Hypersensitivity reactions

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Gell and Coombs Classification of Hypersensitivity

Hypersensitivity reactions are exaggerated or inappropriate immune responses to antigens, causing tissue damage rather than protection. These are categorized into four distinct types (Type I-IV) based on the immunological mechanism involved.

The Four Types: Quick Reference (ACID)

Type Mechanism Key Mediators Clinical Examples
I Anaphylactic/Atopic IgE, Mast cells, Basophils Anaphylaxis, Asthma, Hay fever
II Cytotoxic (Antibody-mediated) IgG, IgM, Complement Autoimmune hemolytic anemia, Goodpasture
III Immune Complex Ag-Ab complexes, Complement SLE, Serum sickness, Polyarteritis nodosa
IV Delayed-type T-cells, Macrophages Contact dermatitis, TB skin test, Transplant rejection

Detailed Mechanisms

Type I: Immediate Hypersensitivity

Occurs within minutes of antigen exposure in a sensitized individual. Initial exposure induces class switching of B cells to IgE production. IgE binds to Fc receptors on mast cells and basophils. Subsequent exposure leads to cross-linking of IgE, causing degranulation and release of histamine, tryptase, and leukotrienes.

Type II: Antibody-Mediated Hypersensitivity

Antibodies (IgG or IgM) bind to antigens on cell surfaces or extracellular matrix. Damage occurs via three pathways:

  • Opsonization/Phagocytosis: Antibody/complement-coated cells are cleared by macrophages.
  • Complement-mediated lysis: Formation of the Membrane Attack Complex (MAC).
  • Antibody-Dependent Cellular Cytotoxicity (ADCC): Natural Killer cells bind Fc receptors and induce apoptosis.

Type III: Immune Complex-Mediated Hypersensitivity

Antigen-antibody complexes are formed in circulation and subsequently deposited in tissues (vessels, joints, glomeruli). The deposition triggers complement activation, which attracts neutrophils. Neutrophils release lysosomal enzymes and reactive oxygen species, causing local tissue damage (vasculitis).

Type IV: Delayed-Type Hypersensitivity

The only type not mediated by antibodies. Driven by sensitized T cells (CD4+ or CD8+). Upon re-exposure, Th1 cells release cytokines (like IFN-gamma) that activate macrophages, leading to inflammation and tissue injury. Because it requires recruitment and activation of T cells, the reaction is delayed (typically 24–48 hours).