Question
Type III hypersensitivity
Answer
Type III hypersensitivity (Immune complex-mediated hypersensitivity)
Mechanism: antigen combines with specific antibody (usually IgG or IgM) to form immune complexes in the circulation or at the site of antigen deposition. When these complexes are formed in moderate antigen excess, they are of intermediate size and are poorly cleared by the reticuloendothelial system, allowing them to deposit in tissues — commonly blood vessel walls, renal glomeruli, joints, and skin. Deposited immune complexes activate the complement system (via the classical pathway), generating anaphylatoxins (C3a, C5a) that recruit neutrophils to the site. Activated neutrophils attempt to phagocytose the complexes and release lysosomal enzymes and reactive oxygen species, causing local tissue damage/inflammation (vasculitis) — the damage is a bystander effect of the neutrophil response, not direct cytotoxicity against a specific cell.
Examples:
- Serum sickness — a systemic form, following administration of foreign serum/protein (or certain drugs), with immune complexes depositing in multiple sites (joints, kidneys, skin), causing fever, urticaria, arthralgia, and lymphadenopathy.
- Arthus reaction — a localized form, a local vasculitis reaction at the site of antigen injection in a previously sensitized (high-antibody-titre) individual.
- Post-streptococcal glomerulonephritis — immune complexes (streptococcal antigen-antibody) deposit in the renal glomerular basement membrane, causing glomerulonephritis.
- Systemic lupus erythematosus (SLE) — chronic immune-complex disease with DNA-anti-DNA complexes depositing in multiple organs (kidney, skin, joints).
- Rheumatoid arthritis — immune complexes (including rheumatoid factor) deposit in joints, contributing to synovial inflammation.
Diagnosis: demonstration of circulating immune complexes, low serum complement levels (C3/C4 consumption during active disease), and, on tissue biopsy, characteristic granular deposits of immunoglobulin/complement on immunofluorescence.