Question
Type 3 hypersensitivity.
Answer
Type III (immune-complex-mediated) hypersensitivity results from the formation and tissue deposition of antigen-antibody (immune) complexes, which activate complement and recruit neutrophils, causing local inflammation and tissue damage — distinct from Type II hypersensitivity, where antibody binds directly to a fixed tissue/cell-surface antigen.
Mechanism: soluble antigen combines with specific antibody in the circulation, forming immune complexes; complexes of a particular size (formed under conditions of moderate antigen excess) are not efficiently cleared by phagocytes and instead deposit in small blood vessels, joints, and glomeruli; deposited complexes activate the classical complement pathway, generating anaphylatoxins (C3a, C5a) that recruit and activate neutrophils, whose release of lysosomal enzymes and reactive oxygen species causes local tissue/vascular damage (vasculitis).
Clinical examples:
- Serum sickness — the prototype, following administration of foreign (heterologous) antiserum/protein, with fever, rash, arthralgia, and lymphadenopathy appearing ~7–10 days later.
- Arthus reaction — a localized Type III reaction at the site of a repeated antigen injection in a previously sensitized/hyperimmune individual.
- Systemic lupus erythematosus (SLE) — circulating immune complexes (e.g., anti-dsDNA/DNA complexes) deposit in the kidneys, skin, and joints, driving lupus nephritis and other manifestations.
- Post-streptococcal glomerulonephritis — immune complexes deposit in the glomerular basement membrane following streptococcal infection.
- Polyarteritis nodosa and other immune-complex vasculitides.
Laboratory correlates: reduced serum complement levels (C3, C4) during active disease (reflecting ongoing complement consumption), detectable circulating immune complexes, and, for SLE specifically, anti-dsDNA antibody titres.