immune complex

Immune complexes form when antibodies (typically IgG or IgM) bind soluble antigens in the circulation. Normally, these complexes are cleared by the mononuclear phagocyte system (spleen, liver) via complement receptor-mediated mechanisms (CR1 on erythrocytes helps transport complexes to the liver/spleen for clearance). However, when there is antigen excess, complement deficiency, or impaired clearance, immune complexes can deposit in small vessel walls, glomerular basement membranes, joints, and skin.

Deposited immune complexes activate the classical complement pathway, generating C3a and C5a (anaphylatoxins) that recruit neutrophils. Neutrophils attempt to phagocytose the complexes but release lysosomal enzymes and reactive oxygen species, causing local tissue damage—this is the basis of Type III hypersensitivity reactions.

Key clinical examples: - Serum sickness: classic prototype, occurs ~1-2 weeks after exposure to foreign protein (e.g., antivenom), presents with fever, urticaria, arthralgia, lymphadenopathy - Arthus reaction: localized immune complex reaction at injection site - Post-streptococcal glomerulonephritis: immune complexes deposit in glomeruli causing nephritic syndrome - Systemic lupus erythematosus: anti-dsDNA immune complexes deposit in kidneys, skin, joints, causing lupus nephritis and malar rash - Polyarteritis nodosa: associated with HBsAg immune complexes - Henoch-Schönlein purpura: IgA immune complex deposition - Cryoglobulinemia: associated with Hepatitis C

Lab findings include low complement levels (C3, C4) due to consumption, and detection of circulating immune complexes. Histology often shows granular deposits on immunofluorescence (as opposed to linear deposits seen in Type II reactions like Goodpasture syndrome).

Treatment often involves removing the inciting antigen, immunosuppression (corticosteroids), and managing end-organ damage (e.g., ACE inhibitors for proteinuria in glomerulonephritis).