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163 Cards in this Set

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T/F innate host defeneses are very important for defense against fungal infections
True. Barriers such as the skin, mucous membranes, phagocytes, and neutronphils are very important in preventing fungal infections.
Which type of adaptive immunity is most important for presenting fungal infections, humoral of cell mediated?
Final clearnace of invading fungi requires effecive specific CMI using antigen specific CD4's and activated macrophages. Humoral immunity is not very helpful
T/F the humoral immune response does not participate in fighting off fungal infections
False. Even though CMI is more important, the humoral resposne still participates. Fungi can elicit antibodies, bind complement, and become opsonized and phagocytosed. Even though this happens, natural antibody responses are not protective.
Describe three ways that a compromise of a skin barrier may increase host suceptibility to a fungal infection
1. Burns- airbore fungi can settle on burns or severe wounds e.g. Aspergillis species
2. Traumatic implantation cause introduce soil fungi e.g. zygomycetes, sporothrix
3. Nosocomial infection from commensal skin fungi e.g. Candida alibicans
How might a reduction or alteration of a host's normal micribial flora make them more suceptible to fungal infection
The normal flora protects the host by serving as a barrier and modulating the microenvironmental niche. Factors that change the biota like anitibiotics, hormonal varation, steriods, etc can change this composition and give pathogens a chance to take hold. e.g. female on antibiotics more suceptible to yeast infections
How might inherited cellular immunodeficiencies make a host more suceptible to fungal infections
Inherited defects in the presence or function of phagocytes (neuts, macs) or T cells increase suceptibility to fungal infections. Examples are Chronic granulomatous disease which is a defect in the oxidative killing mechanism of phagocytes and Severe Combined Immunodeficiency which is characterized by a lack of mature B and T cells.
How might cancer increase host suceptibility to fugal infections
Reduction in number and function of immune cells, of particular concern are lymphohematologic malignancies.
How might hospitalization increase host suceptibility to fungal infection
-immunocompromised patients
-antibiotic use
-invasive procedures
Why are those at the extremes of age particularly vulnerable to fungal infections
Young-immaturity of the adaptive immune response
Old- declining capacity of adative immune response
List some examples of how other infections may increase host suceptibility of fungal sequele
-Immunomodulating viurses like herpesvirues, CMV, EBV
-HIV infection
List 8 situations that can decrease host defense and make them more suceptible to fungal infections
1. compromise of skin barrier
2. alteration of normal flora
3. inherited immunodeficiency
4. cancer
5. Immunsupressive therapy
7. Extremes of age
8. Other infections
Describe thermotolerance as a fungal virulence factor
THe ability to grow at 37C is a rare trait among fungi but is required for mamalian infection.
Describe adhesion as a fungal virulence factor
Fungi must have a mechanism to bind to host cells or extracellular matrix
List for general ways for fungi to evade the host immune response
1. Larger size makes phagocytosis difficult
2. Resistance to complement mediated lysis (polysacchride cell wall prevents attack by MAC)
3. biofilm formation
4. polysaccharide capusles
List two general ways in which fungi obtain iron from the host
1. Siderophores compete with host iron binding compounds and scavenge for free iron
2. Reduction of Fe3+ to Fe2+ which releass iron from host transferrin
Give some general examples of host damaging compounds produced by fungi
-hydrolytic enzymes
List 4 systemic fungal pathogens and the diseases associated with them
Histoplasma capsulatum- histoplasmosis
Blastomyces dermatitidis- blastomycosis
Coccidioides immitis and posadasii- coccidioidomycosis (valley fever)
Paracoccidioides brasiliensis-paracoccidioidomycosis
describe the dimorphism associated with systemic fungal pathogens
Morphology is generally thermally regulated. Each organism assumes one form in the environment and another in the host. All are molds in the environment. Hc, Bd, and Pb are yeasts in the host, Coccidioides spp. are endosporulating spherules in the host
How does infection with a thermal dimorph occur
Infection occurs via the respiratory route by inhalation of infectious mold particles that are small enough to get into the small airways. After entry, the pathogen converts to the host form (yeast or E.S.). Direct inoculation is also possible but is rare (usually laboratory workers)
Are thermal dimorphic fungi contagious (spread person to person)?
No, they are not normally spread person to person. Mold elements are inhaled from the environment
What is a common sign of a disseminated infection amongst all four of the thermal dimorphs
dermatological manifestations
Describe the mold form of Histoplasma capsulatum
-multinucleate branched hyphae (mycelia) with tuberculate macroconidia and microconidia
-mold form found in soil and room temp
-perfers moist soil and temperate climates
-associated with bird or bat guano
The saprobic (free living) form of Histoplasma capsulatum is (noninfectious/infectous) and (nonpathogenic/ pathogenic)
The saprobic form of Hc is infectious but nonpathogenic. The conidia of the mold form are inhaled but Hc must convert to a yeast in the host for pathogenesis to occur
Describe the yeast form of Histoplasma capsulatum
-parasitic form found in host or in lab at 37C
-uninucleate oval budding yeast with narrow bud neck (contrast to Blasto)
-found in the host extracellularly and inside antimicrobial cells like macrophages (facultative intracellular pathogen)
The parasitic (yeast) form of Histoplasma capsulatum is (noninfectious/infectous) and (nonpathogenic/ pathogenic)
The yeast form of Hc is noninfectious but pathogenic. The conidia of the mold form are inhaled but Hc must convert to a yeast in the host for pathogenesis to occur
What family of fungi does Histoplasma capsulatum belong to? List some other fungi that belong to this family.
Ascomycete. Includes S. cerevisiae, Candida spp., Aspergillus spp.
Hc is very closely related to Blastomyces dermatiditis
Describe the sex/mating by mold morphotype of Histoplasma capsulatum
-teleomorphic or perfect state know as Ajellomyces capsulatum
-Heterothallic (2 mating types)
-No mating or genetic exchange by yeast (only mold)
What are the three variants of Hc and where are they found
Hc var capsulatum
Hc var duboisii- African Histoplasmosis
Hc var farciminosum- equine histoplasmosis
Where is Hc classically found
Mississippi and Ohio river valleys- American Midwest and South
Also common in American Southwest, Latin America, and Africa
describe the ideal soil conditions for Hc
-moist, rich with high nitrogen content, temperate climate
-particularly associated with guano from birds or bats (birds are not infected but rather their poop provides a favorable growth environment, bats as mammals can be infected and shed the fungus in their poo)
What is the major route of Hc infection
Inhalation of conidia or mycelial fragments. Organism then rapidly (several hours) converts to yeast within the host and replicates within macrophages. The main infectious form is microconidia because their small size allows them easier access to the small airways
Describe Hc binding to macrophages
Binding via the CD18 (B2 integrin subunit) receptor family of mammalian surface glycoprotein receptors. These receptors are found on monocytes, macrophages, and neutrophils.
In addition to macrophages, neutrophis and monocytes, what other cells can Hc infect. How?
epithelial cells
dendritic cells via the fibronectin receptor
Describe the incidence of Hc infection
-most common fungal respiratory infection in the world
-Most common systemic mycosis in the US with 500,000 new infections annually
What are the three different epidemiologic ways clinically significant Hc can occur in immunocompetent people
1. Large epidemics caused by construction etc.
2.Small outbreaks linked to specific exposure (kids in cave, farm workers)
3. Sporadic individual cases
What aspects of Hc infection do defects in CMI increase
-increased risk of active primary disease on initial exposure
-increased risk of reactivation of latent infection
-increased risk of severe systemic disease
Describe the typical clinical presentation of Hc infection
for immunocompetent people: nonspecific respiratory flu like sxs that resolves <5% bring about medical attention, clinically significant or severe disease is rare
T/F if an immunocompetent person recovers from an Hc infection, the organism will no longer be in their body
False. Resolution of the primary infection does no indicate clearance of the organism. Long term, perhaps lifelong, latent infection occurs regardless of the presentation or severity of the initial infection.
What are the 5 possible locations of Hc infections
1. pulmonary (can lead to histoplasmoma or fungus ball in emphysema pts)
2. pericarditis (consequence of host immune response)
3. Disseminated (occurs via extracellular blood or lymph in intracellular in migratory macs)
4. mucocutaneous
5. ocular (consequence of host immune response)
mnemonic= Pretty Please Don't Mimic Ohio
What initial presentation is typical of African histoplasmosis (H. duboisii) and not of Hc var capsulatum
bone and skin involvement
Describe the initial immune reaction to Hc
the infection is contained with antigen specific CD4 T cell stimulated macrophages
Explain Hc latency in terms of the host immune response
Activated macrophages contain the infection in a fungistatic state but it is difficult (maybe impossible) to induce fungicidal activity. This allows Hc to establish a latent infection
How is Hc infection presumptively Dx'ed
Histopathology showing typical narrow bud yeast
How is Hc definitivley Dx'ed (3 ways)
1. culture with demonstrated temperature regulated dimorphism (very long)
2. Presence of Hc exoantigen in urine ( fast 1-2 days)
3. Reactivity with specific DNA probes
How might a Hx of prior Hc infection be demonstrated (3 ways)
1. Skin test (delayed type hypersensitivity against histoplasmin which includes H antigen and M antigen)
2. Serum antibody direction against H and M antigens via Western blot
3. radiographic calcifications (esp lung. spleen)
How can infection with Hc be prevented
-NO vaccine
-disinfection and respiratory barrier protection at high risk areas
-Oral antifungal prophylaxis in AIDS pts in endemic areas
How is Hc infection treated
-note that despite Tx, host may never erradicate Hc but active disease can be resolved
-immunocomp. may require lifelong antifungal
-IV Amphotericin B is effective but toxic
-Liposomal amphotericin B (expensive and requires approval)
-oral or IV Itraconazole for less severe disease, after resolution of acute disease in immnocomp, or for prophylaxis
What is the purpose of PCMS
drug that locks dimorphs in mycelial morphotype, used experimentally to demonstrate the need to transition to yeast to be infective
What is DRK1
Hc gene that is essential for dimorphism. It encodes a Dimorphism Regulating histidine Kinase.
Gene disruption or RNAi downregulation results in failure to convert from mold to yeast and loss of virulence in mouse model
List several features that create a hostile phagolysosomal environment that must be sensed and either abrogated or survived by Hc
oxidative burst, acid pH, proteases, hydrolytic enzymes, limitation of iron, defensis, nitric oxide
mnemonic= Pregnant Owls Need Always Prowl in Darkness
Entry into a host phagocyte by host directed phagocytosis of opsonized (antibody or complement) particles is usually associated with oxidative burst. How does Hc get around/ survive this event so that it can replicate in host macrophages? (2 ways)
1. bind//entry via a distinct pathway (bind macs by CD18 or DCs by fibronectin) this may help avoid burst and alters intracellular localization
2. Secrete catalase
What is the significance of Hc Heat Shock Protein 60 (HSP60)
-found both intracellullarly (weird for a eukaryotic HSP) and on cell surface
-mitochondrial chaperone
-adhesin for binding host cells
-immunogenic, stimulates CD4 t cells (protective antigen in mice)
-directly stimulates macrophages (could make adjuvant contribution)
How does Hc avoid/ survive host pH dependent antimicrobial defenses (2 ways)
1. survival of a vast range of pH (2-12 in vitro)
2. Modulation of macrophage phagolysosome pH either by inhibition or reversal of acidification (unknown mechanism but could be inhibition of membrane acidification mechanism, secretion of buffers)
List 5 potential mechanisms of Hc iron sequestration
1. pH dependent release of iron from transferrin (a normal cell process in the phagolysosome to get the cell iron but Hc could take advantage)
2. Secretion of siderophores (hydroxamate class)
3. Secretion/ surface expression of ferric iron reducing agents (reduced iron is released from Tf and siderophores)
4. Expression of surface molecules that bind host iron containing compounds like hemin
5. Proteolytic activity that degrades host iron binding proteins
mnemonic= Perhaps Sluts Really Prefer Boys (pH, Siderophore, Reduction, bind, proteolysis)
What is the relationship of alpha-1,3-glucan to Hc virulence
Wild type Hc colonies that express alpha-1,3-glucan are rough, clumped and virulent. Null mutants are smooth, dispersed, and not fully virulent
-this molecule may help prevent Hc from being recognized by the host immune system because it shields beta-glucan thus blocking Hc binding to dectin-1 a mammalian cell surface receptor for beta-glucan that is important in the innate immune response
Describe the role of the the calcium binding protein encoded by CBP1 in Hc virulence
-pCBP1 binds calcium and is express only in the yeast morphotype. Null mutants for CBP1 have greatly reduced virulence in mouse macs.
-may bind calcium and contribute to fungal nutrition
-may influence calcium mediated signaling processes in host cell
Describe the role of YPS3 gene/ Yps3 protein in Hc pathogenesis
-Yeast morphotype specific expression (YPS=yeast phase specific)
-possibly upreguated during infection via differentially stable transcripts
-strains that express YPS3 (all have it) are more thermotolerant and virulent, down regulation of YPS3 decrease virulence
-homology to mammalian EGF proteins which are important for signaling and adhesion, perhaps Yps3 modulates host intracellular signaling or promotes attachment to host cells/ extracellular matrix
Discuss 3 similarities between YPS3 of Hc and BAD1 of Bd
1. Both are only expressed in the yeast morphotype
2. Both proteins are found on the cell surface and are released into culture supernatant, the released protein binds back to the chitin in the fungal cell surface
3. Both share conserved regions including the N terminal signal sequence responsible for secretion and the C terminal EGF like domain
Discuss a major difference between Bd BAD1 and Hc YPS3
BAD1 is much bigger due to a larger internal region of tandem repeats with homology to Yersinia invasion protein
List 6 potential Hc virulence determinants
1. Avoidance of host oxidative antimicrobial defenses
2. Avoidance of host pH dependent defenses
3. Acquisition of iron
4. cell surface alpha-1,3-glucan
5. Calcium binding protein encoded by CBP1
6.YPS3 encoding Yps3
mneomic= Yes, Occasionally I can allow penetration
T/F Bd has a capsule
Describe Bd ploidy and nucleation
conidia are haploid and uninucleate, yeast are multinucleate
Describe the ecology of Bd
-poorly understood, few reported isolations
-fungus grows in microfoci of moist, rich soil with an acid pH, especially damp, wet areas around shorelines
Where are the majority of cases of Bd reported
What are the endemic regions?
North America
endemic regions include Southeast, South central and Midwestern states
WI is one of the few states where Bd is reportable
Hyperendemic regions include Vilas and Portage counties
note canine Bd occurs in high incidence near Eagle River
T/F there is a skin antigen test for Bd
Describe the 3 clinical forms of blastomycosis
1. acute pulmonary-flu like sxs, sometimes self limited
2. Chronic pulmonary- atypical pneumonia, indolent course
3. Disseminated infection- commonly skin, bone, genitourinary, can also involved visceral organs and CNS
Describe the 3 distinctive clinical forms of blastomycosis
1. Adult Respiratory Distress Syndrome (ARDS)- high fatality, rapidly progressive, need intensive Tx
2. Meningeal blastomycosis- difficult to Dx and Tx
3. Opportunistic blastomycosis- increasingly frequent, associated with steroids, transplantation, hematologic cancer, AIDS
What are the endemic regions of Paracoccidioidomycoses?
Highest incidence in Brazil but occurs in many parts of South America
-NOT common in Carribbean islands and Chile
-note that the distribution is changing due to agricultural frontiers
Describe environmental factors that increase the rate of Paracoccidioidomycoses
-High altitude
-Abundant rain
-rich vegetation after deforestation
-Acidic soils
-Colder and constant tempeatures
How is Paracoccidioides infection obtained
inhalation of conidia (chlamydoconidium)
What might explain the gender distribution of Paracoccidioides infections given that 15x more men get disease yet there is equal skin test reactivity
17-B-estradiol inhibits the switch from mold to yeast which prohibits pathogenicity
Why is a thoughout Pt Hx especially important when attempting to Dx Paracoccidioides infection
Can be dormant in latent period for up to 30 years, old travels are important!
Describe Paracoccidioides genetic variability
-3 distinct phylogeneic lineages S1, PS2 and PS3
-genographic distribution across south america
What are the three possible clincal manifestations of Paracoccidioides infection
1. subclinical infection
2. Acute juvenile form
3. Chronic Adult form
Describe subclinical Paracoccidioides infection
-health person but positive skin test
-person has CMI and TH1 IFN-g activated macrophages to ingest conidia and yeast
Describe the acute juvenile form of Paracoccidioides infection
-ages 10-20, equal gender distribution
-lost of Abs but this is useless
-infetion of lymph nodes, liver, spleen, bone marrow (reticuloendothelial system)
-poor prognosis
Describe the chronic adult form of Paracoccidioides infection
-from reactivation years after exposure
-90% of cases are males over 30
-lung involvement, mucosal oral and skin lesions
What is the infectious form of Paracoccidioides
Describe the hyphae and cell wall of Paracoccidioides mold form
-septate hyphae
-Cell wall has only B-glucan which promotes inflammatory cell recruitment and proinflammatory cytokines, promotes granuloma formation
Describe the unique yeast morphology of Paracoccidioides
"Pilot wheel" yeast with multiple narrow neck buds,
cell wall is predominately alpha 1-3 glucan which shields the yeast from the immune system
Describe the features of the TH1 response that are crucial for fighting Paracoccidioides infection
-activated macrophages
-Nitric oxide
How can Paracoccidioides be Dx'ed
-sxs may mimic other agenst so need to be careful
-can detect yeast form in clinical samples and culture positive 85% of active infeciton
-detect gp43 antigen in serum, urine,
-immunodiffusion, ELISA, estern
-monitor Ag titers, reduce w/ therapy
How is Paracoccidioides infection treated
-Tx for 12-24 months
-sulfa drugs
-Amphotericin B
Describe the role of the following Paracoccidioides virulence factors
Proteolytic enzymes
melanin like pigment
gp43-adhesion, may ulter binding and entry via phagocytoc cells
Proteolytic enzymes- facilitate tissue penetration
melanin- increases resistance to antifungal drugs
Describe how Paracoccidioides is similar to Hc
-facultative intracelluar parastive that leads to granulomas
-homologous genes and virulence factors (glucan, mold and yeast forms, mess with macrophages)
-Calcium binding protein
How does 17 B estradiol differentiallly effect Paracoccidioides and Hc
17B estradiol inhibits dimorphism in Paracoccidioides but facilitates it in Hc
What is unique about the "morphism" of Penicillium marneffei compared to all other Penicilliums
Penicillium marneffei is the only thermal dimorph, the rest are monomorphic
Describe the micro and macro scopic appearane of Penicillium species mold form
colony grows rapidly and is blue green with whtie border, reverse side is white and the hyphae are not pigmented
-micro- septate hyphae with penicillus (marge simpson) structure, flask shaped phialide producing a chain of round conidia
Where does Penicillium marneffei grow in the host
intracellulary in the macrophage
Where is Penicillium marneffei infection endemic
South east asia
Describe the unique morphology of Penicillium marneffei yeast
sausage shaped with central septum
How is infection with Penicillium marneffei obtained
assumed inhalation but unidentified environmental source
How do Penicillium marneffei yeasts divide?
fission NOT Budding like others
What animal might serve as a vector for Penicillium marneffei
bamboo rat
Describe how climate influenzes Penicillium marneffei incidence
seasonal distribution with tropical rainy season facillitating sporulation and aerosolizaiton
Describe the clinical presenation of Penicillium marneffei in HIV + and - pts
HIV+= acute onset
HIV- = chronic disease, HIV- usually have some other underlying disease
What sxs are associated with Penicillium marneffei
chronic cough, hepatosplenomegaly, weight loss, lymphadenopathy, fever, anemia
-mimics Tb and Histo
Describe the typical clinical presentation of Penicillium marneffei
-characteristic cutaneous lesions in 69-85% of cases
-lesions on face and upper trunk
-central necrotic umblilication (dry and crusty)
Where in the host might Penicillium marneffei be detected
mononuclear phagocytic system components (bone marrow, lymph nodes, liver, etc)
How is Penicillium marneffei infection Dx'ed
-Mp1p gene product is an immunogenic mannoprotein can test serum Ab and Ag (Ab higher in non HIV)
-can also test Ag levels in urine
(serum Ab is low in HIV but Ag is high pick test wisley)
What do Penicillium marneffei conidia bind upon entry into host
extracellular matrix components like fibronectin and laminin, alveolar macs then phagocytose conidia within 1 hr
What phase specific Penicillium marneffei genes are expressed during transition to yeast
cpeA and sodA
How is Penicillium marneffei infection treated
-fatal if untreated, need early Dx
-amphotericin for 2 weeks then oral itraconazole for 10 wks
-may need long term medication to prevent reccurance
How is Aspergillus classified?
Describe Aspergillus morphology
septate hyphae with circular vesicle, biseriate (metula and phialide) (the things that connect the conidia to the vesicle)
What hospital guidelines are used to prevent Aspergillus infection
-HEPA filters
-Positive pressure
-wet mopping
-Air exchange 12/h
-sealed rooms
-Pt masks
-no plants
How is infection with Aspergillus obtained
inhalation of conidia
list 3 common extrapullomonary sites of Aspergillus infection
ear (otomycosis)
cornea (keratomycosis)
Which species of Aspergillus is the most common cause of infections
Aspergillus fumigatus
List three risk factors for Aspergillus infection
-corticosteroid or other immunosuppressive Tx
-Chronic granulomatous disase
Describe how immunosupressive drugs affect host immunity
Leukopenia- low WBC counts
-Neutrophils- defective chemotaxsis, impaired phagocytosis, degranulation, adherence
-macrophages- inhibtion of pro-inflam cytos, decreased chemotaxsis, impaired phagocytosis
Describe invasive Aspergillosis
-associated with acute myeloid leukemia,
-inhalded spores colonize lungs, hyphae invade tissue and blood vessels leading to dissmeination
What is an aspergilloma
-fungus ball of mycelia, fibrin, and cellular debris
-occurs in prexisting cavity or site of lung damage (Tb pts, fibrotic lung disease)
-Tx requires directin infusion of anitfungals or surgical removal
What are the risk factors for otitis externa caused by Aspergillus and what species causes it
-commonly caused by Aspergillus niger
-swimming, water trapped in ear canal, trauma to ear canal, hot humid environemnt
What is the major risk factor for Aspergillus associated keratomycosis
-corneal trauma
-more common in the tropics
Describe ABPA
Allergic BronchoPulmonary Aspergillos
-hypersensitivity reaction in lung air space due to Aspergillus fumigatus
Describe the 5 stages of alveolar host defenses against Aspergillus conidia inhalation
1. Recognition of conidal cell wall components
2. Phagocytosis of conidia
3. Conidial swelling
4. Phagolysosome acidification and ROS= killing
5. Pro-inflammatory cytokines (TNFa)
Describe the significance of Aspergillus conidial swelling/ germination for the initiation of host immune response
Resting conidia are not recognized by the innate immune system. Swelling/ germination leads to a loss of the hydrophobic (Rodlet) layer which exposes the B-glucan and other antigens. B-glucan is an immunogen recognized by dectin-1 and initiates the response of dendrictic cells. This step is crucial if the host is going to be able to mount an effective innate response
What is the purpose of Aspergillus conidia Rodlet layer aka hydrophobic layer in terms of avoiding detecting by the host
The hydrophobic layer shields Aspergillus from pathogen recognition receptors by hiding the B-glucan. This layer is lost when the conidia begins to germinate (swell)
Describe the structural and role of neutrophil NETs in terms of immune response to Aspergillus infection
NETS= neutrophil extracellular traps
Made of nuclear DNA and fungicidal proteins. Entraps hyphae and possibly conidia, thought to prevent spreading of hyphae
What is the purpose of dectin-1 and what does it recognize in Aspergillus infection
Dectin-1 is a major host fungal innate immune receptor on macrophages. Dectin-1 recognizes B-1,3 glucan which is exposed when Aspergillus conidia swell and the rodlet layer is lost
What is the role of Aspergillus gliotoxin?
It is a secondary metabolite/ mycotoxin produced by Aspergillus that decreases host PMN function
Describe the consequences of Aspergillus angioinvasion
-hyphae infiltrate blood vessels
-activation of platelets
-hypoxic conditions
-vascular spread of infection
-note that even with vascular spread, only a low % of theses infections blood culture +
Describe the role of melanin in Aspergillus fumigatus pathogenesis
-gives resistance to ROS
-reduces phagocytosis and intracellular killing
How is aspergillosis Dx'ed (3 methods)
are there any drawbacks to these methods?
-microscopy/histology w/ staining using H&E and Silver, visualize host immune resposne and fungal tissue
-culture but problems with airborne plate contamination
-Non culture tests (radiological exam w/ halo sign of hemorrhage around fungal lesions, ELISA for galactomannan in serum, B glucan detecting in serum (not Aspergillus specific)
How is blastomycosis diagnosed
Presumptive vs. Confirmation
-confirmation by ID of fungus in culture or histopathology
-Presumptive Dx by visualizing the fungus in infected body fluid using KOH or calcofluor
Serology can be used but it is intensive or nonspecific, kits use the A antigen which is impure and ill-characterized, there is a better test using BAD-1
How can blastomycosis be treated
acute pulmonary?
chronic pulmonary? (meningeal vs. non meningeal)
acute pulmonary- azoles if stable, amphoteericin B is progressive
chronic pulmonary and disseminated- use azoles for nonmenigeal or non life threatening, use amphotericin for meningeal or life threatening (azoles don't get into CSF well and they are fungistatic, ampho is fugicidal)
opportunistic-Begin with ampho the long term with azoles
List 6 attributes of Pneumocystis that are atypical for fungi and resemble parasitic protozoa
1. morphology (cyst and trophozoite)
2. Relative fragility of cell wall
3. Susceptibility to antiparasitic agents
4. not susceptible to amphotericin B
5. Absence of ergosterol, presence of cholesterol and other sterols
6. Lack of an in vitro cultivable form
mnemonic Surely My Features Allow a Concise Explanation (Suceptibility, morphology, fragility, amphotericin, culture-not, ergosterol-not)
List 7 genetic/structural/ biochemical pieces of evidence that support the classification of Pneumocystis as a fungus and not a parasitic protozoa
-rRNA sequeces
-presence of EF3
-presence of thymidylate synthase and dihydrofolate reductase on two distinct genes
-presence of cell wall chitin
-presence of cell wall glucans esp. B glucan
-sensitivity to B glucan synthase inhibitors
-resemblance of cysts t oascomycetous fungal spores and formation of intracystic bodies resembling ascospores
Cystis commands great respect so glare enviously (chitin, cysts, glucan, rRNA, suceptibility, genes, elongation factor 3)
Describe the trophozoite form of Pneumocystis
2-5um often in groups, predominant morphological form in host, may represent vegetative form similar to yeasts
Describe the Cyst form of Pneumocystis
larger than trophozoites, may be generated from fusion of two haploid trophozoites followed by meiotic division within the cyst wall
What experimental challenges does the lack of a culture system for Pneumocystis cause (it is grown in animal lung homogenates from continuous in vivo passage via intratracheal infection)
-No way to obtain pure cultures
-No way to obtain fungal material (cells, protein, DNA) completely free of mammalian host material
Describe the exposure rates of Pneumocystis
exposure is assumed to be common based on:
-serologic studies indicate common exposure to the normal human population
-incidence of infection in immuno comp animals and AIDS pts indicates common exposure
What is the most common disease manifestation of Pneumocystis? What is the presumed infection route?
Pneumonia (PCP), presumed route of infection is respiratory
what is the infectious form of Pneumocystis?
inanimate environmental reservoir?
animal reservoir?
latent infection and reactivation?
consequences from sub-clinical infection?
unknown, we really don't know shit about this organism
Describe Pneumocystis host specificity
-evidence shows that organisms from one species cannot productively infect another
describe Pneumocystis antigenic differences among "strains"
-some antibodies raised against fungi from one host species do not recognize fungi from another host species
-antibodies that do cross react typically recognize molecules of different electrophoretic mobility in fungi from different species
List four phenotypic differences that occur among Pneumocystis "strains"
1. host specificity
2. antigenic differences
3. multi-locus enzyme electrophoresis (MLEE)
4. some morphologic differences
List three genotypic differences that occur among Pneumocystis "strains"
1. electrophoretic karyotypes (chromosome number and size)
2. DNA hybridization indicating level of homology for particular genes
3. DNA sequencing of specific genes
What species of Pneumocystis infects humans
Pneumocystis jirovecii
What two clinical syndromes are associated with Pneumocystis infection
1. diffuse interstitial pneumonia
2. dissemination
Describe Pneumocystis associated pneumonia
-diffuse interstitial pneumonia
-fungal cells generally found extracellularly
-trophozoites associated with damage to type I pneumocytes and cause loss of cells lining alveoli
-trophozoite proliferation, cyst formatino, and host response results in foamy eosinophilic exudate filling alveoli leading to honeycomb appearance
-gas exchange seriously compromised and pO2 dramatically decrease
-entire lung may be involved and significant damage can occur even in areas w/o fungus
T/F Pneumocystis usually infects health people
False, opportunistic infection virtually never seen in immunocompetent individuals
How is the importance of the CMI vs. humoral response difference for Pneumocystis than most other fungal pathogens
both CMI and humoral responses occur and both may contribute to protection. humoral resposne is usually non-protective in fungal infections. As with other infections, CMI is most important and loss of CMI is particularly responsible for disease suceptibility
Describe the epidemiology of Pneumocystis in relation to AIDS pts
70-80% of AIDS pts have PCP at least once
cause of death in 15-20% of AIDS pts
What is the gold standard of Pneumocystis Diagnosis
histopathologic demonstration of organism in biopsy, BAL fluid, sputum
Why is histopathologic demonstration of Pneumocystis in biopsy, BAL fluid, the gold standard of diagnosis i.e. why can't other methods be used?
-no culture method
-serology is of little benefit because nearly everyone is positive
-clinical signs and sxs are not specific
Describe the therapy used to Tx Pneumocystis
-TMP-SMX for Tx and prophylaxis but high incidence of toxicity and side effects esp. in AIDS pts
-drugs targeted at protozoan parasites
-steroids in acutely ill pts to stop threat to life from inflammatory response
What is the role of Pneumocystis MSG
-Major surface glycoprotein
-multiple antigenically distinct proteins (but only one at a time) and multiple partial distinct genes
-potential virulence determinant, immune avoidance mechanism
-proposed model for mechanism of variation
What are the three different ways fungi can interact with other organisms in their environment
1. saprobe/ saprophyte= free living
2. mutualist/ symbiont
3. parasite
Describe the role of sparophytic fungi in the ecosystem
-heterotrophic (use non-living organic material for food)
-important scavengers
-essential for recycling carbon, nitrogen, and mineral nutrients
Describe these three forms that mutulaistic fungi take
mycorrhizae- associateions of fungi with plant roots
lichen- associations of fungi with algae or cyanobacteria
endophytes- fungi that live inside the cells of plants
Describe fungal reproduction
-reproduce by means of spores, usually wind dissseminated
-both sexual (meiotic) and asexual (mitotic) spores may be produced, depends on conditions
Describe fungal cell walls
-composed of chitin
-protein fibrils
-Polyseaccharide subunits (mannans, glucans, chitin)
Describe the physical features that fungi prefer in their environment
-mesophillic (most) range 15-40 C
-more tolerant of low pH, tend to acidify environment
-do not require light for growth but most need it for sporulation
-water is essential
List 4 common characteristics of hyphae
1. polarized, apical growth
2. branching occurs behind the hyphal tip
3. septate or aseptate
4. aggregations of vesicles at the apices and growing regions (branch point or site of germ tube)
What's weird about fungal digestion
Fungi digest then ingest rather than ingest then digest like most animals. They secrete exoenzymes that break down food and then absorb the nutrients
List the suffixes applied to fungal
phlyum = mycota
class= mycetes
order= ales
family= aceae
What is fungal taxonomy based on?
reproductive structures
-sexual (teleomorph) and/or asexual (anamorph)
-taxonomy is based on teleomorph if known
There are four major phyla of fungi based on the their method of producing spores. List and describe them
What is the term used for fungi that have no known sexual state in their life cycle
1. Chytridiomycota- sexual and asexual spores. motile with posterior flagella
2. Zygomycota- sexual spores are thick walled
3. Ascomycota- spore borne internally in a sac called an ascus
4. Basidiomycota- spores borne externally on a club shaped structure called a basidium
Deuteromycetes or Fungi Imperfecti is the term used to describe fungi with no known sexual state
define each of these terms
mycosis- fungus invades the human tissue
mycotoxicosis- illness caused by eating the metabolites of a fungus but not the fungus itself
mycetismus- illness cuased by eating the fungus which contains toxins
mycoallergies- allergic reaction to fungi
List and describe the four possible locations of mycotic infections
1. superficial mycoses- infectionsof the hair shaft or dead outer layer of skin
2. Cutaneous mycoses- dermatophytes, infection of the skin hair and nails
3. Subcutaneous mycoses- chronic localized infections of the skin and subcutaneous tissues
4. Deep mycoses- aka systemic mycoses, fungal infections of the body caused by dimorphic fungal pathogens both real and opportunistic