous tissue, bone, and joints |
|
|
what is caused by gummas in the liver?
|
distinctive hepatic lesion known as hepar lobatum
|
|
|
how do gummas appear on histologic examination?
|
centers of coagulated, necrotic material and margins composed of plump, palisading macrophages and fibroblasts surrounded by large numbers of mononuclear leukocytes, chiefly plasma cells
treponemes are scant in gummas and are difficult to demonstrate |
|
|
what bones are affected by syphilitic osteochondritis and periostitis in congenital syphilis?
|
all bones
lesions of nose and lower legs are most distinctive |
|
|
what are the lesions of the nose caused by syphilitic osteochondritis and periostitis in congenital syphilis?
|
destruction of the vomer causes collapse of the bridge of the nose and later on the characteristic saddle nose deformity
|
|
|
what are the lesions of the lower leg caused by syphilitic periostitis of the tibia?
|
excessive new bone growth on the anterior surfaces and anterior bowing or saber shin
|
|
|
how is the liver affected in congenital syphilis?
|
diffuse fibrosis permeates lobules to isolate hepatic cells into small nests, accompanied by the characteristic lymphoplasmacytic infiltrate and vascular changes
gummas are occasionally found in the liver, even in early cases |
|
|
how are lungs affected in congenital syphilis?
|
diffuse interstitial fibrosis
in the syphilitic stillborn, the lungs appear pale and airless (pneumonia alba) |
|
|
what are the late manifestations (after 2 years) of congenital syphilis?
|
distinctive triad of interstitial keratitis, Hutchinson teeth, and eighth-nerve deafness
ocular changes include interstitial keratitis, choroiditis, and abnormal retinal pigmentation |
|
|
what is the triad of late manifestations of congenital syphilis?
|
interstitial keratitis
Hutchinson teeth eighth-nerve deafness |
|
|
what are Hutchinson teeth?
|
small incisors shaped like a screwdriver or a peg, often with notches in the enamel
|
|
|
when do eighth-nerve deafness and optic nerve atrophy occur in congenital syphilis?
|
develops secondarily to meningovascular syphilis
|
|
|
why has T. pallidum never been grown in culture?
|
doesn't have genes for making nucleotides, fatty acids, and most amino acids
|
|
|
when in syphilis does proliferative endarteritis occur?
|
all stages of syphilis
pathophysiology is not known, though scarcity of treponemes and intense inflammatory infitrate sggest that the immune response plays a role in the development of these lesions |
|
|
what type of T cells infiltrate the chancre of primary syphilis?
|
TH1 cells - activation of macrophages to kill bacteria may cause resolution of the local infection
|
|
|
what protects T. pallidum from antibodies?
|
outer membrane (either by the paucity of bacterial proteins in the membrane or absorption of the membrane by host proteins may play a role
|
|
|
is the immune response to T. pallidum adequate?
|
no - spirochetes disseminate, persist, and cause secondary and tertiary syphilis - if immune response was adequate, the spirochetes would be wiped out
|
|
|
what is the effect of antibiotic treatment of syphilis in patients with a high bacterial load?
|
massive release of endotoxins, resulting in a cytokine storm that manifests with high fever, rigors, hypotension, and leukopenia
|
|
|
what is the Jarisch-Herxheimer reaction?
|
in patients with a high bacterial load of spirochetes, treatment with antibiotics can cause a massive release of endotoxins, reesulting in a cytokine storm that manifests with high fever, rigors, hypotension, and leukopenia
commonly mistaken for drug allergy |
|
|
what is relapsing fever?
|
insect-transmitted disease characterized by recurrent fevers with spirochetemia
|
|
|
what causes epidemic relapsing fever?
|
body louse-transmitted Borrelia recurrentis, which infects only humans
|
|
|
what type of bacteria is Borrelia recurrentis?
|
gram-negative spirochete
|
|
|
what is Borrelia recurrentis associated with?
|
overcrowding due to poverty or war
caused multiple epidemics in Africa, Eastern Europe, and Russia in the first half of the twentieth century |
|
|
what causes endemic relapsing fever?
|
several Borrelia species, which are transmitted from small animals to humans by Ornithodorus (soft-bodied) ticks
|
|
|
how long is the incubation period in both louse- and tick-transmitted borreliosis?
|
1- to 2-weeks after the bite as the spirochetes multiply in the blood
|
|
|
how does clinical infection with Borrelia recurrentis manifest?
|
shaking chills
fever headache fatigue followed by DIC and multi-organ failure |
|
|
how are Borrelia spirochetes temporarily cleared from the blood?
|
anti-Borrelia antibodies, which target a single major surface protein called the variable major protein
|
|
|
why are Borrelia spirochetes only temporarily cleared from the blood?
|
cleared by anti-Borrelia antibodies, which target a single major surface protein called the variable major protein
after a few days, bacteria bearing a different surface antigen emerge and reach high densities in the blood (symptoms return until a second set of host antibodies clears the organisms) |
|
|
to what are the lessening severity of successive attacks of relapsing fever and its spontaneous cure attributed in untreated patients with Borrelia recurrentis infection?
|
limited genetic repertoire of Borrelia, enabling the host to build up cross-reactive as well as clone-specific antibodies
|
|
|
how is diagnosis of Borrelia recurrentis made?
|
identification of spirochetes in blood smears obtained during febrile periods
|
|
|
what happens to the spleen in fatal cases of louse-born Borrelia recurrentis?
|
moderately enlarged and contains focal necrosis and miliary collections of leukocytes, including neutrophils, and numerous borreliae
congestion and hypercellularity of the red pulp, which contains macrophages with phagocytosed red cells (erythrophagocytosis) |
|
|
what happens to the liver in fatal cases of louse-born Borrelia recurrentis?
|
enlarged and congested, with prominent Kupffer cells and septic foci
|
|
|
what is a frequent complication of Borrelia recurrentis infection?
|
aka relapsing fever
pulmonary bacterial superinfection |
|
|
for what is Lyme disease named?
|
Lyme, Connecticut, where there was an epidemic of arthritis associated with skin erythema in the mid-1970s
|
|
|
what bacteria causes Lyme disease?
|
Borrelia burgdorferi
transmitted from rodents to people by Ixodes deer ticks |
|
|
in what countries is Lyme disease common?
|
United States
Europe Japan |
|
|
where do most cases of Lyme disease occur in the United States?
|
Northeastern states
some parts of Midwestern states |
|
|
in endemic areas, what percentage of ticks are infected with Borrelia burgdorferi?
|
as many as 50%
may also be infected with Ehrlichia and Babesia |
|
|
what is the main method of diagnosis of Borrelia burgdorferi?
|
serology
PCR can be done on infected tissue |
|
|
what is stage 1 of Lyme disease?
|
spirochetes multiply and spread in the dermis at the site of a tick bite
causes an expanding area of redness, often with a pale center - called erythema chronicum migrans may be accompanied by fever and lymphadenopathy disappears in 4-12 weeks |
|
|
what is stage 2 of Lyme disease?
|
early disseminated stage
spirochetes spread hematogenously throughout the body and cause secondary skin lesions, lymphadenopathy, migratory joint and muscle pain, cardiac arrhythmias, and meningitis often associated with cranial nerve involvement |
|
|
what is stage 3 of Lyme disease?
|
late disseminated stage
occurs 2-3 years after the initial bite Lyme borreliae cause a chronic arthritis sometimes with severe damage to large joints and a polyneuropathy and encephalitis that vary from mild to debilitating |
|
|
what causes much of the pathology associated with Borrelia burgdorferi?
|
immune response against the bacteria and the inflammation that accompanies it
|
|
|
what stimulates the initial immune response in Borrelia burgdorferi infection?
|
binding of bacterial lipoproteins to TLR2 expressed by macrophages
in response, macrophages release proinflammatory cytokines (IL-6 and TNF) and generate bactericidal nitric oxide, reducing but usually not eliminating the infection |
|
|
how is the adaptive immune response to Lyme disease mediated?
|
CD4+ helper T cells and B cells
|
|
|
how does Borrelia burgdorferi escape the antibody response?
|
antigenic variation
|
|
|
what condition is caused by Borrelia hermsii?
|
endemic relapsing fever
caused by tick-bites |
|
|
describe the mechanism of antigenic variation of Borrelia burgdorferi
|
has a single promoter sequence and multiple coding sequences for an antigenic surface protein, V1sE, each of which can shuttle into position next to the promoter and be expressed
as antibody response to one V1sE protein is mounted, bacteria expressing an alternate V1sE protein can escape immune recognition |
|
|
what causes chronic manifestations of Lyme disease?
|
i.e. late arthritis
caused by immune response against persistent bacteria |
|
|
what is the morphology of skin lesions caused by Borrelia burgdorferi?
|
characterized by edema and a lymphocytic-plasma cell infiltrate
in early Lyme arthritis, the synovium resembles early rheumatoid arthritis, with villous hypertrophy, lining-cell hyperplasia, and abundant lymphocytes and plasma cells in the subsynovium |
|
|
what is the distinctive feature of Lyme arthritis?
|
an arteritis, which produces onionskin-like lesions resembling those seen in lupus
|
|
|
what is the result of Lyme meningitis?
|
CSF is hypercellular, due to a marked lymphoplasmacytic infiltrate, and contains anti-spirochete IgGs
|
|
|
what types of bacteria cause abscesses?
|
mixed anaerobic and facultative aerobic bacteria
|
|
|
what is the usual cause of abscesses?
|
commensal bacteria from adjacent sites (oropharynx, intestine, and female genital tract)
species found in the abscess reflects the normal flora |
|
|
what bacteria are represented by abscesses in the head and neck?
|
oral and pharyngeal flora
common anaerobes: - Prevotella (gram negative bacillus) - Porphyromonas (gram negative bacillus) facultative anaerobes: - S. aureus (gram positive) - S. pyogenes (gram positive) - Fusobacterium necrophorum |
|
|
what bacteria causes Lemierre syndrome?
|
infection of the lateral pharyngeal space and septic jugular vein thrombosis
caused by Fusobacterium necrophorum, an oral commensal bacteria |
|
|
what bacteria cause abdominal abscesses?
|
anaerobes of the GI tract
- Peptostreptococcus (gram-positive) - Clostridium spp. (gram-positive) - Bacteroides fragilis (gram-negative) - E. coli (gram-negative) |
|
|
what type of bacteria cause genital tract infections in women?
|
anaerobic gram-negative bacilli
- Prevotella spp. found in Bartholin cyst abscesses and tuboovarian abscesses - E. coli - Streptococcus agalactiae |
|
|
describe the morphology of abscesses caused by anaerobes
|
contain discolored and foul-smelling pus that is often poorly walled off
pathologically resemble lesions of common pyogenic infections gram stain reveals mixed infection with gram-positive and gram-negative rods and gram-positive cocci mixed with neutrophils |
|
|
what type of bacteria are Clostridium species?
|
gram-positive bacilli (rods)
anaerobic spore-producing present in the soil |
|
|
what conditions are caused by Clostridium perfringens?
|
cellulitis and myonecrosis of traumatic and surgical wounds (gas gangrene)
uterine myonecrosis associated with illegal abortions mild food poisoning infection of the small bowel associated with ischemia or neutropenia that often leads to severe sepsis |
|
|
what conditions are caused by Clostridium septicum?
|
cellulitis and myonecrosis of traumatic and surgical wounds (gas gangrene)
uterine myonecrosis associated with illegal abortions mild food poisoning infection of the small bowel associated with ischemia or neutropenia that often leads to severe sepsis |
|
|
what condition is caused by Clostridium tetani?
|
tetanus
|
|
|
what happens to Clostridium tetani in the body?
|
proliferates in puncture wounds and in the umbilical stump of newborn infants and releases a potent neurotoxin, called tetanospasmin, that causes convulsive contractions of skeletal muscles
|
|
|
what is tetanospasmin?
|
potent neurotoxin produced by Clostridium tetani, that causes convulsive contractions of skeletal muscles
|
|
|
what is tetanus toxoid?
|
formalin-fixed neurotoxin, part of the DPT (diphtheria, pertussis, and tetanus) immunization
decreased the incidence of tetanus worldwide |
|
|
with what is Clostridium botulinum associated?
|
grows in inadequately sterilized canned foods
releases a potent neurotoxin that blocks synaptic release of ACh and causes a severe paralysis of respiratory and skeletal muscles (botulism) |
|
|
with what is Clostridium difficile associated?
|
overgrows other intestinal flora in antibiotic-treated people
releases toxins causes pseudomembranous colitis |
|
|
how can clostridial infections be diagnosed?
|
culture (C. perfringens, C. septicum)
toxin assays (C. difficile) both (C. botulinum) |
|
|
why is tissue death essential for growth of C. perfringens in the host?
|
it cannot grow in the presence of oxygen
|
|
|
what are the virulence factors of C. perfringens?
|
collagenase
hyaluronidase 14 toxins (most importantly alpha-toxin) |
|
|
what is the most important exotoxin secreted by Clostridium perfringens?
|
alpha-toxin
phospholipase C activity that degrades lecithin - major component of cell membranes and destroys red cells, platelets, and muscle cells sphingomyelinase activity that contributes to nerve sheath damage |
|
|
what proteins produced by C. perfringens are important in bacterial invasiveness?
|
collagenase
hyaluronidase |
|
|
how is C. perfringens infection transmitted?
|
ingestion of contaminated food causes a brief diarrhea
spores, usually in contaminated meat, survive cooking and the organism proliferates in cooling food |
|
|
what is the function of C. perfringens enterotoxin?
|
forms pores in the epithelial cell membranes, lysing the cells and disrupting tight junctions between epithelial cells
|
|
|
how does botulism toxin act?
|
binds gangliosides on motor neurons and is transported into the cell
in th cytoplasm, the A fragment of botulism toxin cleaves a protein, called synaptobrevin, that mediates fusion of NT-containing vesicles with the neuron membrane blocking vesicle fusion, botulism toxin prevents the release of ACh at the neuromuscular junction, causing flaccid paralysis involvement of respiratory muscles leads to death |
|
|
hw does tetanus toxin act?
|
blocks release of gamma-aminobutyric acid, a NT that inhibits motor neurons
|
|
|
what is synaptobrevin?
|
protein that mediates fusion of NT-containing vesicles with the neuron membrane
cleaved by the A fragment of botulism toxin |
|
|
what toxins are produced by Clostridium difficile?
|
toxin A - enterotoxin that stimulates chemokine production and thus attracts leukocytes
toxin B - cytotoxin which causes distinctive cytopathic effects in cultured cells **both are glucosyl transferases and are part of a pathogenicity island that is absent from the chromosomes of nonpathogenic strains of C. difficile** |
|
|
how can clostridial cellulitis be differentiated from infection caused by pyogenic cocci?
|
foul odor
thin, discolored exudate relatively quick and wide tissue destruction on microscopic examination, amount of tissue necrosis is disporportionate to the number of neutrophils and gram-positive bacteria present |
|
|
how is clostridial cellulitis treated?
|
debridement and antibiotics
|
|
|
what are the characteristics of clostridial gas gangrene?
|
marked edema and enzymatic necrosis of involved muscle cells 1-3 days after injury
extensive fluid exudate, which is lacking in inflammatory cells, causes swelling of the affected region and the overlying skin, forming large, bullous vesicles that rupture gas bubbles caused by bacterial fermentation appear within the gangrenous tissues inflamed muscles become soft, blue-black, friable, and semi-fluid as a result of the massive proteolytic action of the released bacterial enzymes |
|
|
what bacterium is associated with dusk-colored, wedge-shaped infarcts in the small bowel, particularly in neutropenic people?
|
Clostridium perfringens
|
|
|
what obligate intracellular bacteria is unable to synthesize ATP at all?
|
Chlamydia trachomatis
|
|
|
what type of bacteria is Chlamydia trachomatis?
|
small, gram-negative
obligate intracellular parasite |
|
|
what are the two forms of Chlamydia trachomatis?
|
elementary body (EB) - infectious form; metabolically inactive, sporelike structure
reticulate body (RB) - metabolically active form; uses energy sources and amino acids from host cells; replicates and forms new elementary bodies |
|
|
how is the chlamydial elementary body taken up by host cells?
|
receptor-mediated endocytosis
|
|
|
what is the chlamydial elementary body?
|
infectious form; metabolically inactive, sporelike structure
taken up by host cells by receptor-mediated endocytosis prevent fusion of endosome and lysosome by an unknown mechanism |
|
|
what is the chlamydial reticulate body?
|
metabolically active form
uses energy sources and amino acids from the host cell replicates and ultimately forms new elementary bodies |
|
|
where does the chlamydial elementary body convert to the reticulate body?
|
inside the endosome
(after it is taken up into host cell via receptor-mediated endocytosis) |
|
|
what diseases are caused by C. trachomatis infection with serotypes D through K?
|
urogenital infections and inclusion conjunctivitis
|
|
|
what diseases are caused by C. trachomatis infection with serotypes L1, L2, and L3?
|
lymphogranuloma venereum
|
|
|
what diseases are caused by C. trachomatis infection with serotypes A, B, and C?
|
ocular infection of children, called trachoma
|
|
|
what is the most common sexually transmitted bacterial disease in the world?
|
Chlamydia trachomatis
|
|
|
what was the diagnosis of patients with C. trachomatis before C. trachomatis was identified?
|
non-gonococcal urethritis (NGU)
|
|
|
what is the cause of more than half the cases of non-gonococcal urethritis?
|
Chlamydia trachomatis
|
|
|
what are the current CDC recommendations for treatment of C. trachomatis?
|
treat both Neisseria gonorrhoeae and Chlamydia trachomatis in patients who are diagnosed with either infection, because co-infection with both is so common
|
|
|
what are the presentations of genital Chlamydia trachomatis infections?
|
epididymitis
prostatitis pelvic inflammatory disease pharyngitis conjunctivitis perihepatic inflammation proctitis |
|
|
how is Chlamydia trachomatis urethritis diagnosed?
|
culture of the bacteria in human cell lines
amplified nucleic acid tests performed on genital swabs or urine specimens are more sensitive and have supplanted cultures |
|
|
what is lymphogranuloma venereum?
|
a chronic, ulcerative disease
sporadic in the US and western Europe, but endemic in parts of Asia, Africa, the Caribbean region, and South America initially manifests as a small, often unnoticed, papule on the genital mucosa or nearby skin 2-6 weeks later, growth of the organism and the host response in draining lymph nodes produce swollen, tender lymph nodes, which may coalesce and rupture untreated, causes fibrosis and strictures in anogenital tract |
|
|
what type of strictures are particularly common in women with lymphogranuloma venereum?
|
rectal strictures
|
|
|
what is the morphology of lesions in lymphogranuloma venereum?
|
mixed granulomatous and neutrophilic inflammatory response
variable numbers of chlamydial inclusions are seen in the cytoplasm of epithelial cells or inflammatory cells regional lymphadenopath is common, usually occurring within 30 days of infection |
|
|
what characterizes lymph node involvement in lymphogranuloma venereum?
|
granulomatous inflammatory reaction associated with irregularly shaped foci of necrosis and neutrophilic infiltration
with time, the inflammatory reaction is dominated by nonspecific chronic inflammatory infiltrates and extensive fibrosis |
|
|
what kind of bacteria are Rickettsia spp.?
|
vector-borne obligate intracellular bacteria
gram-negative, rod-shaped |
|
|
what organism causes epidemic typhus?
|
Rickettsia prowazekii
gram negative rod |
|
|
what organism causes scrub typhus?
|
Orienta tsutusgamushi
gram negative rod rickettsia |
|
|
how is epidemic typhus transmitted? with what is it associated?
|
person to person transmission via body lice of Rickettsia prowazekii
associated with wars and human deprivation, when individuals are forced to live in close contact without changing clothes |
|
|
how is scrub typhus transmitted? with what is it associated?
|
transmission of Orienta tsutsugamushi by chiggers
associated with US soldiers in the Pacific in WWII and Vietnam |
|
|
how is Rocky Mountain spotted fever transmitted?
|
transmission of Rickettsia rickettsii to humans by dog ticks
usually transmitted after several hours of tick feeding or, less commonly, when the tick is crushed during removal from skin |
|
|
what organism causes Rocky Mountain spotted fever?
|
Rickettsia rickettsii
gram negative rod |
|
|
where is Rocky Mountain spotted fever most common?
|
southeastern and south-central United States
|
|
|
what cells are predominantly infected in Ehrlichiosis?
|
neutrophils (Anaplasma phagocytophilum and Ehrlichia ewingii)
macrophages (Ehrlichia chaffeensis) |
|
|
what are morulae?
|
characteristic cytoplasmic inclusions seen in leukocytes in Ehrlichiosis
occasionally shaped like mulberries composed of masses of bacteria |
|
|
how does Ehrlichiosis present?
|
abrupt onset of fever, headache, and malaise
may progress to respiratory insufficiency, renal failure, and shock rash is seen in about 40% of people with Ehrlichia chaffeensis infections |
|
|
what are the important Rickettsial infections?
|
Rickettsia prowazekii (epidemic typhus)
Orienta tsutsugamushi (scrub typhus) Rickettsia rickettsii (Rocky Mountain spotted fever) Anaplasma phagocytophilum (Ehrlichiosis) Ehrlichia ewingii (Ehrlichiosis) Ehrlichia chaffeensis (Ehrlichiosis) |
|
|
what cells are typically infected by Rickettsia prowazekii?
|
vascular endothelial cells, especially those in the lungs and brain
|
|
|
what cells are predominantly infected by Rickettsia rickettsii?
|
vascular endothelial cells, especially those in the lungs and brain
|
|
|
how does Rickettsia prowazekii enter endothelial cells? what happens once they are inside?
|
enter via endocytosis
escape from the endosome into the cytoplasm before formation of the acidic phagolysosome and then lyse the cell |
|
|
how does Rickettsia ricketsii enter endothelial cells? what happens once they are inside?
|
enter via endocytosis
escape from the endosome into the cytoplasm before formation of the acidic phagolysosome and then spread from cell to cell through actin-mobilized motion |
|
|
what is the primary cause of severe manifestations of rickettsial infection?
|
vascular leakage secondary to endothelial cell damage
causes hypovolemic shock with peripheral edema, as well as pulmonary edema, renal failure, and a variety of CNS manifestations including coma |
|
|
what part of the innate immune system mounts a response against rickettsial infection?
|
NK cells - produce IFN-gamma, reducing bacterial proliferation
subsequent CTL responses are critical for elimination of the rickettsial infection - lyse infected cells, reducing bacterial proliferation |
|
|
how are rickettsial infections diagnosed?
|
immunostaining of the organisms
detection of antirickettsial antibodies in the serum |
|
|
what are the gross changes in mild cases of typhus fver?
|
rash
small hemorrhages due to vascular lesions |
|
|
what are the gross changes in severe cases of typhus fever?
|
areas of necrosis of the skin and gangrene of the tips of the fingers, nose, earlobes, scrotum, penis, and vulva
irregular ecchymotic hemorhages may be found internally, principally in the brain, heart muscle, testes, serosal membrane, lungs, and kidneys |
|
|
what are the most prominent microscopic changes caused in typhus fever?
|
small-vessel lesions and focal areas of hemorrhage and inflammation in various organs and tissues
endothelial swelling in the capillaries, arterioles and venules, narrowing lumens cuff of mononuclear inflammatory cells usually surrounds affected vessels |
|
|
in the brain, what are characteristic typhus nodules composed of?
|
focal microglial proliferations with an infiltrate of mixed T lymphocytes and macrophages
|
|
|
how does scrub typhus compare to typhus fever?
|
milder
rash is usually transitory or might not appear at all vascular necrosis or thrombosis is rare, but there may be a prominent inflammatory lymphadenopathy |
|
|
how does Rocky Mountain spotted fever present?
|
a hemorrhagic rash that extends over the entire body, including the palms of the hands and soles of the feet
vascular lesions underlying rash often lead to acute necrosis, fibrin extravasation, and occasionally thrombosis of the small blood vessels, including arterioles in severe cases, foci of necrotic skin appear, particularly on the fingers, toes, elbows, ears, and scrotum |
|
|
what is the major cause of death in patients with Rocky Mountain spotted fever?
|
noncardiogenic pulmonary edema
|
|
|
what are fungi?
|
eukaryotes
|
|
|
what gives fungi their shape?
|
cell wall
|
|
|
what are the two forms that fungi can grow in?
|
molds - multicellular, threadlike filaments (hyphae) that grow and divide at the tips
yeasts - single cells or chains of cells - reproduce via budding |
|
|
how do most yeasts reproduce?
|
budding
|
|
|
what are pseudohyphae?
|
a chain of elongated yeast cells that forms when a yeast produces buds that fail to detach and instead become elongated
|
|
|
what are conidia?
|
round cells produced by molds that easily become airborne and disseminate the mold
|
|
|
dimorphic fungi
|
yeast in the heat (human body temp)
mold in the cold (room temp) |
|
|
how are fungal infections diagnosed?
|
histologic examination
culture is required for definitive ID of some species |
|
|
what are mycoses?
|
fungal infections
|
|
|
what are the four major types of mycoses (fungal infections)?
|
1) superficial and cutaneous
2) subcutaneous 3) endemic 4) opportunistic |
|
|
what are superficial/cutaneous mycoses?
|
limited to superficial or keratinized layes of skin, hair, and nails
|
|
|
what are subcutaneous mycoses?
|
involve skin, subcutaneous tissues, and lymphatics and rarely disseminate systemically
|
|
|
what are endemic mycoses?
|
caused by dimorphic fungi that can produce serious systemic illness in healthy individuals
|
|
|
what are opportunistic mycoses?
|
life-threatening systemic diseases in individuals who are immunosuppressed or who carry implanted prosthetic devices or vascular catheters
|
|
|
in what parts of the body are Candida species normal flora?
|
skin
mouth GI tract vagina |
|
|
what is the most frequent cause of human fungal infections?
|
C. albicans
|
|
|
how do most types of Candida infections originate?
|
when normal commensal flora breach the skin or mucosal barriers
|
|
|
what conditions are caused by Candida infection in otherwise healthy people?
|
vaginitis
diaper rash |
|
|
what patients are particularly susceptible to superficial candidiasis?
|
diabetics
burn patients |
|
|
in what patients is severe disseminated candidiasis most common?
|
patients with neutropenia due to leukemia, chemotherapy, or bone marrow transplantation
may cause shock and DIC |
|
|
how can a single strain of candida be successful as a commensal or as a pathogen?
|
shifts between different phenotypes in a reversible and apparently random fashion
involves coordinated regulation of phase-specific genes provides a way to adapt to changes in host environment, causing exhibition of altered colony morphology, cell shape, antigenicity, and virulence |
|
|
what are the three important adhesins produced by Candida?
|
1) integrin-like protein (binds residues on fibrinogen, fibronectin, and laminin)
2)protein that resembles transglutaminase substrates (binds to epithelial cells) 3) several agglutinins that bind to endothelial cells or fibronectin |
|
|
what enzymes are produced by candida to increase its invasiveness?
|
nine secreted aspartyl proteinases (degrade ECM proteins)
catalases (resist oxidative killing) |
|
|
how does Candida block neutrophil oxygen radical production and degranulation?
|
secretes adenosine
|
|
|
what are Candida biofilms?
|
microbial communities of C. albicans consisting of mixtures of yeast, filamentous forms, and fungal derived extracellular matrix
forms on implanted medical devices contributes to virulence because it reduces susceptibility of C. albicans to immune responses and antifungal drug therapy |
|
|
what is the first line of host defense against Candida?
|
oxidative killing by neutrophils and macrophages
|
|
|
what forms of Candida can escape from phagosomes, enter the cytoplasm and proliferate?
|
filamentous forms
NOT yeast forms |
|
|
what is the difference in T cell response elicited by yeast vs. mold forms of Candida?
|
yeast forms activated dendritic cells to produce IL-12 more, eliciting a protective antifungal TH1 response
mold forms stimulate a nonprotective TH2 response both elicit Th17 response, responsible for recruiting neutrophils and monocytes |
|
|
what T cell response is responsible for recruiting neutrophils and monocytes in fungal infections?
|
TH17 response
|
|
|
in what three forms can C. albicans appear in tissue sections?
|
yeastlike forms (blastoconidia)
pseudohyphae true hyphae (less common; defined by the presence of septae) |
|
|
what are C. albicans pseudohyphae?
|
important diagnostic clue
budding yeast cells joined end to end at constrictions |
|
|
what special fungal stains are used to better visualize C. albicans?
|
Gomori methenamine-silver
periodic acid-Schiff |
|
|
what is thrush?
|
superficial infection of C. albicans on mucosal surfaces of the oral cavity
|
|
|
how does thrush present?
|
gray-white, dirty-looking pseudomembranes composed of matted organisms and inflammatory debris
mucosal hyperemia and inflammation deep to the surface seen in newborns, debilitated people, children receiving oral steroids for asthma, and following a course of broad spectrum antibiotics, and HIV patients |
|
|
for what should people with oral thrush for no obvious reason be evaluated?
|
HIV infection
|
|
|
in what patients is candida esophagitis commonly seen?
|
AIDS patients
patients with hematolymphoid malignancies |
|
|
how does candida esophagitis present?
|
dysphagia (painful swallowing)
retrosternal pain white plaques and pseudomembranes on the esophageal mucosa (as seen via endoscopy) |
|
|
in what population is candida vaginitis common?
|
women who are diabetic, pregnant, or on oral contraceptive pills
|
|
|
how does candida vaginitis present?
|
vaginal itching
thick, curdlike vaginal discharge |
|
|
how can cutaneous candidiasis present?
|
infection of nail proper (onychomycosis)
infection of nail folds (paronychia) infection of hair follicles (folliculitis) infection of skin of armpits or webs of fingers and toes (intertrigo) infection of penile skin (balanitis) |
|
|
what is diaper rash?
|
cutaneous candidial infection in the perineum of infants, in the region of contact with wet diapers
|
|
|
what are the common patterns of invasive candidiasis?
|
1) renal abscesses
2) myocardial abcesses & endocarditis 3) brain microabscesses and meningitis 4) endophthalmitis (virtually any eye structure) 5) hepatic abscesses |
|
|
what causes invasive candidiasis?
|
blood-borne dissemination of C. albicans to various tissues or organs
fungus evokes little inflammatory reaction, causes the usual suppurative response, or produces granulomas |
|
|
what is the most common fungal endocarditis?
|
Candida endocarditis
usually occurs in the setting of prosthetic heart valves or in IV drug abusers |
|
|
what organism causes cryptococcosis?
|
Cryptococcus neoformans (fungus)
encapsulated yeast that causes meningoencephalitis in otherwise healthy individuals, but more frequently presents as opportunistic infection in pts. with AIDS, leukemia, lymphoma, SLE, or sarcoidosis |
|
|
what drug represents a major risk factor for infection with Cryptococcus neoformans?
|
high-dose corticosteroids
|
|
|
where is Cryptococcus neoformans found?
|
soil and pigeon droppings
infects on inhalation |
|
|
what are the virulence factors of C. neoformans that enable it to evade host defenses?
|
polysaccharide capsule
melanin production enzymes not very effective in individuals w/ intact immunity, but lead to disseminated disease in immunosuppressed individuals |
|
|
what is the principal capsular polysaccharide of C. neoformans?
|
glucuronoxylomannin
major virulence factor that inhibits phagocytosis by alveolar macrophages, leukocyte migration, and recruitment of inflammatory cells |
|
|
what is the effect of phenotypic switching in C. neoformans?
|
leads to changes in the structure and size of the capsule polysaccharide, providing a means to evade immune responses
|
|
|
what is laccase?
|
enzyme produced by Cryptococcus neoformans, that catalyzes the formation of a melanin-like pigment
helps in evasion of the immune response b/c of antioxidant properties |
|
|
describe the latency period of Cryptococcus neoformans
|
produces latent infections accompanied by granuloma formation that can reactivate in immunosuppressed hosts
|
|
|
what are the forms of Cryptococcus neoformans?
|
yeast form - encapsulated
NO hyphal or pseudohyphal forms |
|
|
what capsular polysaccharide stains are effective with Cryptococcus neoformans?
|
periodic acid-Schiff
mucicarmine stains intense red with both |
|
|
what is the effect of india ink preparation of Cryptococcus neoformans?
|
create a negative image
visualize the thick capsule as a clear halo within a dark background |
|
|
what is the primary site of Cryptococcus neoformans infection?
|
lungs
pulmonary involvement is usually mild and asymptomatic |
|
|
what lung lesions are seen in Cryptococcus neoformans infections?
|
solitary pulmonary granuloma, similar to the circumscribed (coin) lesion produced by Histoplasma
|
|
|
where are the major lesions of Cryptococcus neoformans located?
|
CNS, involving meninges, cortical gray matter, and basal nuclei
|
|
|
what is seen in the C. neoformans infected CNS in immunosuppressed patients?
|
virtually no inflammation
gelatinous masses of fungi grow in the meninges or expand the perivascular Virchow-Robin spaces within the gray matter (soap-bubble lesions) |
|
|
what are soap-bubble lesions?
|
expansions of the perivascular Virchow-Robin spaces within the gray matter of the brain
|
|
|
what are Virchow-Robin spaces?
|
aka enlarged perivascular spaces (EPVS)
spaces (often only potential) that surround blood vessels for a short distance as they enter the brain wall is formed by prolongations of the pia mater |
|
|
what is the effect of dissemination of C. neoformans in severely immunosuppressed persons?
|
dissemination to the skin, liver, spleen, adrenals, and bones
|
|
|
what fungus causes a rare granulomatous arteritis of the circle of Willis?
|
Cryptococcus neoformans
|
|
|
what is Aspergillus?
|
ubiquitous mold that causes allergic bronchopulmonary aspergillosis in otherwise healthy people, and causes serious sinusitus, pneumonia, and invasive disease in immunocompromised individuals
|
|
|
what are the major conditions that predispose a patient to Aspergillus infections?
|
neutropenia
corticosteroids |
|
|
what is the most common disease causing species of Aspergillus?
|
Aspergillus fumgatus
produces severe invasive infection in immunocompromised individuals |
|
|
how are Aspergillus spp. transmitted?
|
airborne conidia
small size of A. fumigatus spores enables them to reach alveoli |
|
|
what happens to Aspergillus conidia in the lung?
|
germinate into hyphae which then invade tissues
|
|
|
what is the major host defenses against Aspergillus?
|
neutrophils and macrophages
alveolar macrophages ingest and kill conidia neutrophils produce ROSs that kill hyphae |
|
|
what are the virulence factors produced by Aspergillus fumigatus?
|
adhesins (conidia bind to fibrinogen, laminin, complement, fibronectin, collagen, albumin, surfactant proteins)
antioxidants (melanin pigment, mannitol, catalases, superoxide dismutases) enzymes (phospholipases proteases) toxins (restrictocin and mitogillin) |
|
|
what are restrictocin and mitogillin?
|
ribotoxins produced by Aspergillus fumigatus that inhibit host-cell protein synthesis by degrading mRNAs
|
|
|
what is aflatoxin?
|
carcinogen produced by Aspergillus species growin on the surface of peanuts
may be a cause of liver cancer in Africa |
|
|
with what is Allergic bronchopulmonary aspergillosis associated?
|
hypersensitivity arising from superficial colonization of the bronchial mucosa
often occurs in asthmatics |
|
|
what is aspergilloma?
|
aka colonizing aspergillosis
growth of Aspergillus in pulmonary cavities (usually caused by prior tuberculosis, bronchiectasis, old infarcts, or abscesses) with minimal or no invasion of the tissues proliferating masses of hyphae form brownish fungal balls lying free within the cavities |
|
|
what is the common symptom of aspergilloma?
|
recurrent hemoptysis
|
|
|
what is invasive aspergillosis?
|
opportunistic infection confined to immunosuppressed hosts
primary lesion in lung and widespread hematogenous dissemination with involvement of heart valves and brain is common pulmonary lesions are necrotizing pneumonia with sharply delineated, rounded, gray foci and hemorrhagic borders (target lesions) |
|
|
describe the septate filaments of Aspergillus
|
5-10um thick
branch at acute angles (40deg) |
|
|
what is resembled by rhinocerebral Aspergillus infection in immunosuppressed individuals?
|
rhinocerebral zygomycosis (mucormycosis)
|
|
|
what is zygomycosis?
|
aka mucormycosis or phycomycosis
opportunistic infection caused by "bread mold fungi" (Mucor, Rhizopus, Absidia, and Cunninghamella) |
|
|
what are the "bread mold fungi"?
|
Mucor, Rhizopus, Absidia, and Cunninghamella
widely distributed fungi in nature belonging to the Zygomycetes class cause the opportunistic infection, zygomycosis |
|
|
what are the major predisposing factors for zygomycosis (mucormycosis)?
|
neutropenia
corticosteroid use diabetes mellitus iron overload burns, surgical wounds, trauma |
|
|
how are zygomycetes fungi transmitted?
|
airborne asexual spores
|
|
|
what are the most common infections caused by zygomycetes fungi?
|
infection in the sinuses and lungs
percutaneous exposure or ingestion can lead to infection |
|
|
what provides the initial defense against zygomycetes fungi?
|
macrophages (phagocytosis and oxidative killing of germinating spores)
neutrophils have key role in killing fungi during established infection |
|
|
what is the morphology of zygomycetes fungi?
|
nonseptate, irregularly wide fungal hyphae with frequent right-angle branching
readily demonstrable in necrotic tissues by H&E and fungal stains |
|
|
what are the three primary sites of infection by zygomycetes fungi?
|
nasal sinuses
lungs GI tract |
|
|
how does rhinocerebral mucormycosis arise?
|
zygomycetes fungi spread from nasal sinuses to the orbit and brain; they cause local tissue necrosis, invade arterial walls and penetrate the periorbital tissues and cranial vault; meningoencephalitis follows and possibly cerebral infarctions
occurs most commonly in diabetics |
|
|
what diseases are caused by Entamoeba histolytica?
|
amebic dysentery
liver abscess |
|
|
what diseases are caused by Balantidium coli?
|
colitis
|
|
|
what diseases are caused by Giardia lamblia?
|
diarrheal disease
malabsorption |
|
|
what diseases are caused by Isospora belli?
|
chronic enterocolitis
malabsorption |
|
|
what diseases are caused by Cryptosporidium spp.?
|
chronic enterocolitis
malabsorption |
|
|
what diseases are caused by Trichomonas vaginalis?
|
urethritis
vaginitis |
|
|
what diseases are caused by Naegleria fowleri?
|
meningoencephalitis
|
|
|
what diseases are caused by Acanthamoeba spp.?
|
meningoencephalitis
ophthalmitis |
|
|
what diseases are caused by plasmodium spp.?
|
malaria
|
|
|
what diseases are caused by Babesia microti?
|
babesiosis
|
|
|
what diseases are caused by Babesia bovis?
|
babesiosis
|
|
|
what diseases are caused by Trypanosoma brucei?
|
African sleeping sickness
|
|
|
what diseases are caused by Trypanosoma cruzi?
|
Chagas disease
|
|
|
what diseases are caused by Leishmania donovani?
|
Kala-azar
|
|
|
what diseases are caused by Leishmania spp.?
|
cutaneous and mucocutaneous leishmaniasis
|
|
|
what diseases are caused by Toxoplasma gondii?
|
toxoplasmosis
|
|
|
what are protozoa?
|
unicellular, eukaryotic organisms
|
|
|
how many people are affected and killed by malaria annually?
|
500 million affected
1 million people die each year |
|
|
according to WHO, where do 90% of malarial deaths occur?
|
sub-Saharan Africa
|
|
|
what is the leading cause of death in children younger than 5 years old in sub-Saharan Africa?
|
malaria
|
|
|
what are the four malaria parasites that infect humans?
|
Plasmodium falciparum
Plasmodium vivax Plasmodium ovale Plasmodium malariae |
|
|
how are the malarial parasites transmitted?
|
female Anopheles mosquitoes that are widely distributed throughout Africa, Asia, and Latin America
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|
in what population do nearly all of the 1500 new cases of malaria each year in the US occur?
|
travelers
immigrants rare cases transmitted by Anopheles mosquitoes or blood transfusion do ocur |
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what was the effect of worldwide public health efforts to control malaria in the 1950s through 1980s?
|
mosquitoes became resistant to DDT and malathion
Plasmodium spp. became resistant to chloroquine and pyrimethamine |
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what malarial parasite causes severe malaria?
|
Plasmodium falciparum
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what is caused by Plasmodium vivax?
|
malaria
low levels of parasitemia, mild anemia, and, in rare instances, splenic rupture and nephrotic syndrome |
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what is caused by Plasmodium ovale?
|
malaria
low levels of parasitemia, mild anemia, and, in rare instances, splenic rupture and nephrotic syndrome |
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what is caused by Plasmodium malariae?
|
malaria
low levels of parasitemia, mild anemia, and, in rare instances, splenic rupture and nephrotic syndrome |
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what is caused by Plasmodium falciparum?
|
severe malaria
high levels of parasitemia, severe anemia, cerebral symptoms, renal failure, pulmonary edema, and death |
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|
what is the infectious stage of malarial parasites? where is it found?
|
sporozoite
found in salivary glands of female Anopheles mosquitoes |
|
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how are Plasmodium spp. transmitted?
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sporozoites (infectious form) are found in female Anopheles mosquito salivary glands
mosquito takes blood meal and releases sporozoites into human's blood within minutes, sporozoites attach to and invade liver cells |
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to what do Plasmodium spp. bind in order to invade liver cells?
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hepatocyte receptor for serum proteins, thrombospondin and properdin
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what are merozoites?
|
asexual, haploid forms of plasmodium spp. produced in liver cells
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what are hypnozoites?
|
latent form of Plasmodium vivax and Plasmodium ovale in hepatocytes
cause relapses of malaria long after initial infection |
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which plasmodium species are capable of forming latent infection of hepatocytes?
|
Plasmodium vivax
Plasmodium ovale |
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|
what happens to malarial parasites inside of hepatocytes?
|
multiply rapidly, releasing as many as 30,000 merozoites (asexual, haploid forms) when each infected hepatocyte ruptures
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what happens to malarial parasites after they've been released from hepatocytes?
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merozoites bind to sialic acid residues on glycophorin molecules on the surface of red cells, via a parasite lectin-like molecule
they are then endocytosed |
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|
what happens to plasmodium parasites in red blood cells?
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grow in a membrane-bound digestive vacuole, hydrolyzing hemoglobin through secreted enzymes (go from trophozoite -> schizont -> merozoite or gametocyte)
red cell is lysedreleasing new merozoites and gametocytes |
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what is a trophozoite?
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first stage of malarial parasites in the red cell
defined by the presence of a single chromatin mass |
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what is a schizont?
|
second stage of malarial parasites in the red cell
has multiple chromatin masses, each of which develops into a merozoite |
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what form of plasmodium infects female Anopheles mosquitoes when they take a blood meal from a malaria patient?
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gametocyte
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what are the features of Plasmodium falciparum that account for its greater pathogenicity?
|
1) infects red blood cells of any age (other species can only infect either young or old red cells)
2) causes infected red cells to clump and stick to endothelial cells lining small blood vessels, blocking blood flow 3) stimulates production of high levels of cytokines (TNF, IFN-gamma, IL-1) |
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what is the result of the ability of P. falciparum to infect RBCs of any age?
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leads to high parasite burdens and profound anemia
other species infect only either young or old red cells, which makes a smaller fraction of the red cell pool |
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how does P. falciparum cause blockage of blood flow?
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P. falciparum erythrocyte membrane protein 1 (PfEMP1) forms knobs on the surface of red cells and binds to ligands on endothelial cells (CD36, thrombospondin, VCAM-1, ICAM-1, and E-selectin) in small vessels and causes a blockage
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what is the rosette formed by P. falciparum?
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clump of red blood cells
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what is PfEMP1?
|
P. falciparum erythrocyte membrane protein 1
protein that is expressed on infected red blood cells that forms knobs on the surface binds to ligands on endothelial cells (CD36, thrombospondin, VCAM-1, ICAM-1, E-selectin) and causes blockage of blood flow in small vessels |
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to what ligands on small vessel endothelial cells does PfEMP1 bind?
|
PfEMP1 = P. falciparum erythrocyte membrane protein 1
binds to CD36, thrombospondin, VCAM-1, ICAM-1, and E-selectin |
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|
what is the leading cause of death in malaria-infected children?
|
cerebral symptoms caused by ischemia due to poor perfusion as a result of red blood cell sequestration in small vessels
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what is the effect of stimulation of production of high levels of cytokines by P. falciparum?
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cytokines suppress production of red blood cells, increase fever, stimulate NO production (leads to tissue damage), and induce expression of endothelial receptors for PfEMP1 (increases sequestration of RBCs in small blood vessels)
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how does P. falciparum stimulate the production of high levels of cytokines?
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GPI-linked proteins including merozoite surface antigens are released from infected red cells, which induces cytokine production by host cells
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what are the two general mechanisms of host resistance to Plasmodium?
|
inherited alterations in red cells
repeated or prolonged exposure to plasmodium species causes reduced severity of illness |
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how does sickle cell relate to malaria?
|
heterozygotes with the sickle cell trait are resistant to malaria; they can be infected with P. falciparum, but they are less likely to die from infection b/c the HbS trait causes the parasites to grow poorly or die due to the low [O2]
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what are the red blood cell alterations that render a person resistant to Plasmodium?
|
HbS
HbC loss of Duffy blood group antigen |
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how does Plasmodium vivax enter red cells?
|
binds to the Duffy blood group antigen
many Africans, including most Gambians, are not susceptible to infection by P. vivax because they do not have the Duffy blood group antigen |
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how does P. falciparum escape antibody responses to PfEMP1?
|
PfEMP1 = P. falciparum erythrocyte membrane protein 1
antigenic variation each haploid (merozoite) P. falciparum genome has about 50 var genes, each encoding a variant of PfEMP1 at least 2% of parasites switch PfEMP1 genese each generation |
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what is caused initially by P. falciparum infection?
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congestion and enlargement of the spleen
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what is the basis of the diagnostic test for P. falciparum infection?
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parasites are present within red cells
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what happens to the spleen in chronic malaria infection?
|
becomes increasingly fibrotic and brittle, with a thick capsule and fibrous trabeculae
gray or black parenchyma because of phagocytic cells containing granular brown-black, faintly birefringent hemozoin pigment numerous macrophages with engulfed parasites, RBCs and debris |
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how is the liver affected by progressive malaria?
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progressively enlarged and pigmented
Kupffer cells are heavily laden with malarial pigment, parasites, and cellular debris some pigment is also found in parenchymal cells |
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what organism causes malignant cerebral malaria?
|
Plasmodium falciparum
|
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what happens in malignant cerebral malaria?
|
brain vessels are plugged with parasitized red cells
ring hemorrhages around the vessels, probably related to local hypoxia incident to the vascular stasis and small inflammatory reactions more severe hypoxia -> degeneration of neurons, focal ischemic softening, and occasionally scant inflammatory infiltrates in the meninges |
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what are Durck granulomas?
|
aka malarial granuloma
focal inflammatory reactions to the vascular stasis caused by P. falciparum |
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|
what are the cardiac effects of Plasmodium spp?
|
nonspecific focal hypoxic lesions may be induced by progressive anemia and circulatory stasis in chronically infected people
focal interstitial infiltrates pulmonary edema or shock with DIC -> death in nonimmune patients (sometimes happens in the absence of other characteristic lesions) |
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what are are Babesia microti and Babesia divergens?
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malaria-like protozoans
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how is Babesia microti transmitted?
|
deer ticks (same ones that carry Lyme disease and granulocytic ehrlichiosis)
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how is Babesia divergens transmitted?
|
deer ticks (same ones that carry Lyme disease and granulocytic ehrlichiosis)
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what is the reservoir for Babesia microti?
|
B. microti is a protozoan
reservoir is white-footed mouse; in some areas, all mice have a persistent low-level parasitemia |
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|
how is the protozoan, Babesia microti, transmitted iatrogenically?
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survives well in refrigerated blood, so transfusion-acquired babesiosis has been reported
**not a huge means of transmission** |
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what is the effect of Babesiae protozoans in the body?
|
parasitize red blood cells
cause fever and hemolytic anemia symptoms are mild except in debilitated or splenectomized individuals who develop severe and fatal parasitemias |
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|
for what organism are Maltese crosses diagnostic?
|
Maltese crosses are the characteristic tetrads of Babesiae (microti and divergens) in red blood cells
cross-shaped inclusions formed by 4 merozoites asexually budding but attached together forming a structure looking like a "Maltese Cross" |
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what are the findings in fatal cases of Babesia microti parasitemia?
|
jaundice
hepatic necrosis acute renal tubular necrosis adult respiratory distress syndrome erythrophagocytosis visceral hemorrhages |
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how is Leishmaniasis transmitted?
|
bites of infected sandflies
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where is Leishmaniasis endemic?
|
throughout the Middle East, South Asia, Africa, and Latin America
epidemic in Sudan, India, Bangladesh, and Brazil |
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|
what conditions exacerbate Leishmaniasis?
|
conditions that interfere with T-cell function (AIDS)
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how is Leishmaniasis diagnosed?
|
culture or histologic examination
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|
what organism causes Leishmaniasis?
|
either Leishmania donovani or Leishmania chagasi
kinetoplast-containing protozoan parasites |
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|
what type of organisms are Leishmania?
|
obligate intracellular, kinetoplast-containing protozoan parasites
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|
what are the two forms in the life cycle of Leishmania?
|
promastigote - develops and lives extracellularly in the sandfly vector
amastigote - multiplies intracellularly in host macrophages |
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|
what is the reservoir for Leishmania?
|
mammals (rodents, dogs, and foxes)
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how do Leishmania infect sandflies?
|
when a sandfly bites an infected human or animal, macrophages harboring the amastigotes are ingested
amastigotes differentiate into promastigotes promastigotes multiply within the digestive tract of the sandfly and migrate to the salivary gland, where they wait until the sandfly's next blood meal |
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|
how do Leishmania infect people?
|
slender, flagellated infectious promastigotes are released from the salivary glands into the host dermis along with the sandfly saliva, which potentiates parasite infectivity
promastigotes are phagocytosed by macrophages, and the acidity in the phagolysosome induces differentiation into round amastigotes amastigotes proliferate within macrophages and dying macrophages release progeny amastigotes that can infect additional macrophages |
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what is the structure of Leishmania amastigotes?
|
round, lacking a flagella
contain a single mitochondrion with its DNA massed into a unique sub-organelle (kinetoplast) |
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what is a kinetoplast?
|
a sub-organelle within a mitochondrion, that contains the massed mitochondrial DNA
found in Leishmania species as well as African trypanosomes |
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|
what organisms cause cutaneous leishmaniasis?
|
Leishmania major and Leishmania tropica in the old world
Leishmania mexicana and Leishmania braziliensis in the New World |
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|
what is espundia?
|
aka mucocutaneous leishmaniasis
disease caused by Leishmania braziliensis in the New World |
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|
what organisms cause visceral leishmaniasis?
|
Leishmania donovani and Leishmania infantum in the Old World
Leishmania chagasi in the New World **intracellular protozoans** |
|
|
what determines the tropism of Leishmania species?
|
optimal temperature for thir growth
parasites that cause visceral disease grow best at 37degC parasites that cause cutaneous disease grow better at lower temps **cutaneous leishmania are viscerotropic in HIV patients** |
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|
what two abundant surface glycoconjugates are important for the virulence of Leishmania promastigotes?
|
lipophosphoglycan - forms dense glycocalyx - activates complement and inhibits MAC deposition on parasite surface
gp63 - cleaves complement and some lysosomal antimicrobial enzymes - binds fibronectin receptors on macrophages |
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|
what is lipophosphoglycan?
|
abundant surface glycoconjugate produced by Leishmania promastigotes
forms a dense glycocalyx that both activates complement (causing opsonization of the parasite) and inhibits complement action (prevents membrane attack complex insertion) protects parasites in phagolysosomes by scavenging oxygen radical and by inhibiting lysosomal enzymes |
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|
what is gp63?
|
zinc-dependent proteinase
cleaves complement and some lysosomal antimicrobial enzymes binds fibronectin receptors on macrophages and promotes promastigote adhesion to macrophages |
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|
how do Leishmania amastigotes protect themselves from the low pH of the phagolysosomes in which they reproduce?
|
express a proton-transporting ATPase, which maintains the intracellular parasite pH at 6.5
phagolysosome pH = 4.5 |
|
|
what part of the immune system is needed to control Leishmania protozoans?
|
parasite-specific CD4+ helper T lymphocytes of the TH1 subset
|
|
|
how do Leishmania evade host immunity?
|
alter macrophage gene expression and impair the development of the TH1 response
|
|
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how does the T cell response affect the infectivity of Leishmania?
|
high levels of TH1-derivd IFN-gamma activates macrophages to kill Leishmania protozoans through reactie oxygen species
dominant TH2 response (IL-4, IL-13, and IL-10) preents effective killing of the protozoans by inhibiting the microbicidal activity of macrophages |
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|
what are the characteristics of visceral leishmaniasis?
|
hepatosplenomegaly
lymphadenopathy pancytopenia fever weight loss |
|
|
what disease is called kala-azar?
|
kala-azar is the Urdu word for black fever (Urdu is the language spoken in India and Pakistan)
it is used to describe visceral leishmaniasis because this disease results in hyperpigmentation of the skin in individuals of South Asian ancestry |
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|
what is the usual cause of death in patients infected with visceral leishmaniasis?
|
secondary bacterial infections, to which they are predisposed becayse of the overloading of phagocytic cells with parasites
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|
what is cutaneous leishmaniasis?
|
relatively mild, localized disease consisting of ulcer(s) on exposed skin
lesion begins as a papule surrounded by induration, changes into a shallow, slowly expanding ulcer (often with heaped up borders), and usually heals by involution within 6-18 months without Tx |
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what is mucocutaneous leishmaniasis?
|
ulcerating or non-ulcerating lesions, which may be disfiguring, develop in nasopharyngeal areas
lesions may be progressive and highly destructive eventually, the lesions remit and scar, although reactivation may occur after long intervals |
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|
what is diffuse cutaneous leishmaniasis?
|
rare form of dermal infection, thus far found in Ethiopia and adjacent East Africa, as well as in Central and South America
begins as a single skin nodule, which continues spreading until the entire body is covered by nodular lesions |
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|
in what leishmania lesions can the protozoans be found microscopically?
|
visceral - overloaded in phagocytic cells
cutaneous - few parasites mucocutaneous - initially high numbers, which decline as inflammatory response becomes granulomatous diffuse cutaneous - lesions contain aggregates of foamy macrophages stuffed with leishmania |
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|
what are African trypanosomes?
|
kinetoplastid parasites that proliferate as extracellular forms in the blood
cause sustained or intermittent fevers, lymphadenopathy, splenomegaly, progressive brain dysfunction, cachexia, and death |
|
|
what type of infections are caused by Trypanosoma brucei rhodesiense?
|
acute and virulent infections
occur in East Africa |
|
|
what type of infections are caused by Trypanosoma brucei gambiense?
|
chronic infections
occurs most frequently in the West African bush |
|
|
what vector is responsible for transmitting African Trypanosomas?
|
Tsetse flies (genus Glossina)
|
|
|
what is the reservoir for Trypanosoma brucei rhodesiense?
|
wild and domestic animals
|
|
|
how do Trypanosoma protozoans replicate in the Tsetse fly?
|
multiply in the stomach and in the salivary glands before developing into nondividing trypomastigotes
|
|
|
what form of Trypanosoma protozoans are transmitted from the Tsetse fly to humans?
|
trypomastigotes (nondividing form)
|
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what is the variant surface glycoprotein (VSG) of African trypanosomes?
|
the single, abundant, glycolipid-anchored protein that covers the trypanosome protozoans
becomes antigen for host antibodies as the protozoans proliferate and allows phagocytes to kill most of the organisms, causing a spike of fever a small number of parasites undergo a genetic rearrangement and produce a different VSG on their surface and so escape the host immune response process repeats |
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|
what causes the recurrent spikes of fever in infection with African trypanosomes?
|
host produces antibodies to variant surface glycoprotein (VSG) of the trypanosomes, causing phagocytosis and destruction of most of the organisms, causing the fever
the fever recurs because a few parasites undergo a genetic rearrangment producing a different VSG and escape the immune response the process repeats |
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|
how does African trypanosomiasis present?
|
large, red, rubbery chancre forms at the site of Tsetse fly bite (large numbers of parasites surrounded by a dense, mostly mononuclear, inflammatory infiltrate)
waves of fever before finally causing meningitis |
|
|
how is expression of variant surface glycoprotein (VSG) regulated by Trypanosome protozoans?
|
Trypanosomes have many VSG genes scattered throughout the genome
only the one gene found within bloodstream expression sites (in telomeres) is expressed new VSG genes move into the bloodstream expression sites mainly by homologous recombination |
|
|
what is the result of chronicity in Trypanosome infection?
|
lymph nodes and spleen enlarge due to infiltration by lymphocytes, plasma cells, and macrophages (filled with dead parasites)
|
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|
where do Trypanosomes tend to concentrate?
|
capillary loops such as the choroid plexus and glomeruli
|
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what are the CNS effects when Trypanosomes breach the blood-brain barrier?
|
leptomeningitis that extends into perivascular Virchow-Robin spaces
eventually, a demyelinating panencephalitis occurs |
|
|
what are Mott cells?
|
plasma cells containing cytoplasmic globules filled with immunoglobulins
|
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|
what organism causes American trypanosomiasis?
|
aka Chagas disease
Trypanosoma cruzi |
|
|
what type of organism is Trypanosoma cruzi?
|
kinetoplastid, intracellular protozoan parasite
causes American trypanosomiasis (Chagas disease) |
|
|
where does Chagas disease occur?
|
aka American trypanosomiasis
rarely in US and Mexico, but more common in South America, particularly Brazil |
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|
what are the reservoirs for Trypanosoma cruzi?
|
cats
dogs rodents |
|
|
how is Trypanosoma cruzi transmitted?
|
from animal to human by "kissing bugs" (triatomids)
kissing bugs hide in the cracks of loosely constructed houses, feed on sleeping inhabitants, and pass protozoans in feces protozoans enter the host through damaged skin or through mucous membranes |
|
|
what is a chagoma?
|
transient, erythematous nodule at the site of skin entry of Trypanosoma cruzi
|
|
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what is required to stimulate the development of amastigotes of Trypanosoma cruzi?
|
brief exposure to acidic environment of phagolysosome
T. cruzi gains exposure to lysosomes by stimulating an increase in [Ca]cytoplasmic in host cells, which promotes fusion of the phagosome and lysosome |
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|
what is the intracellular stage of Trypanosoma cruzi?
|
amastigote stage
|
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|
why is the low pH of the lysosome important for T. cruzi?
|
stimulates amastigote development
activates pore-forming proteins that disrupt lysosomal membrane, releasing protozoan into cytoplasm |
|
|
what is the life cycle of T. cruzi in humans?
|
trypomastigotes passed from "kissing bugs" in the feces and enter host through damaged skin or through mucous membranes
phagocytosed by macrophages stimulates fusion of phagosome with lysosome low pH stimulates development of amastigotes as well as activation of pore-forming proteins reproduce as rounded amastigotes in cytoplasm develop flagella lyse host cells, enter blood stream, penetrate smooth, skeletal, and cardiac muscles |
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|
what is acute Chagas disease?
|
mild infection with T. cruzi
cardiac damage results from direct invasion of myocardial cells by organisms and subsequent inflammation rarely presents w/ high parasitemia, fever, or progressive cardiac dilation/failure often presents with generalized lymphadenopathy or splenomegaly |
|
|
what cells are preferentially infected with Trypanosoma cruzi?
|
macrophages
smooth muscle skeletal muscle cardiac muscle |
|
|
what is chronic Chagas disease?
|
cardiac and digestive tract damage caused by immune response induced by T. cruzi protozoans (present in small numbers)
damage to myocardial cells and to conductance pathways results in dilated cardiomyopathy and cardiac arrhythmias damage to myenteric plexus causes dilation of colon and esophagus occurs in 20% of people 5-15 years after Trypanosoma cruzi infection |
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what is megacolon?
|
dilation of the colon
|
|
|
what are metazoa?
|
multicellular, eukaryotic organisms
in a broad sense, refers to all animals related to microbiology, refers to parasitic worms |
|
|
where is Strongyloides stercoralis endemic?
|
southeastern United States
South America sub-Saharan Africa Southeast Asia |
|
|
how does Strongyloides stercoralis infect humans?
|
live in soil and infect humans when larvae penetrate the skin, travel in circulation to the lungs, travel up trachea, and are swallowed
female worms reside in the small intestinal mucosa, where they produce eggs by asexual reproduction most larvae are passed in the stool and then may contaminate soil to continue cycle |
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|
what are the symptoms of Strongyloides stercoralis in immunocompetent hosts?
|
diarrhea, bloating, and occasionally malabsorption
|
|
|
what happens when Strongyloides stercoralis larvae hatched in the gut invade the colon mucosa?
|
reinitiate infection (autoinfection)
|
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|
what patients exhibit very high worm burdens with Strongyloides stercoralis, as the result of uncontrolled autoinfection?
|
immunocompromised hosts, especially those people on prolonged corticosteroid therapy
|
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|
how does sepsis accompany the hyperinfection of immunocompromised persons with Strongyloides stercoralis?
|
bacteria from the intestine are carried into the host's blood by the invading larvae
|
|
|
what is seen in mild strongyloidiasis?
|
Strongyloides stercoralis worms, mainly larvae, are present in the duodenal crypts but are not seen in underlying tissue
eosinophil-rich infiltrate in lamina propria with mucosal edema |
|
|
where can adult worms, larvae, and eggs of Strongyloides stercoralis be found in hyperinfection?
|
crypts of duodenum and ileum
skin lungs sputum |
|
|
what organism causes cysticercosis?
|
Taenia solium
cestode (tapeworm) |
|
|
what organism causes hydatid disease?
|
Echinococcus granulosus
cestode (tapeworm) |
|
|
what are the two mammalian hosts required by tapeworms (cestodes)?
|
definitive host - host in which worms reach sexual maturity
intermediate host - worm does not reach sexual maturity |
|
|
what do Taenia solium tapeworms consist of?
|
head (scolex) that has suckers and hooklets that attach to the intestinal wall
neck many flat segments called proglottids (contain both male and female reproductive organs) |
|
|
where do new proglottids form in Taenia solium tapeworms?
|
behind the scolex
the most distal proglottids are mature and contain many eggs (they can detach and be shed in the feces) |
|
|
what are the two ways by which Taenia solium can be transmitted to humans?
|
ingestion of undercooked pork, containing larval cysts (cysticerci) - adult tapeworms develop in intestine can grow to great lengths and produce mild abdominal Sx
ingestion of eggs in food or water contaminated with human feces by intermediate host - larvae hatch, penetrate the gut wall, disseminate hematogenously, and encyst in many organs |
|
|
what is caused by Taenia solium cysts in brain tissue?
|
convulsions
increased intracranial pressure neurologic disturbances |
|
|
where are adult tapeworms found when infected by Taenia solium by food or water contaminated with human feces?
|
adult tapeworms are not produced in this mode of infection
|
|
|
how do Taenia solium cysts evade host immune defenses?
|
produces taeniaestatin and paramyosin (inhibit complement activation)
|
|
|
what is the pork tapeworm?
|
Taenia solium
acquired by eating undercooked pork |
|
|
what is the beef tapeworm?
|
Taenia saginata
acquired by eating undercooked beef |
|
|
what is the fish tapeworm?
|
Diphyllobothrium latum
acquired by eating undercooked fish |
|
|
where does Taenia saginata live in humans?
|
only in gut
does not cause cysticerci |
|
|
where does Diphyllobothrium latum live in humans?
|
only in gut
doesn't form cysticerci |
|
|
what is Hydatid disease?
|
caused by ingestion of eggs of echinococcal species (esp. echinococcus granulosus)
presents as liver cysts, lung cysts, or bone cysts, or brain cysts |
|
|
what is the definitive host for Echinococcus granulosus? what is the usual intermediate host?
|
definitive - dogs
intermediate - sheep (humans accidentally) |
|
|
what are the definitive and intermediate hosts for Echinococcus multilocularis?
|
definitive - foxes
intermediate - rodents (humans accidentally) |
|
|
how are humans infected with Echinococcus spp.?
|
ingestion of food contaminated with eggs shed by dogs or foxes
eggs hatch in duodenum and invade the liver, lungs, or bones |
|
|
what are the common locations for cysticerci?
|
brain
muscles skin heart |
|
|
describe the cysts of cysticerci
|
ovoid, white to opalescent, often grape-sized, and contain an invaginated scolex with hooklets that are bathed in clear cyst fluid
may be intraparenchymal, attached to the arachnoid, or freely floating in the ventricular system |
|
|
what is hydatid sand?
|
fine, sandlike sediment within hydatid fluid caused by degenerating scolices of Echinococcus spp.
|
|
|
what type of organism is Trichinella spiralis?
|
nematode parasite acquired by ingestion of larvae in undercooked meat from infected animals (pigs, boars, or horses) infected by eating infected rats or meat products
|
|
|
what organism causes trichinosis?
|
Trichinella spiralis
nematode parasite |
|
|
what has decreased the number of Trichinella spiralis infected pigs?
|
laws requiring cooking of food or garbage fed to hogs
indirectly decreased number of human infections |
|
|
what happens to Trichinella spiralis larvae in the human gut?
|
develop into adults that mate and release new larvae, which penetrate into tissues
larvae disseminate hematogenously and penetrate muscle cells |
|
|
what are the signs/symptoms of trichinosis?
|
fever
myalgias marked eosinophilia periorbital edema less common: - dyspnea - encephalitis - cardiac failure |
|
|
what are the effects of Trichinella spiralis on striated muscle cells?
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T. spiralis becomes intracellular parasite in striated skeletal muscle
skeletal muscle loses striations, gains a collagenous capsule, and develops a plexus of new blood vessels around itself |
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what is a nurse cell?
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modified host skeletal muscle cell infected with and changed by Trichinella spiralis
modifications: - loses striations - gains a collagenous capsule - develops a plexus of new blood vessels around itself |
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what antibodies are useful in reducing recurrence of Trichinella spiralis?
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antibodies to larval antigens, including tyvelose (immunodominant carbohydrate epitope)
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what T cell reaction is triggered by nematodes?
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TH2 response
IL-4, IL-5, IL-10, IL-13 inc. intestinal contractility which expels adult worms from gut dec. number of larvae in muscle |
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where does Trichinella spiralis preferentially encyst?
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striated skeletal muscles with the richest blood supply, including diaphragm, extraocular, laryngeal, deltoid, gastrocnemius, and intercostal muscles
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what causes most of the mortality in schistosomiasis?
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hepatic cirrhosis, caused by Schistosoma mansoni in Latin America, Africa, and the Middle East as well as Schistosoma japonicum and Schistosoma mekongi in East Asia
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what is caused by Schistosoma haematobium?
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hematuria and granulomatous disease of the bladder, resulting in chronic obstructive uropathy
found in Africa |
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how is schistosomiasis transmitted?
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freshwater snails that live in slow-moving water of tropical rivers, lakes, and irrigation ditches
cercariae swim through fresh water and penetrate human skin with powerful proteolytic enzymes that degrade the keratinized layer |
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what are cercariae?
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infectious schistosome larvae
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what is the life cycle of Schistosomes?
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freshwater snail -> water -> penetrate human skin -> migrate to peripheral vasculature -> mature/mate in hepatic vessels -> migrate (male/female pairs) to pelvic veins -> females produce 100s of eggs/day -> eggs produce proteases for their passive transfer across intestine/bladder wall -> excretion of eggs in stool or urine -> infection of freshwater snails
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how do Schistosome eggs penetrate the wall of the intestine or bladder? why?
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produce proteases
must be excreted in either the urine or feces to infect freshwater snails and complete life cycle |
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what causes the severe pathology of Schistosomiasis?
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prominent inflammatory reaction to Schistosoma mansoni and Schistosoma japonicum eggs that are carried by portal circulation into the hepatic parenchyma
causes granulomas and hepatic fibrosis |
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how does acute schistosomiasis present?
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severe febrile illness that peaks about 2 months after infection
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what is the immune response during acute schistosomiasis?
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dominated by TH1 cells that produce IFN-gamma, which stimulates macrophages to secrete high levels of TNF, IL-1, and IL-6 (pyrogens)
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what is the immune response during chronic schistosomiasis?
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dominated by TH2 response, though TH1 cells persist
caused by parasite proteins that cause mast cells to produce IL-4, which induces TH2 differentiation and amplifies response |
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what is the serious manifestation of chronic schistosomiasis?
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severe hepatic fibrosis
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what cytokine, produced by TH2 cells, increases fibrosis?
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IL-13
seen to worsen the hepatic fibrosis in chronic schistosomiasis |
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what is seen in mild Schistosoma mansoni infections?
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white, pinhead-sized granulomas scattered throughout gut and liver
center of granuloma contains schistosome egg, which contains a miracidium surrounded by macrophages, lymphocytes, neutrophils, and eosinophils liver is darkened by regurgitate heme-derived pigments from the schistosome gut that are iron-free and accumulate in Kupffer cells and splenic macrophages |
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what is seen in mild Schistosoma japonicum infections?
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white, pinhead-sized granulomas scattered throughout gut and liver
center of granuloma contains schistosome egg, which contains a miracidium surrounded by macrophages, lymphocytes, neutrophils, and eosinophils liver is darkened by regurgitate heme-derived pigments from the schistosome gut that are iron-free and accumulate in Kupffer cells and splenic macrophages |
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what is seen in severe Schistosoma mansoni infections?
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inflammatory patches (pseudopolyps) in the colon
surface of liver is bumpy and cut surfaces reveal granulomas and widespread fibrosis as well as portal enlargement without intervening regenerative nodules fibrosis often obliterates the portal veins (portal hypertension, splenomegaly, esophageal varices, and ascites result) granulomatous pulmonary arteritis with intimal hyperplasia, progressive arterial obstruction and ultimately cor pulmonale |
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what is pipe-stem fibrosis?
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fibrous triad of granulomas, sidespread fibrosis and portal enlargement without regenerative nodules, produced by Schistosoma mansoni and Schistosoma japonicum infections
resembles the stem of a clay pipe |
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what is seen in severe Schistosoma japonicum infections?
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inflammatory patches (pseudopolyps) in the colon
surface of liver is bumpy and cut surfaces reveal granulomas and widespread fibrosis as well as portal enlargement without intervening regenerative nodules fibrosis often obliterates the portal veins (portal hypertension, splenomegaly, esophageal varices, and ascites result) granulomatous pulmonary arteritis with intimal hyperplasia, progressive arterial obstruction and ultimately cor pulmonale |
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for what condition are people with hepatosplenic schistosomiasis at increased risk?
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mesangioproliferative or membranous glomerulopathy
(glomeruli contain deposits of immunoglobulin and complement but rarely schistosome antigen) |
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what is seen in Schistosoma haematobium infection?
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inflammatory cystitis caused by massive egg deposition
granulomas appear early and cause mucosal erosions as well as hematuria later, granulomas calcify and develop a sandy appearance (if severe, this may line the wall of the bladder and cause a dense concentric rim/calcified bladder seen on x-ray |
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what is the most frequent complication of infections with Schistosoma haematobium?
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inflammation and fibrosis of the ureteral walls, leading to obstruction, hydronephrosis, and chronic pyelonephritis
there is also association between urinary schistosomiasis and squamous cell carcinoma of the bladder |
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how is lymphatic filariasis transmitted?
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mosquitoes
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how is Wucheria bancrofti transmitted?
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mosquito bites
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how is Brugia malayi transmitted?
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bites from infected mosquitoes
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how is Brugia timori transmitted?
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bites from infected mosquitoes
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what organisms cause Lymphatic filariasis?
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Wuchereria bancrofti (90%)
Brugia malayi + Brugia timori (10%) closely related infectious nematodes transmitted by mosquitoes |
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what disease is caused by Wuchereria bancrofti?
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lymphatic filariasis
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what disease is caused by Brugia spp. of nematodes?
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lymphatic filariasis
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in what areas is lymphatic filariasis endemic?
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Latin America
sub-Saharan Africa Southeast Asia |
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what types of disease are caused by filariasis?
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1) asymptomatic microfilaremia
2) recurrent lymphadenitis 3) chronic lymphadenitis with swelling of the dependent limb or scrotum (elephantiasis) 4) tropical pulmonary eosinophilia |
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what is elephantiasis?
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chronic lymphadenitis with swelling of the dependent limb or scrotum caused by filariasis infection (Wuchereria bancrofti, Brugia malayi, or Brugia timori)
chronically swollen limb develops tough subcutaneous fibrosis and epithelial hyperkeratosis |
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where do infective larvae of Wuchereria bancrofti develop into adult male and female worms?
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lymphatic channels
worms mate and release microfilariae into the bloodstream (applies to Brugia malayi and Brugia timori also) |
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what is taken up by mosquitoes who bite humans infected with Wuchereria bancrofti?
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microfilariae
can then transmit filariasis (applies to Brugia malayi and Brugia timori also) |
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what are the filarial molecules that enable Wuchereria bancrofti, Brugia malayi and Brugia timori to evade or inhibit immune defenses?
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- surface glycoproteins with antioxidant function
- homologues of cystatins (impair MHC class II antigen processing pathway) - serpins (inhibit neutrophil proteases) - TGF-beta homologues (downregulates immune responses) |
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what are cystatins?
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cysteine protease inhibitors, which can impair MHC class II antigen-processing pathway
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what are serpins?
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serine protease inhibitors, which can inhibit neutrophil proteases
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what bacteria has an endosymbiotic relationship with filarial nematodes?
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Wolbachia (ricketsia-like bacteria)
it is necessary for nematode development and reproduction |
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with what parasite does Wolbachia have an endosymbiotic relationship?
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Wolbachia is a rickettsia-like bacteria that has an endosymbiotic relationship with filarial nematodes (Wuchereria bancrofti, Brugia malayi, Brugia timori)
it is necessary for nematode development and reproduction |
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how do antibiotics help to treat lymphatic filariasis?
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kill Wolbachia, an endosymbiotic rickettsia-like bacteria that infects filarial nematodes and is necessary for the development and reproduction of the filarial nematodes
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what causes damage to the lymphatic system in chronic lymphatic filariasis?
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direct damage by adult parasites
damage by TH1-mediated immune response |
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are microfilariae commonly found in the bloodstream?
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no - most often they are absent
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what is tropical pulmonary eosinophilia?
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IgE-mediated hypersensitivity (type I HSN reaction) to microfilariae (Wuchereria bancrofti, Brugia malayi, Brugia timori)
seen most commonly in individuals of Souther Asian descent or in norther Latin America Ige stimulated by IL-4, eosinophils stimulated by IL-5, both are produced by filaria-specific TH2 cells |
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what are the characteristics of chronic filariasis?
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persistent lymphedema of the extremities, scrotum, penis, or vulva
frequently there is hydrocele and lymph node enlargement in severe/long-lasting infections, chylous weeping of enlarged scrotum or chronically swollen leg may develop tough subcutaneous fibrosis and epithelial hyperkeratosis (elephantiasis) |
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what is present in the draining lymphatics or nodes of a filarial nematode-infected leg?
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adult filarial worms, whether alive, dead, or calcified, surrounded by:
- mild or no inflammation - intense eosinophili with hemorrhage and fibrin - granulomas |
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what is a hydrocele?
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fluid-filled sack along the spermatic cord within the scrotum
Sx: painless, swollen testicle, which feels like a water balloon; may occur on one or both sides |
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what are Meyers-Kouvenaar bodies?
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dead microfilariae (Wuchereria bancrofti, Brugia malayi, Brugia timori) surrounded by stellate, hyaline, eosinophilic precipitates embedded in small epitheloid granulomas found in the lungs of some patients without other manifestations of filarial disease
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what organism causes Onchocerciasis?
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Onchocerca volvulus
filarial nematode transmitted by black flies |
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what type of organism is Onchocerca volvulus?
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filarial nematode transmitted by black flies
causes Onchocerciasis |
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what has dramatically reduced the incidence of Onchocerca volvulus infection in West Africa?
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aggressive campaign of ivermectin
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what is the second most common preventable cause of blindness in sub-Saharan Africa?
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Onchocerca volvulus infection
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what is river blindness?
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blindness caused by Onchocerca volvulus
prevalent near some rivers second most common cause of preventable blindness in sub-Saharan Africa |
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where do adult Onchocerca volvulus nematodes mate?
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in the dermis
surrounded by mixed infiltrate of host cells that produces an onchocercoma (characteristic subcutaneous nodule) |
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what is an onchocercoma?
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characteristic subcutaneous nodule caused by Onchocercoma volvulus mating in the dermis, surrounded by a mixed infiltrate of host cells
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what causes the main pathologic process (blindness) in Onchocerciasis?
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large numbers of microfilariae (Onchocerca volvulus), released by females, that accumulate in the skin and eye chambers
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what causes punctate keratitis in Onchocerciasis?
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inflammation around a degenerating microfilaria
sometimes accentuated by treatment with antifilarial drugs (Mazzotti reaction) |
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why does Onchocerca volvulus repopulate the host a few months after treatment with Ivermectin?
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Ivermectin kills only immature worms; the adult worms live on and repopulate
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what bacteria has an endosymbiotic relationship with Onchocerca volvulus?
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Wolbachia (endosymbiotic with all filarial nematodes, including Wuchereria bancrofti, Brugia malayi, and Brugia timori)
necessary for reproduction and survival |
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why is doxycycline an effective treatment for Onchocerciasis?
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Onchocerca volvulus is a filarial nematode and therefore must be infected with Wolbachia (a symbiotic Rickettsia-like bacteria) in order to survive and reproduce
doxycycline kills Wolbachia and blocks reproduction of O. volvulus for up to 24 months |
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how does Onchocerca volvulus infection present?
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itchy dermatitis with focal darkening or loss of pigment and scaling (leopard, lizard, or elephant skin)
foci of epidermal atrophy and elastic fiber breakdown may alternate with areas of hyperkeratosis, hyperpigmentation with pigment incontinence, dermal atrophy, and fibrosis |
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what is an onchocercoma composed of?
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fibrous capsule surrounding adult worms and a mixed chronic inflammatory infiltrate that includes fibrin, neutrophils, eosinophils, lymphocytes, and giant cells
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what are the progressive eye lesions caused by Onchocerca volvulus?
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begin with punctate keratitis along with small, fluffy opacities of the cornea caused by degenerating microfilariae evoking an eosinophilic infiltrate
followed by sclerosing keratitis that opacifies the cornea, beginning at the scleral limbus microfilariae in anterior chamber cause iridocyclitis and glaucoma microfilariae in choroid and retina cause atrophy and loss of vision |
