Medicine & USMLE

Type 3 Hypersensitivity Reactions

Hypersensitivity Reactions
  1. Type 1 Hypersensitivity Reactions
  2. Type 2 Hypersensitivity Reactions
  3. Type 3 Hypersensitivity Reactions
  4. Type 4 Hypersensitivity Reactions


Type III Hypersensitivity Reactions (T3HSR) are undesired immune responses caused by the deposition of circulating immune complexes. These immune complexes are formed when antibodies bind circulating antigens, forming a clump of antibodies and antigens. Once these immune complexes are produced, they can deposit along the walls of the bloodstream. After depositing, the antibodies in the immune complex activate the complement system via the classical pathway, which recruits neutrophils to cause damage.  High-yield examples of Type III hypersensitivity to know include serum sickness, the Arthus reaction, Henoch-Schonlein purpura, Polyarteritis nodosa, Poststreptococcal glomerulonephritis, and the manifestations of lupus nephritis and vasculitis in lupus. 

Key Points

  • Type 3 HSR
    • lupus Undesidred Undesired immune response mediated by immune complexes
      • Immune complexes are clumps of circulating antibody (IgG or IgM) bound to circulating antigens, which deposit along vessel walls
    • Antibodies in complexes cause Classical Complement Activation
      • Downstream complement activation attracts Neutrophils
        • Activated neutrophils cause inflammation
    • Examples
      • Serum sickness
        • Circulating antigen from serum-containing drugs (e.g. antitoxins) or drugs themselves (serum sickness-like reaction, e.g. penicillin)
        • Develops 1-2 weeks after administration
        • Presents with arthralgia, proteinuria, fever, and lymphadenopathy
      • Arthus reaction
        • Circulating antigen usually from vaccines
          • May cause people to feel sick after vaccination
        • Develops 4-12 hours after administration
        • Localized pain, swelling, induration, necrosis around injection site
      • SLE nephritis
        • Immune complexes responsible for vasculitis/lupus nephritis
      • Poststreptococcal glomerulonephritis (PSGN)
      • Polyarteritis nodosa
      • HSP (Henoch-Schonlein purpura)