Immunopathology Exam: SCID, Transplant OmpathStudy

MOUNT KENYA UNIVERSITY Academic Year: 2025/2026 School of Medicine — Pathology Department Programme: Bachelor of Medicine and Bachelor of Surgery, Year 3 Assessment: Continuous Assessment Test 2 — End of Semester 1 Unit Code: MBPA 3414 Unit Title: Immunopathology Date: 8th December, 2025 Time: 30 minutes Reg No: BMS/2023/60482 --- SECTION 1: SHORT ANSWER QUESTIONS (10 marks each) Question 1: "A 3-year-old child presents with recurrent bacterial infections, failure to thrive, and developmental delay. Immunological investigation reveals absent thymic shadow on chest X-ray, low lymphocyte count, and absent T cell proliferation to mitogens. However, B cell numbers appear normal. The child's parents are first cousins." a) Likely disorder + inheritance pattern (3 marks) Severe Combined Immunodeficiency (SCID) — most likely the autosomal recessive form (e.g., RAG1/RAG2 or ADA deficiency) Inheritance: Autosomal recessive (consistent with consanguinity — first-cousin parents) b) Primary immunological defect predisposing to infections (4 marks) Failure of T-cell development/maturation in the thymus (absent thymic shadow) → absent T-cell-mediated immunity Since T-cell help is required for normal B-cell antibody class-switching and response, even though B-cell numbers are normal, functional antibody responses are impaired Combined loss of cellular and humoral immune function leaves the child unable to fight bacterial, viral, fungal, and opportunistic infections Result: severe, recurrent, and often fatal infections from early infancy c) Two potential complications + justification (3 marks) Opportunistic infections (e.g., Pneumocystis jirovecii pneumonia, disseminated BCG/candidiasis) — due to absent T-cell surveillance against intracellular/opportunistic organisms Graft-versus-host disease (GVHD) from non-irradiated blood transfusions or maternal T-cell engraftment — because the infant cannot reject foreign (maternal/donor) T lymphocytes due to lack of functional immune rejection capacity --- Question 2: "A 35-year-old renal transplant recipient... graft dysfunction, rising creatinine, biopsy shows patchy interstitial fibrosis, tubular atrophy, arterial intimal thickening without significant acute inflammation, and negative immunofluorescence for C4d." a) Classify the rejection type + pathophysiology (4 marks) Chronic (cell-mediated) allograft rejection — specifically chronic allograft nephropathy/vasculopathy Negative C4d makes chronic antibody-mediated rejection less likely, pointing to a T-cell-mediated chronic process Pathophysiology: Repeated subclinical T-cell-mediated injury over time → chronic vascular injury with intimal smooth muscle proliferation (arterial intimal thickening) → progressive luminal narrowing, ischaemia, interstitial fibrosis, and tubular atrophy — a slow, indolent process rather than acute inflammatory rejection b) Why calcineurin inhibitors may paradoxically contribute + alternative mechanisms (3 marks) Calcineurin inhibitors (e.g., tacrolimus, cyclosporine) are directly nephrotoxic — cause afferent arteriolar vasoconstriction and chronic ischaemia, contributing to the same interstitial fibrosis/tubular atrophy pattern seen in rejection This makes it difficult to distinguish drug toxicity from chronic rejection histologically Alternative mechanisms: chronic subclinical cellular rejection, donor-specific antibodies below C4d detection threshold, recurrent original kidney disease, and hypertension-related vascular injury c) One therapeutic + one preventive strategy (3 marks) Therapeutic: Optimise/reduce calcineurin inhibitor dose or switch to a less nephrotoxic regimen (e.g., mTOR inhibitor such as sirolimus) Preventive: Regular protocol biopsies and monitoring of graft function/drug levels to detect subclinical rejection or toxicity early, allowing timely immunosuppression adjustment --- SECTION 2: LONG ESSAY QUESTION (20 marks) Question 1: "A middle-aged male presents with chronic nasal congestion, sneezing, watery eyes worsened by dust/pollen/pet dander; severe penicillin reaction (urticaria, bronchospasm within minutes); recurring hematuria and hypertension beginning two years after streptococcal throat infection; low serum C3, positive anti-GBM antibodies, proteinuria; biopsy shows glomerular hypercellularity and subepithelial immune complex deposits." a) Classify each condition by hypersensitivity type + mechanisms (10 marks) Allergic rhinitis (dust/pollen/pet dander) → Type I hypersensitivity IgE-mediated; allergen cross-links IgE bound to mast cells/basophils → degranulation → histamine, leukotrienes release → immediate vasodilation, mucus secretion, sneezing Penicillin reaction (urticaria, bronchospasm within minutes) → Type I hypersensitivity Penicillin acts as a hapten, binds host protein → IgE sensitisation → rapid mast cell degranulation on re-exposure → systemic anaphylactoid features Post-streptococcal glomerulonephritis-like picture (hematuria, hypertension, low C3, subepithelia