Immunology and Immunopathology
Overview
This domain tests the mechanisms of immune-mediated disease and the laboratory tests used to classify them: complement, hypersensitivity reactions, autoantibody profiles, immunodeficiency, and transplant rejection.
Core rules
- Hypersensitivity: type I IgE-mediated immediate, type II antibody against fixed antigen, type III immune complex, type IV T-cell mediated delayed.
- Complement: classical pathway via C1q and IgG/IgM, alternative via microbial surfaces, lectin via mannose-binding lectin; low C3/C4 with active urinary sediment suggests lupus nephritis.
- Autoantibodies: ANA is sensitive but not specific; anti-dsDNA and anti-Sm are specific for systemic lupus. Anti-CCP is more specific than rheumatoid factor. c-ANCA targets proteinase-3 (granulomatosis with polyangiitis); p-ANCA targets myeloperoxidase (microscopic polyangiitis, eosinophilic GPA).
- Transplant rejection: hyperacute is preformed antibody against donor HLA, acute cellular is T-cell mediated, antibody-mediated shows C4d deposition and donor-specific antibodies, chronic shows graft vasculopathy and fibrosis.
- Coombs: direct detects antibody on the patient's red cells; indirect detects antibody in serum.
Worked example
A patient has hematuria, proteinuria and crescentic glomerulonephritis with no immune deposits on immunofluorescence, plus a positive c-ANCA. Reasoning: pauci-immune crescentic disease with PR3-ANCA supports granulomatosis with polyangiitis. Anti-dsDNA and complement would instead point to lupus nephritis, which shows full-house immunofluorescence. Therapy is immunosuppression with cyclophosphamide or rituximab plus steroids.
Traps
Treating a positive ANA as diagnostic of lupus. Confusing c-ANCA and p-ANCA targets. Forgetting that C4d deposition defines antibody-mediated rejection.