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34 Cards in this Set
- Front
- Back
How is coccidioides classified
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haploid ascomycete
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Name two species of coccidioides and describe their relationship in terms of distribution, mophology, and clincal presentation
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C. immitis-San Joaquin Valley of CA
C. posadasii- SW USA, Mexico, Central America, South America identical morpology and clinical presentation |
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Coccidioides is a thermal dimorph. Describe its two states
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25C saprobic phase- mycelia/mold, multinucleate arthorconidia alternating with empty cells
37C parasitic phase- spherules, uninucleate endospores |
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What role does CO2 and 17-B estradiol play in Coccidiodes phase switching?
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CO2 and 17B estradiol favor the spherules endospore form (explains higher incidence in pregnant women)
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Describe the ecological niche of Coccidioides
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Lower Sonoran life zone
arid climate, litte rain, alkaline soil, hot summers, winters with few freezes |
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What is the infectious form of Coccidioides
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arthroconidia
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Describe stage I of Cocci spherulation
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-less than 24 hrs
-arthroconidia enlarge and become uninucleate |
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Describe stage II of Cocci spherulation
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24-28hrs
-arthorconidia become spherules -Spherules undergo isotropic growth -Synchronous nulear division produces multinucleate spherule |
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Describe Stage III of Cocci spherulation
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-72-96 hrs
-nuclear division ceases -segementation to form uninucleate endospores -mature sperule |
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Describe stage IV of Cocci spherulation
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-spherule rupture
-200-300 endospores within each spherule capable of developing into a spherule |
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What is the role of the BGL2 gene in Cocci pathogenesis
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-encodes B glucosidase
-expressed only in parasitic phase with highest expression during isotropic growth -Thought to cleave B 1-3 glucan polymers to allow for cell wall expansion during isotropic growth |
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What would be the consequence to Cocci pathogenesis of a BGL2 deletion
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-slowed spherule development
-attenuated virulence |
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List the 4 major virulence factors of Cocci
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1. Spherule Outer Wall (ECM)
2. Spherule Outer Wall Glycoprotein (SOWgp) 3. Extracellular Proteinases 4. Urease |
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Describe the role of Cocci spherule outer wall matrix in pathogenesis
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-composed of lipids and proteins
-imapirs direct PMN contact with spherules |
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Describe the role of Cocci SOWgp in pathogenesis
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-localized to spherule cell surface
-functions as an adhesion (laminin, fibronectin, collagen) -expressed during isotropic growth |
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What would the consequnce of a SOWgp deletion be to Cocci pathogenesis
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-decreased spherule binding to host ECM protiens
-attenuated virulence, TH1 (what you want) rather than TH2 (ineffective) response is illicited |
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Describe the role of MEP1 Metalloproteinase in Cocci pathogenesis
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-Peak expression during endosporulation, minimal during isotropic growth
-Functions as an immune evasin by digesting SOWgp on endospores |
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What would the consequnce of a MEP1 deletion be to Cocci virulence
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-MEP1 digests spherule outer wall glycoprotein
-increase in SOWgp on the cell surface of endospores -increased suceptibility to phagocytosis Cocci must establish a balance between expression of SOWgp to be able to bind to ECM but digestion of it to avoid the immune system |
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Describe the role of urease in Cocci pathogenesis
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-Encoded by URE gene which is expressed in both mycelia and sperules
-released following spherule rupture -enhances virulence |
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Describe the role and efficacy of neutrophils in host response to Cocci infection
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-first cell to reach site of infx, arothroconidia and endospore stimulate chemotaxis
-phagocytosis of arthroconidia and endospores but <20% killed -NO phagocytosis of spherules because of size and SOW complex |
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Describe the role and efficacy of non-T cell stimulated macrophages/ monocytes in host response to Cocci infection
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-phagocytosis of arthroconidia and endospores (NOT spherules) but only 1-25% killed
-anthroconidia and endospores that survive become mature spherules -there is inhibtion of phagolysosome fusion |
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Describe the role and efficacy of natural killer cells in the host immune response to Cocci infection
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kill arthorconidia and young spherules
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What is the only innate immune response element that can kill Cocci spherules
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natural killer cells but even then it's only the young ones. Neuts and monos/ naieve macs cannot!
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Describe the role and efficacy of T-lymphocytes in host response to Cocci infection
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-crucial for control and defense
-those with strong Type IV HS Rxn have Asx or subclinical Infx -those with weak Type IV HS have chronic or disseminated infection |
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What is the main/ crucial function of T-lymphocytes in host response to Cocci infection
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The T-lymphs of the adaptive immune response stimulate macrophages with IFN-g which helps the macs kill arthorconidia and endospores
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T/F Cocci spherules can be phagocytosed
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false, their size and SOW prevent phagocytosis by either neuts or macs
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When is the peak incidence of Cocci infection
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late summer and early fall due to dry soil, airborne arthroconidia in dust
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T/F most Cocci infections are problematic
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False 50-67% are asymptomatic
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What two classificaitons of disease are cause by Cocci
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pulmonary, extrapulmonary
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Describe the pulmonary presenation of Cocci
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-Pneumonia
-Fever, cough, chest pain, fatigue, dyspnea, headahce, rash, eosinophilia -chest imaging with inflitrates/ consolidation, Hilar LAD, pleural effusion, pumonary nodule, cavity, fibrovacitary |
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Describe the Extrapulmonary/ disseminatied disease cause by Cocci
Risk factors? |
-any organ but skin is most common follwed by CNS and bone, less common include eyes, larynx, heart (endocarditis), genitounirnary (prostate), joint (septic arthritis)
risk factors- non-white ethnicity, male or pregnant female, extreme of age, immunocompromised |
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How can Cocci be Dx'ed
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-sputum or tissue staining with KOH, calcofluor, H&E, Silver, PAS
-NOT gram stain -culture w/ LPCB prep -confirm with DNA probe test -serological test (tube precipitin TP IgM test) -Complement fixation (CF IgG test), antigen is chitinase, look for improved titer |
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Describe the Tx for Cocci
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Azoles
Amphotericin |
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Why must a the lab always be warned if a sample is suspected to contain Cocci
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-Considered a select agent with bioterrism potential but this is a questionable classification
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