Hypersensitivity Types

Four types (ABCD): Anaphylactic and Atopic (type I), AntiBody-mediated (type II), Immune Complex (type III), Delayed (cell-mediated, type IV). Types I, II, and III are all antibody-mediated.

  • Type I hypersensitivity
    • Anaphylactic and atopic—two phases:
      • Immediate (minutes): antigen crosslinks preformed IgE on presensitized mast cells → immediate degranulation → release of histamine (a vasoactive amine) and tryptase (a marker of mast cell activation).
      • Late (hours): chemokines (attract inflammatory cells, eg, eosinophils) and cytokines (eg, leukotrienes) from mast cells → inflammation and tissue damage.
    • First (type) and Fast (anaphylaxis).
    • Test: skin test or blood test (ELISA) for allergen-specific IgE.
    • Example: Anaphylaxis (eg, food, drug, or bee sting allergies)
  • Type II hypersensitivity
    • Antibodies bind to cell-surface antigens → cellular destruction, inflammation, or cellular dysfunction.
    • Cellular destruction—cell is opsonized (coated) by antibodies, leading to either:
      • Phagocytosis and/or activation of complement system.
      • NK cell killing (antibody-dependent cellular cytotoxicity).
      • Examples:
        • Autoimmune-hemolytic anemia
        • Immune thrombocytopenia
        • Transfusion reactions, hyperacute rejection
        • Hemolytic disease of the newborn
    • Inflammation—binding of antibodies to cell surfaces → activation of complement system and Fc receptor-mediated inflammation.
      • Examples:
        • Goodpasture syndrome
        • Rheumatic fever
        • Hyperacute transplant rejection
    • Cellular dysfunction—antibodies bind to cell surface receptors → abnormal blockade or activation of downstream process.
      • Examples:
        • Myasthenia gravis
        • Graves disease
        • Pemphigus vulgaris
    • Coombs test:
      • Direct Coombs test—detects antibodies attached directly to the RBC surface.
      • Indirect Coombs test—detects presence of unbound antibodies in the serum
  • Type III hypersensitivity
    • Immune complex—antigen-antibody (mostly IgG) complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes.
    • Can be associated with vasculitis and systemic manifestations.
    • In type III reaction, imagine an immune complex as 3 things stuck together: antigen-antibody-complement.
    • Examples:
      • SLE
      • Polyarteritis nodosa
      • Poststreptococcal glomerulonephritis
      • Henoch-Schonlein purpura
      • Stevens-Johnson syndrome
      • Serum sickness—the prototype immune complex disease. Antibodies to foreign proteins are produced and 1–2 weeks later, antibody-antigen complexes form and deposit in tissues → complement activation → inflammation and tissue damage.
        • Fever, urticaria, arthralgia, proteinuria, lymphadenopathy occur 1–2 weeks after antigen exposure. Serum sickness-like reactions are associated with some drugs which may act as haptens (eg, penicillin & other beta lactams, sulfonamides) and infections (eg, hepatitis B).
    • Arthus reaction—a local subacute immune complex-mediated hypersensitivity reaction. Intradermal injection of antigen into a presensitized (has circulating IgG) individual leads to immune complex formation in the skin. Characterized by edema, necrosis, and activation of complement.
  • Type IV hypersensitivity
    • Two mechanisms, each involving T cells:
      1. Direct cell cytotoxicity: CD8+ cytotoxic T cells kill targeted cells.
      2. Inflammatory reaction: effector CD4+ T cells recognize antigen and release inflammation-inducing cytokines (shown in illustration).
    • Response does not involve antibodies (vs types I, II, and III).
    • Examples: contact dermatitis (eg, poison ivy, nickel allergy), Guillain-Barré syndrome, multiple sclerosis and graft-versus-host disease.
    • Tests (purpose): PPD (tuberculosis infection); patch test (cause of contact dermatitis); Candida extract (T cell immune function).
    • 4T’s: T cells, Transplant rejections, TB skin tests, Touching (contact dermatitis).
    • Fourth (type) and last (delayed).

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