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).