Type III Hypersensitivity Reaction (Immune-Complex Reaction
Type III hypersensitivity is an immune-mediated reaction caused by antigen-antibody (immune) complexes, which deposit in tissues and trigger inflammation and tissue injury through complement activation and recruitment of inflammatory cells.
Key Features
Mediated by: IgG (mainly) or IgM antibodies.
Antigens: Can be exogenous (microbial, drugs) or endogenous (self-antigens).
Complexes: Form in circulation and deposit in various tissues (vessels, joints, glomeruli).
Pathogenesis
1 Immune complex formation
Soluble antigen combines with antibody in circulation → formation of small or intermediate-size complexes.
2 Deposition of complexes
Complexes circulate and deposit in tissues, especially:
- Blood vessel walls (vasculitis).
- Renal glomeruli (glomerulonephritis).
- Synovial membranes (arthritis).
Predisposing factors:
- Increased vascular permeability.
- High blood pressure.
- Turbulent blood flow.
3 Inflammatory reaction
Deposited immune complexes activate classical complement pathway → generation of C3a, C4a, C5a (anaphylatoxins).
C5a: strong neutrophil chemotactic factor → neutrophil recruitment and activation.
Release of lysosomal enzymes and reactive oxygen species → tissue damage.
Clinical Examples
Local vs Systemic Reaction
Systemic immune complex disease
- Complexes form in circulation → multiple organ involvement (e.g., serum sickness).
Localized immune complex disease (Arthus reaction)
- Complexes form at site of antigen injection.
- Local edema, hemorrhage, necrosis, and thrombosis.
Morphological Features
- Fibrinoid necrosis of vessel walls.
- Neutrophilic infiltrate in and around vessels.
- Granular immunofluorescence (deposits of Ig and complement).
Diagnostic Tests
- Immunofluorescence microscopy: detects immune complex deposits (e.g., granular pattern in glomeruli).
- Serologic tests: decreased complement levels (due to consumption), circulating immune complexes.
Treatment
- Remove or avoid offending antigen.
- Anti-inflammatory drugs (e.g., corticosteroids).