Question
Classify Hyper sensitivity reactions. Write in detail about type IV Hypersensitivity
Answer
Classification of hypersensitivity reactions (Gell and Coombs classification):
- Type I — Immediate/anaphylactic, IgE-mediated (e.g., anaphylaxis, allergic rhinitis, asthma).
- Type II — Antibody-mediated cytotoxic, IgG/IgM against fixed cell-surface antigens (e.g., autoimmune haemolytic anaemia, Goodpasture syndrome).
- Type III — Immune-complex-mediated (e.g., serum sickness, SLE).
- Type IV — Delayed-type, cell-mediated (T-cell mediated).
Type IV (delayed-type/cell-mediated) hypersensitivity in detail Unique among the hypersensitivity reactions in being antibody-independent, mediated instead by sensitized T lymphocytes, and characteristically taking 24–72 hours to develop after antigen re-exposure.
Mechanism: on first exposure, antigen is processed and presented by antigen-presenting cells, generating sensitized memory CD4+ Th1 cells. On re-exposure, these sensitized Th1 cells recognize antigen presented on MHC class II, become activated, and secrete cytokines — notably IFN-γ, which activates macrophages, enhancing their phagocytic/microbicidal capacity, and recruits further macrophages and lymphocytes, producing a mononuclear cell (lymphocyte/macrophage)-rich inflammatory infiltrate. A related subtype involves direct CD8+ cytotoxic T lymphocyte-mediated killing of target cells presenting antigen on MHC class I.
Clinical examples: Tuberculin (Mantoux) reaction — the prototype; granulomatous hypersensitivity — a chronic form when the antigen (e.g., persistent intracellular M. tuberculosis, M. leprae) cannot be cleared, leading to granuloma formation with caseation necrosis; contact dermatitis — to nickel, poison ivy, cosmetics/chemicals; graft rejection (acute cellular rejection) and certain drug reactions.
Laboratory demonstration: the tuberculin skin test (Mantoux) and patch testing (for contact allergens) are the classical in-vivo tests; interferon-gamma release assays (IGRAs) provide an in-vitro correlate for tuberculosis sensitization.