Question
Type IV hypersensitivity reaction.
Answer
Type IV (delayed-type/cell-mediated) hypersensitivity is 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 (hence “delayed”).
Mechanism: on first exposure, antigen is processed and presented by antigen-presenting cells, generating a population of sensitized memory CD4+ Th1 cells (in the classical delayed-hypersensitivity form). On re-exposure to the same antigen, 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 and microbicidal capacity, and recruits further macrophages and lymphocytes to the site, producing a mononuclear cell (lymphocyte/macrophage)-rich inflammatory infiltrate rather than the neutrophilic/eosinophilic infiltrate of the immediate hypersensitivity types. A related subtype involves direct CD8+ cytotoxic T lymphocyte-mediated killing of target cells presenting the antigen on MHC class I.
Clinical examples:
- Tuberculin (Mantoux) reaction — the prototype, used diagnostically to detect prior sensitization to M. tuberculosis antigens.
- Granulomatous hypersensitivity — a chronic form seen when the antigen (e.g., persistent intracellular M. tuberculosis, M. leprae) cannot be cleared, leading to granuloma formation with caseation necrosis, epithelioid cells, and Langhans giant cells.
- Contact dermatitis — e.g., to nickel, poison ivy (urushiol), certain cosmetics/chemicals, where the chemical acts as a hapten, binding to skin proteins to form a complete antigen.
- 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) are an in-vitro correlate for tuberculosis sensitization.