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Fungal species
Species, mechanisms
| Term | Definition |
|---|---|
| What fungal species are systemic pathogens and what are their characteristics? | Histoplasma (USA, Africa), coccidioides (west USA), talaromyces (SE Asia) -> microscopic saprotrophs -> high virulence -> inhaled airborne species, commonly invade macrophages asymptomatically |
| What fungal species are systemic opportunists and what are their characteristics? | Candida, Pneumocystis, Aspergillus -> low virulence -> take advantage of weakened host defence (immunocompromised) -> lung, paranasal sinuses, gut, baldder catheters, IV lines |
| What is the structure/transmission of Histoplasma capsulatum? | Dimorphic fungus in soil/bat droppings in USA/Africa -> environmental filamentous moulds release airborne spores -> inhaled by bats/humans in caves |
| What is the morphology of Histoplasma capsulatum? | 24 degrees -> multicellular filamentous mould w/ asexual spores -> 37 degrees -> unicellular spores germinate into budding yeast via DRK1/RYP1 kinases |
| How are Histoplasma capsulatum spores adapted? | Surface alpha-1,3-glucan not recognised by Dectin-1 PRR (beta-1,3/4-glucan), fungal hsp60 binds to macrophage CD11/18 for invasion, secretes protease-resistant Ca2+ bindign protein (CBP) -> facilitates fungal growth w/in macrophage vacuoles |
| How do Histoplasma invade macrophages? | Binds to DC VLA-5 R -> presented on DC MHC I -> stimulate DC IL-12 release -> CD4+ T cell differentiation into Th1 -> releases IFNgamma/TNFalpha -> macrophage activation -> yeast hsp6- binds to macrophage CD11b/CD18 R -> macrophage vacuole invasion |
| What are the effects of persistent Histoplasma infection? | Asymptomatic macrophage infection -> controlled by host T cells -> activate macrophages -> long-term granuloma formation -> persist for decades -> infection reactivates when host beomes immunocompromised |
| How is Histoplasma detected? | Dead Histoplasma Ag injected into skin -> delayed type IV hypersensitivity reaction (skin inflammation) via memory CD4+ T cells |
| How is Histoplasma treated? | Itraconazole -> inhibit 14-alpha-demethylase (prevent lanosterol conversion to ergosterol), amphotericin -> binds to PM ergosterol and create pore membranes to disrupt ion gradients |
| What is the evolution of Histoplasma infection? | Asymptomatic -> acute pulmonary (lung shadow inflammatory exudate w/ enlarged hilar lymph nodes) -> chronic pulmonary (fibrous tissue/calcification/cavitation) -> disseminated (widespread disease w/ inflammatory masses) |
| Where is Candida albicans found and its virulence factors? | Commensal yeast on moist mucosal surfaces (throat, gut, vagina) -> pseudohyphae (invade epithelium) -> biofilm formation (organisms embedded in sticky ECM) -> candidalysin (secreted 31 aa peptide cytolytic toxin) |
| What are the effects of candidalysin? | Damages epithelial cells -> chronic nail disfiguration, activates MAPK -> p38 -> c-Fos -> upregulates IL-1 |
| What are the types of Candida infection? | Oral candidiasis, vulvo-vaginitis, severe oral candidiasis, candidaemia, disseminated to eyes, liver, skin, spleen -> endophthalmitis (white fluffy retinal nodules) |
| How is Candida treated? | Prolonged anti-fungal drugs, correct underlying host defect (AIDS -> start anti-HIV treatment, stop immunosuppressants), caspofungin -> echinocandin (inhibit cell wall beta-1,3-glucan synthesis) |
| What type of fungus is Pneumocystis? | Obligate parasite -> coevolved w/ humans (genome contraction) -> lacks enzymes for aa synthesis/ergosterol, has enzymes for folic acid sytnehsis |
| How does Pneumocystis infect organisms and humans? | Preferential infection by species (jirovecii -> human, carinii -> rat) -> inhalation of airborne spores, children -> develop Ab by age 3 from early transient asymptomatic infection, adults -> no long-term colonisation -> reinfection in compromised host |
| How does Pneumocystis reproduce? | Asexual form -> haploid trophic binary fission, sexual -> 2 haploid gametes fuse -> meiosis -> mitosis -> sexual spore formation (cyst) -> temporariliy diploid, airborne spore tarnsmission |
| How does the host defend against Pneumocystis? | T cells rather than Ab |
| What are the consequences of Pneumocystis infection? | Pneumonia -> diffuse lung alveoli inflammation -> foamy protein-rich exudate (X ray shadowing/CT scan diffuse white), impaired gas diffusion (arterial hypoxaemia, dry cough, breathlessness, fever, weight loss) |
| How is Pneumocystis treated? | Cotrimoxazole (sulfamethoxazole + trimethoprim inhibits fungal folic acid synthesis), prenisolone corticosteroid short-term anti-inflammatory treatment (reduce PRR inflammatory response to fungal polysaccharides) |
| Where is Cryptococcus neoformans found, how does it infect organisms and what determines its virulence? | Environmental saprotrophic yeast abundant in bird droppings -> spores inhaled -> spreads from lung into circulation to CNS/brain, virulence determined by thick polysaccharide capsule |
| What are the consequences of Cryptococcus infection? | Impaired T-cell immunity, rare pneumonia, chronic meningo-encephalitis/hydrocephalus (progressively worsening headache, confusion, xcs CSF accumulation from impared reabsorption -> enalrged cerebral ventricles -> high ICP), coma |
| How is Cryptococcus treated? | Amphotericin (polyene) -> binds to PM ergosterol and creates pores to disrupt ion gradients, flucytosine (integrates into RNA -> inhbiit RNA synthesis, inhibits thymidylate synthetase -> inhibit DNA synthesis) |
| What are the types of infection for Aspergillus? | Allergic broncho-pulmonary aspergillosis (airway colonisation) -> aspergilloma (localised hyphae mass/aggregates colonising pre-existing TB lung cavity) -> invasive lung/paranasal sinus infection -> disseminated infection along arteries (no thrombosis) |
| What is the treatment for Aspergillus? | Amphotericin (polyene -> bind to PM ergosterol to create pores to disturb ion gradients), voriconazole (azole -> inhibit 14-alpha-demethylase lanosterol conversion to ergosterol) -> high fatality otherwise |
| How is Mucor transmitted? | Inhalation of airborne spores, direct wound contamination |
| What are the consequences of Mucor infection? | Mucormycosis -> rare but serious -> poorly controlled diabetes/leukaemia -> aggressive mould invasion via paranasal sinuses/lungs |
| How is Mucor treated? | Urgent surgery to remove dead tissue, IV amphotericin (polyene -> bind to PM ergosterol to create pores to disturb ion gradients) |
| What is the problematic treatment of Candida? | Candida can be problematic after treatment w/ broad-spectrum Abx (opportunistic pathogen after microbiome clearance) |
Created by:
vykleung
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