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1500 Cards in this Set

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what are prions composed of?
abnormal forms of a host protein called prion protein (PrP)
with what is kuru associated?
human cannibalism
what are the prion diseases?
kuru
creutzfeldt-jakob disease (CJD)
bovine spongiform encephalopathy (BSE/mad cow disease)
variant creutzfeldt-jakob disease
how is variant creutzfeldt-jakob disease transmitted to humans?
from BSE-infected cattle
what is PrP?
prion protein

abnormal form of host protein that composes prions

normally found in neurons
where is PrP usually found?
neurons
what change occurs in PrP, causing prion diseases?
conformational change that renders it resistant to proteases

protease-resistant PrP promotes the conversion of normal protease-sensitive PrP to the abnormal form
how can creutzfeldt-jakob disease be transmitted from person to person?
iatrogenically
by surgery
organ transplant
blood transfusion
define iatrogenic
an inadvertent adverse effect or complication resulting from medical treatment or advice, including that of psychologists, therapists, pharmacists, nurses, and dentists
viruses
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)
what inclusions are produced by cytomegalovirus?
large eosinophilic nuclear inclusion

smaller basophilic cytoplasmic inclusions
what inclusions are produced by herpesviruses?
large nuclear inclusion surrounded by a clear halo
what is a latent infection?
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)
describe the latent infection with herpes zoster virus
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)
bacteria
prokaryotes

have a cell membrane, but no membrane-bound organelles; surrounded by a wall of peptidoglycan

can be extracellular, facultative intracellular, or obligate intracellular
how do prokaryotes differ from eukaryotes?
both have cell membranes

eukaryotes have membrane-bound organelles, but prokaryotes do not
pili
surface projections in bacteria that can adhere to host cells or extracellular matrix
what is the difference in peptidoglycan between gram-positive and gram-negative bacteria?
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
where are both staphylococcus epidermidis and propionibacterium acnes typically found to colonize?
skin
what bacteria causes acne?
propionibacterium acnes
what is the major contributor to dental plaque?
aerobic and anaerobic bacteria in the mouth, particularly streptococcus mutans
define microbiome
the totality of microbes, their genetic elements (genomes), and environmental interactions in a defined environment
give examples of obligate intracellular bacteria
chlamydia (epithelial cells)
rickettsia (endothelial cells)

replicate in membrane-bound vacuoles in specific cells identified

get most/all of their energy from host cell
what is the most frequent infectious cause of female sterility?
chlamydia trachomatis

causes scarring and narrowing of the fallopian tubes
what is the most frequent infectious cause of blindness?
chlamydia trachomatis

causes chronic inflammation of the conjunctiva that eventually causes scarring and opacification of the cornea
what generic diseases are caused by rickettsiae?
injure endothelial cells, causing a hemorrhagic vasculitis, often visible as a rash

injure CNS & cause death (rocky mountain spotted fever; epidemic typhus)
how are rickettsiae transmitted?
arthropod vectors

lice (epidemic typhus)
ticks (rocky mountain spotted fever; ehrlichiosis)
mites (scrub typhus)
how are mycoplasma and ureaplasma unique among extracellular bacterial pathogens?
do not have a cell wall

tiniest free-living organisms known (125-300nm)
fungi
eukaryotes

thick chitin-containing cell walls; ergosterol-containing cell membranes
what is thermal dimorphism?
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
what are the two types of spores produced by fungi?
sexual spores

asexual spores (aka conidia)
what are conidia?
asexual spores of fungi

produced on specialized fruiting bodies arising along the hyphal filament
what are dermatophytes?
fungal species whose infections are confined to the superficial layers of the skin
where is coccidioides geographically restricted to?
southwestern united states
where is histoplasma geographically restricted to?
ohio river valley
what is the effect of opportunistic fungi on immunocompromised individuals?
give rise to life-threatening infections

characterized by tissue necrosis, hemorrhage, and vascular occlusion, with little/no inflammatory response
what fungus commonly infects AIDS patients?
pneumocystis jiroveci (formerly called pneumocystis carinii)
protozoa
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
in what type of cells does Leishmania replicate?
macrophages
what are the most prevalent intestinal protozoans?
entamoeba histolytica

giardia lamblia
what are the two forms of entamoeba histolytica?
motile trophozoites (attach to intestinal epithelial wall and may invade)

immobile cysts (resistant to stomach acids and infectious when ingested)
what are the two forms of giardia lamblia?
motile trophozoites (attach to intestinal epithelial wall and may invade)

immobile cysts (resistant to stomach acids and infectious when ingested)
how are blood-borne protozoans transmitted? give some examples
insect vectors where they replicate before being passed to new human hosts

plasmodium, trypanosoma, leishmania
how is toxoplasma gondii acquired?
contact with oocyst-shedding kittens

eating cyst-ridden, undercooked meat
helminths
highly differentiated multicellular organisms

most alternate btwn sexual reproduction in definitive host and asexual multiplication in intermediate host or vector
what happens once adult helminths take up residence in humans?
do not multiply

produce eggs or larvae that are passed out in stool
to what is the severity of helminth-mediated disease proportional?
number of organisms that have infected the individual
what are ectoparasites?
insects (lice, bedbugs, fleas) or arachnids (mites, ticks, spiders) that attach to and live on or in the skin
how do arthropods produce disease?
directly (damaging human host)

indirectly (serving as vectors for transmission of infectious agents)
what causes pediculosis?
lice attached to hair shafts
what is pediculosis?
infestation with lice
what is scabies?
infestation of skin with mites

mites burrow into the stratum corneum
what are the layers of epidermis from outside-in?
stratum corneum
stratum lucidum (only in thick skin)
stratum granulosum
stratum spinosum
stratum basale
what is the malphigian layer?
stratum spinosum and stratum basale as a unit (both considered together)
what can be found at the site of an arthropod bite?
mouth parts associated with a mixed infiltrate of lymphocytes, macrophages, and eosinophils
what is gram staining used for?
most bacteria
what is acid-fast stain used for?
mycobacteria
nocardia
what is silver stain useful for?
fungi
legionellae
pneumocystis
what is periodic acid-Schiff useful for?
fungi
amoebae
what is mucicarmine stain useful for?
cryptococci (encapsulated yeast)

stains the capsule
what is giemsa stain useful for?
campylobacter
leishmaniae
malaria
what are antibody probes useful for identifying?
all classes of microorganisms
what are cultures useful for identifying?
all classes of microorganisms
what are DNA probes useful for identifying?
all classes of microorganisms
where are organisms usually best visualized?
advancing edge of a lesion, particularly if there's necrosis

(not at the center)
what is indicated by the presence of microbe-specific IgM antibodies in the serum shortly after the onset of symptoms?
diagnostic of infection by the specific microbe
how can an infection be diagnosed with antibody titers?
specific antibody titers can be measured early (acute) and 4-6 weeks (convalescent) after infection

four-fold rise in titer is usually considered diagnostic
what are molecular diagnostics?
nucleic acid-based tests for detecting and quantifying various pathogens
treatment of what types of infections is guided by nucleic acid-based measurements?
management of HBV and HCV infections is guided by nucleic acid-based viral quantification/typing

predicts resistance to antiviral drugs
compare PCR testing for herpes simplex virus with cultures in herpes simplex virus encephalitis
PCR testing has a sensitivity of 80%

culture has a sensitivity of less than 10%
what is the manifestation of the ebola virus?
epidemic ebola hemorrhagic fever
what is the manifestation of the hantaan virus?
hemorrhagic fever with renal syndrome
what is the manifestation of legionella pneumophila?
legionnaires disease
what is the manifestation of campylobacter jejuni?
enteritis
what is the manifestation of human t-lymphocyte virus?
aka HTLV-1

T-cell lymphoma or leukemia
HTLV-associated myelopathy
what is the manifestation of Staphylococcus aureus?
toxic shock syndrome
what are the manifestations of escherichia coli O157:H7?
hemorrhagic colitis
hemolytic-uremic syndrome
what is the manifestation of borrelia burgdorferi?
lyme disease
what is the manifestation of HIV?
aka human immunodeficiency virus

acquired immunodeficiency syndrome (AIDS)
what is the manifestation of helicobacter pylori?
gastric ulcers
what is the manifestation of hepatitis E?
enterically transmitted hepatitis
what is the manifestation of hepatitis C?
hepatitis C
what is the manifestation of vibrio cholerae O139?
new epidemic cholera strain
what is the manifestation of bartonella henselae?
cat-scratch disease
what is the manifestation of HHV-8?
HHV8 = kaposi sarcoma herpes virus

kaposi sarcoma in AIDS
what is the manifestation of west nile virus?
west nile fever
neuroinvasive disease
what is the manifestation of the SARS coronavirus?
severe acute respiratory syndrome
what are the CDC categories for ranking bioweapons?
A - highest risk/most dangerous

B- intermediately dangerous

C - could be engineered to be dangerous
describe category A bioterrorism agents
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
why is smallpox a category A bioweapon?
easily transmissable in any climate/season

30% mortality rate

lack of effective antiviral therapy
why is smallpox easily disseminated?
it is very stable in aerosol form

a very small dose is needed for infection
how is smallpox naturally spread?
direct contact with virus in skin lesions or contaminated clothing or bedding
what are the symptoms of smallpox infection?
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
when do symptoms of smallpox infection appear?
7-17 days after infection
why is the population susceptible to smallpox infection if there is a vaccine?
vaccination ended in the US in 1972

vaccination immunity has waned
what type of bioweapon is anthrax?
bacillus anthracis

category A
what type of bioweapon is botulism?
clostridium botulinum toxin

category A
what type of bioweapon is yersinia pestis?
aka the plague

category A
what type of bioweapon is smallpox?
variola major virus

category A
what type of bioweapon is francisella tularensis?
causes tularemia

category A
what type of bioweapon are filoviruses?
e.g. ebola and marburg viruses

cause viral hemorrhagic fevers

category A
what type of bioweapon are arenaviruses?
e.g. Lassa and machupo viruses

cause viral hemorrhagic fevers

category A
what type of bioweapon is Brucella sp.?
causes brucellosis

category B
what type of bioweapon is the epsilon toxin of clostridium perfringens?
category B
what type of bioweapon are food safety threats?
e.g. salmonella sp., E. coli O157:H7, shigella

category B
what type of bioweapon is burkholderia pseudomallei?
causes melioidosis

category B
what type of bioweapon is burkholderia mallei?
causes glanders

category B
what type of bioweapon is chlamydia psittaci?
causes psittacosis

category B
what type of bioweapon is coxiella burnetti?
causes Q fever

category B
what type of bioweapon is ricin toxin?
from ricinus communis (castor beans)

category B
what type of bioweapon is staphylococcal enterotoxin B?
category B
what type of bioweapon is rickettsia prowazekii?
causes typhus fever

category B
what type of bioweapon are alphaviruses?
e.g. venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis

cause viral encephalitis

category B
what type of bioweapon are water safety threats?
e.g. vibrio cholerae, cryptosporidium parvum

category B
what type of bioweapon is Nipah virus?
category C
what type of bioweapon is Hantavirus?
category C
describe category B bioweapons
moderately easy to disseminate

produce moderate morbidity, but low mortality

require specific diagnostic and disease surveillance

many are food- or water-borne
describe category C bioweapons
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
what are the first defenses against infection?
intact skin and mucosal surfaces

physical barriers that produce antimicrobial substances
what factors about the skin make it a good first line of defense?
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
what potential opportunists are normal flora of the skin?
staphylococcus epidermidis
candida albicans
what is infected by dermatophytes?
stratum corneum
hair
nails
how do Schistosoma larvae, released from freshwater snails enter the body?
penetrate swimmers' skin by releasing collagenase, elastase, and other enzymes that dissolve the extracellular matrix
what fungus is commonly found in burns?
pseudomonas aeruginosa
how are most GI pathogens transmitted?
food or drink contaminated with fecal material
what are the normal defenses of the GI tract?
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
what are defensins?
mucosal antimicrobial peptides
where are secreted IgA antibodies made?
plasma cells located in mucosa-associated lymphoid tissues (MALT)
what are M cells?
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
what type of viruses are inactivated by bile and digestive enzymes?
enveloped viruses

nonenveloped viruses may be resistant to bile and digestive enzymes
how do staphylococcal strains cause GI disease?
while growing on contaminated food, they release powerful enterotoxins that cause food poisoning without any bacterial multiplication in the gut
how do V. cholerae and E. coli cause GI disease?
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
how do shigella, salmonella, and campylobacter cause GI disease?
invade and damage intestinal mucosa and lamina propria

cause ulceration, inflammation, and hemorrhage

clinically manifested as dysentery
how does salmonella typhi cause GI disease?
passes from damaged mucosa, through Peyer patches and mesenteric lymph nodes, and into the blood stream

results in systemic infection
when does fungal infection of the GI tract occur?
mainly in immunologically compromised people
in what form must intestinal protozoans be to infect?
cyst form, because cysts resist stomach acid

convert to motile trophozoites in the gut
how do protozoans infect the intestines?
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
what happens to Giardia lamblia when it attaches to sugars on intestinal epithelia?
attaches to epithelial brush border and multiplies there
what happens to cryptosporidia after it attaches to sugars on intestinal epithelia?
taken up by enterocytes, in which they form gametes and spores
what happens to Entamoeba histolytica after it attaches to sugars on intestinal epithelia?
causes contact-mediated cytolysis through a channel-forming pore protein

ulcerates and invades colonic mucosa
when do intestinal helminths cause disease?
present in large numbers

present in ectopic sites
how does Ascaris lumbricoides cause disease?
obstructs the gut

invades and damages bile ducts
how do hookworms cause disease?
cause iron deficiency anemia by chronic loss of blood sucked from intestinal villi
how does Diphyllobothrium latum cause disease?
depletes host of vitamin B12, giving rise to illness resembling pernicious anemia
what is the fish tapeworm?
Diphyllobothrium latum
where do larvae of Trichinella spiralis preferentially encyst?
muscle
where do echinococcus species larvae preferentially encyst?
liver
lung
on what is the distance particles travel into the respiratory system dependent?
inversely proportional to size
where are large particles trapped in the respiratory tract?
mucociliary blanket that lines nose and upper respiratory tract
what is the host defense mechanism to particles/microbes that are inhaled?
trapped in mucus secreted by goblet cells

transported by ciliary action to the back of the throat

swallowed and cleared
what happens to particles smaller than 5um?
travel directly to alveoli

phagocytosed by alveolar macrophages or by neutrophils recruited to the lungs by cytokines
what is necessary for microorganisms that invade normal healthy respiratory tract?
must have developed specific mechanisms to overcome the mucociliary defenses or to avoid destruction by alveolar macrophages
what mechanisms have influenza viruses developed to infect respiratory tract defenses?
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
what mechanisms have influenza viruses developed to exit respiratory tract epithelial cells?
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
why is neuraminidase a good target for anti-influenza drugs?
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
what bacteria elaborate toxins that paralyze respiratory mucosal cilia?
Haemophilus influenzae
Bordetella pertussis
what is the major cause of severe respiratory infection in persons with cystic fibrosis?
Pseudomonas aeruginosa
what bacteria produces ciliostatic substances?
M. pneumoniae
how do streptococcus pneumoniae and staphylococcus species infect the respiratory tract, even though they don't have specific adherence factors?
gain access after viral infection causes a loss of ciliated epithelium

individuals with viral respiratory infection are more susceptible to secondary bacterial superinfections
how is the urogenital tract mostly infected?
most urinary tract infections invade from the exterior via the urethra
what is the normal defense against invading microorganisms in the urinary tract?
regular flushing with urine
what microorganisms are usually found in urine of a healthy individual?
a healthy person's urine is usually sterile in the bladder
how do successful urinary tract pathogens infect?
e.g. N. gonorrhoeae, E. coli

adhere to urinary epithelium
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
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
what is the presentation of pyelonephritis?
fever, accelerated heart rate, painful urination, abdominal pain radiating to the back, nausea, and tenderness at the costovertebral angle on the affected side
what is the normal defense mechanism of the vagina against microorganisms?
low pH resulting from catabolism of glycogen in the normal epithelium by lactobacilli
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
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
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
what viruses are transported free in plasma?
poliovirus
hepatitis B virus
what protozoa are transported free in the plasma?
African trypanosomes
what helminths are transported free in the plasma?
all
what organisms are transported by leukocytes in the blood?
herpesviruses
HIV
mycobacteria
Leishmania (protozoan)
Toxoplasma (protozoan)
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)
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
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
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
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
what are the major manifestations of schistosoma hematobium?
cystitis

penetrates through the skin, but localizes in the urinary bladder
what are the possible consequences of bacterial or mycoplamal placentitis?
premature delivery

stillbirth
what are the possible consequences of viral infections of a fetus?
maldevelopment of the fetus

infection in early pregnancy results in most severe disease
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
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
what is the major cause of AIDS in children?
maternal transmission of HIV
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
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