Type IV Hypersensitivity Reaction (Cell-mediated / Delayed-type reaction)
Type IV hypersensitivity is a T-cell mediated immune response, not involving antibodies, that leads to tissue injury.
- Also called delayed-type hypersensitivity (DTH) because reactions develop 24–48 hours after exposure.
Key Features
- Mediated by: Sensitized T lymphocytes (CD4+ and CD8+ T cells).
- Time course: Delayed onset (24–48 hours after antigen exposure).
- No antibodies or complement involvement.
Types of Type IV Reactions
- 1 Delayed-type hypersensitivity (DTH)
- Mediated by: CD4+ T helper (Th1) cells.
- Mechanism:
- Antigen-presenting cells (APCs) present antigen to Th1 cells → activation and cytokine release (e.g., IFN-γ, TNF-α).
- Cytokines recruit and activate macrophages → local tissue inflammation and damage.
- Examples:
- Tuberculin skin test (Mantoux test) for TB.
- Contact dermatitis (e.g., poison ivy, nickel allergy).
- Granulomatous inflammation (e.g., TB, sarcoidosis).
- 2 Direct cytotoxicity
- Mediated by: CD8+ cytotoxic T lymphocytes (CTLs).
- Mechanism:
- Recognize antigen presented on MHC I of target cells → release perforin and granzymes → induce apoptosis.
- Examples:
- Type 1 diabetes mellitus (β-cell destruction).
- Graft rejection.
- Some viral hepatitis cases.
Pathogenesis (DTH)
- 1 Sensitization phase (initial exposure):
- Antigen processed by APCs → presented to naive CD4+ T cells → differentiation into Th1 cells.
- 2 Elicitation phase (re-exposure):
- Memory Th1 cells recognize antigen → release IFN-γ, TNF-α → macrophage activation → local tissue destruction.
Histopathology
- Perivascular T cell and macrophage infiltrates.
- Edema and fibrin deposition.
- Granuloma formation (if chronic).
Diagnostic Test
- Patch test: Used for contact dermatitis; allergen applied on skin → observe delayed reaction.
Treatment
- Corticosteroids (to reduce inflammation).
- Immunosuppressive therapy (in severe cases).