Question
Classify hypersensitivity. Describe the pathogenesis of each one of them with examples. Draw diagrams wherever necessary (1+11+3)
Answer
Classification of hypersensitivity (Gell and Coombs classification):
- Type I — Immediate/anaphylactic, IgE-mediated.
- Type II — Antibody-mediated cytotoxic.
- Type III — Immune-complex-mediated.
- Type IV — Delayed-type, cell-mediated.
Type I (immediate/anaphylactic) hypersensitivity IgE-mediated; on first exposure, susceptible (atopic) individuals produce allergen-specific IgE, which binds via its Fc portion to FcεRI receptors on mast cells/basophils (sensitization). On re-exposure, allergen cross-links adjacent IgE molecules, triggering degranulation — release of preformed mediators (histamine, tryptase) and newly synthesized mediators (leukotrienes, prostaglandins, PAF) — causing vasodilation, increased vascular permeability, bronchospasm, and increased mucus secretion within minutes. A late-phase reaction follows 4–8 hours later, driven by recruited eosinophils/neutrophils. Examples: anaphylaxis, allergic rhinitis, bronchial asthma, urticaria. [Diagram: sensitization phase — allergen → plasma cell → IgE → binds FcεRI on mast cell; effector phase — repeat allergen exposure → cross-links IgE → degranulation → mediator release.]
Type II (antibody-mediated cytotoxic) hypersensitivity IgG/IgM antibody binds directly to antigen on a fixed cell-surface or tissue matrix component, activating complement (leading to direct cell lysis via the membrane attack complex, or opsonization for phagocytic destruction) or mediating antibody-dependent cellular cytotoxicity (ADCC) via NK cells. Examples: autoimmune haemolytic anaemia, Goodpasture syndrome (anti-GBM antibody), haemolytic disease of the newborn (Rh incompatibility), Graves’ disease (a variant — stimulating rather than destructive antibody against the TSH receptor). [Diagram: antibody bound to antigen on target cell surface → complement activation → MAC formation → cell lysis; or Fc receptor-mediated phagocytosis.]
Type III (immune-complex-mediated) hypersensitivity Soluble antigen combines with antibody in the circulation, forming immune complexes that deposit in small blood vessels, joints, and glomeruli (particularly complexes formed in moderate antigen excess); deposited complexes activate complement, generating anaphylatoxins (C3a, C5a) that recruit neutrophils, whose enzyme release causes local vasculitis/tissue damage. Examples: serum sickness, Arthus reaction, systemic lupus erythematosus, post-streptococcal glomerulonephritis. [Diagram: antigen-antibody complex formation in circulation → deposition in vessel wall → complement activation → neutrophil recruitment → vasculitis.]
Type IV (delayed-type/cell-mediated) hypersensitivity Antibody-independent, mediated by sensitized T lymphocytes, taking 24–72 hours to develop. Sensitized memory CD4+ Th1 cells recognize antigen on re-exposure, secrete IFN-γ, activating macrophages and recruiting further inflammatory cells, producing a mononuclear infiltrate. A related subtype involves direct CD8+ cytotoxic T-cell-mediated killing. Examples: tuberculin (Mantoux) reaction, contact dermatitis, granulomatous hypersensitivity (tuberculosis, leprosy), graft rejection. [Diagram: sensitized Th1 cell recognizes antigen-MHC II complex on APC → releases IFN-γ → macrophage activation → mononuclear inflammatory infiltrate.]