--- MEDICAL VIROLOGY & MYCOLOGY MOUNT KENYA UNIVERSITY — MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 4 OF 4 --- INTERFERON MECHA
--- MEDICAL VIROLOGY & MYCOLOGY MOUNT KENYA UNIVERSITY — MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 4 OF 4 --- INTERFERON MECHANISM Section B essay question in 2021/2022 — must know. What interferons are - Glycoproteins produced by virus-infected cells - Part of innate immune response - Act on neighboring cells to prevent viral spread How interferons help virus-infected cells fight infection - Virus infects a cell and triggers that cell to produce interferons alpha and beta - Interferons are released and bind to receptors on neighboring uninfected cells - This binding activates JAK-STAT signalling pathway in neighboring cells - Neighboring cells produce antiviral proteins — including protein kinase R and RNase L - Protein kinase R: inhibits protein synthesis in infected cells, preventing viral replication - RNase L: degrades viral RNA - Neighboring cells also upregulate MHC class I molecules — enhancing recognition by cytotoxic T cells - NK cells are also activated by interferons to kill infected cells - Net effect: limits viral spread to surrounding cells Types of interferons - Interferon alpha and beta: produced by virus-infected cells, act on neighboring cells - Interferon gamma: produced by T cells and NK cells, activates macrophages --- ATTENUATED VACCINES — HOW THEY PROTECT Section B essay question — child born in Muranga vaccinated with attenuated vaccine. What an attenuated vaccine is - Contains live but weakened form of the pathogen - Weakened by repeated passage in laboratory conditions - Cannot cause full disease in healthy individual How it protects - Attenuated organism enters body and replicates at low level - Replication stimulates both humoral immunity — antibody production - And cell-mediated immunity — T cell activation - B cells produce specific antibodies against the pathogen - Memory B cells and memory T cells are formed - On exposure to real pathogen, memory cells mount rapid and strong immune response - Pathogen is eliminated before disease develops Advantages over inactivated vaccines - Stronger and longer lasting immunity - Often single dose sufficient - Stimulates both arms of immune system Disadvantage - Risk of reversion to virulent form — especially OPV --- TRUE PATHOGENIC FUNGI VS OPPORTUNISTIC FUNGI Section B essay question in 2021/2022. True pathogenic fungi - Cause disease in both healthy and immunocompromised individuals - Have specific virulence mechanisms - Geographically restricted — endemic mycoses - Examples: Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis - Infection acquired by inhalation of spores from environment - Primary infection in lungs even in healthy persons Opportunistic fungi - Cause disease ONLY or mainly in immunocompromised individuals - Part of normal flora or ubiquitous in environment - Have low inherent virulence - Examples: Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Mucor species - Take advantage of defective host defenses General consequences to human host - Superficial infections: cosmetic only, no systemic effect - Cutaneous infections: discomfort, disfigurement, secondary bacterial infection - Subcutaneous infections: chronic granulomatous disease, tissue destruction, lymphatic spread - Systemic infections: life threatening, multi-organ involvement, high mortality in immunocompromised --- MYCETOMA — PATHOGENESIS AND LABORATORY DIAGNOSIS Essay question in 2017/2018 — high priority. Causative agents - Eumycetoma: caused by true fungi — Madurella mycetomatis, Pseudallescheria boydii - Actinomycetoma: caused by bacteria — Nocardia species, Actinomadura species Pathogenesis - Traumatic inoculation of organism into skin — thorn prick, splinter, walking barefoot - Organism establishes in subcutaneous tissue - Slowly progressive granulomatous inflammation - Formation of grains/granules — aggregates of organism - Sinus tracts form and open to skin surface, discharging grains - Spreads to involve deeper tissues, muscle, bone - Bone destruction in advanced disease - Does NOT spread via lymphatics or bloodstream — remains local Clinical features - Painless swelling of affected area — usually foot - Draining sinus tracts - Discharge containing grains — color depends on organism - Deformity of affected part Laboratory diagnosis - Macroscopic: examine grains from discharge — color, size, texture - Microscopy: KOH preparation of grains, Gram stain - Culture: Sabouraud agar — identify organism - Histopathology: tissue biopsy shows granuloma with grains - Imaging: X-ray to assess bone involvement Eumycetoma vs Actinomycetoma comparison - Eumycetoma: fungal, wide grains, does not respond to antibiotics, responds to antifungals and surgery - Actinomycetoma: bacterial, thin filaments in grains, responds to antibiotics — sulfonamides, streptomycin --- DERMATOPHYTOSIS — FIVE TYPES Essay question in mycology CAT — discuss five types. Tinea pedis — Athlete's foot - Site: toe webs, soles of feet - Features: itchy, white flaky patches, inflammation, skin fissures, stinging - Causes: wearing tight shoes, sweating, keeping feet wet - Agent: Trichophyton rubrum most common Tinea capitis — Scalp ringworm - Site: scalp hair and skin - Features: scaly patches, hair loss, blister-like lesions on scalp - Common in children - Agent: Microsporum canis from animals, Trichophyton tonsurans in humans - Zoophilic agents cause acute inflammation Tinea corporis — Ringworm of the body - Site: skin of trunk, limbs, face - Features: circular dry scaly pruritic lesion with raised borders - 2-year-old girl with rash from pet cat: Microsporum canis - KOH preparation shows branching septate nonpigmented hyphae: dermatophytosis Tinea cruris — Jock itch - Site: groin, inner thighs - Features: itchy, red, ring-shaped rash - More common in males Tinea unguium — Nail infection / Onychomycosis - Site: finger and toe nails - Features: thickened, discolored, brittle nails - Agents: Epidermophyton floccosum, Trichophyton rubrum, Trichophyton mentagrophytes - NOT Microsporum canis — does not infect nails General treatment of dermatophytoses - Topical: clotrimazole, miconazole - Systemic: griseofulvin, terbinafine, itraconazole - Griseofulvin: classic drug for dermatophytes --- LABORATORY DIAGNOSIS OF SYSTEMIC MYCOSES Essay question in 2017/2018 — full detail. Specimen collection - Respiratory: sputum, BAL, bronchial washings - Blood: for disseminated disease - CSF: for meningitis — Cryptococcus - Tissue biopsy: for definitive diagnosis - Urine: antigen detection for Histoplasma Macroscopic examination - Colony morphology on Sabouraud agar - Color, texture, growth rate, surface appearance Microscopy - KOH wet mount: dissolves background material, reveals fungal structures - India ink: negative stain for Cryptococcus capsule - Calcofluor white: fluorescent, binds chitin in fungal cell walls - PAS stain: fungal cell wall stains red - Gram stain: Candida stains gram positive Culture - Sabouraud dextrose agar: standard medium, pH 4-6 - Incubate at both 25°C and 37°C — to demonstrate dimorphism - Histoplasma: very slow, weeks to months - Confirm dimorphic fungi by conversion to tissue form in vitro - OR by detection of species-specific antigens or DNA sequence analysis Serology - Latex agglutination: Cryptococcus polysaccharide capsular antigen — highly specific - Complement fixation: Histoplasma and Coccidioides - ELISA: antigen and antibody detection Molecular methods - PCR: species-specific DNA detection - DNA sequence analysis: confirmation of dimorphic fungi --- NORMAL CELL VS TUMOR/CANCER CELL Essay question in CAT 2018/2019. Normal cells - Undergo apoptosis when programmed - Controlled replication — respond to growth signals - Do not invade surrounding tissue - Maintain normal cellular structure - Undergo contact inhibition — stop dividing when touching other cells - Have normal cell cycle checkpoints - Require growth factors to divide