type III hypersensitivity
Summary
Type III hypersensitivity is an immune complex-mediated reaction in which antigen-antibody complexes (typically IgG or IgM) deposit in tissues, activate complement, and recruit neutrophils, causing local tissue damage. Classic examples include serum sickness, Arthus reaction, post-streptococcal glomerulonephritis, and systemic lupus erythematosus (SLE).
Detail
Pathophysiology: Antibodies (IgG/IgM) bind soluble antigens to form immune complexes that circulate and deposit in vascular walls, joints, skin, and glomeruli (especially in areas of high blood flow/turbulence like renal glomeruli). Deposited complexes activate the complement cascade (C3a, C5a), generating anaphylatoxins that recruit neutrophils. Neutrophils release lysosomal enzymes and reactive oxygen species, causing tissue damage—this is why it's often called an 'innocent bystander' reaction, since the damage is due to inflammatory mediators rather than direct cytotoxicity.
Timing: Reactions typically develop 1-3 weeks after antigen exposure (time needed for antibody production and immune complex formation), distinguishing it from Type I (immediate) and Type IV (delayed, 48-72 hrs) hypersensitivity.
Key clinical examples: - Serum sickness: Classic prototype, occurs after exposure to foreign proteins (e.g., antivenom, some drugs like penicillin). Presents with fever, urticaria, arthralgia, lymphadenopathy 1-2 weeks post-exposure. - Arthus reaction: Localized immune complex vasculitis after repeated antigen injection (e.g., vaccine booster), causing localized edema and necrosis. - SLE: Immune complexes (anti-dsDNA, anti-Smith) deposit in multiple organs including kidneys (lupus nephritis), skin, joints. - Post-streptococcal glomerulonephritis: Immune complexes deposit in glomerular basement membrane after streptococcal infection, causing hematuria, hypertension, edema. - Polyarteritis nodosa: Associated with HBV immune complexes. - Rheumatoid arthritis: Rheumatoid factor (anti-IgG antibody) forms immune complexes deposited in joints.
Lab findings: Low complement levels (C3, C4) due to consumption; can detect circulating immune complexes; renal biopsy may show granular immunofluorescence pattern ("lumpy-bumpy") from immune complex deposition, contrasting with the linear pattern seen in Type II (anti-GBM disease).
High-yield distinction: Unlike Type II hypersensitivity where antibodies target antigens fixed to cell surfaces, in Type III the antigen-antibody complexes form in circulation (or in situ) and then deposit in tissues, triggering complement-mediated inflammation.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Kaplan USMLE Immunology Lecture Notes
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