The Gell-Coombs Classification of Hypersensitivity Reactions

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The original Gell and Coomb’s classification categorizes hypersensitivity reactions into four subtypes according to the type of immune response and the effector mechanism responsible for cell and tissue injury: type I, immediate or IgE mediated; type II, cytotoxic or IgG/IgM mediated; type III, IgG/IgM immune complex mediated; and type IV, delayed-type hypersensitivity or T-cell mediated.

The classification has been improved so that type IIa is the former type II and type IIb is antibody-mediated cell stimulating (Graves Disease and the “autoimmune” type of chronic idiopathic urticaria). Type IV has four major categories: type IVa is CD4(+)Th1 lymphocyte mediated with activation of macrophages (granuloma formation and type I diabetes mellitus); type IVb is CD4(+)Th2 lymphocyte mediated with eosinophilic involvement (persistent asthma and allergic rhinitis); type IVc is cytotoxic CD8(+) T lymphocyte with involvement of perforin-granzyme B in apoptosis (Stevens-Johnson syndrome and toxic epidermal necrolysis); type IVd is T-lymphocyte-driven neutrophilic inflammation (pustular psoriasis and acute generalized exanthematous pustulosis). Some diseases have multiple types of immunologic hypersensitivity.


Classification of hypersensitivity reactions

Classification Immunoreactants Clinical Presentation
Type I Mast cell mediated, IgE dependent (anaphylactic, and IgE independent) Anaphylaxis, urticaria, angioedema, asthma, and allergic rhinitis
Type IIa Antibody-mediated cytotoxic reactions (IgG and IgM antibodies complement often involved) Immune cytopenias
Type IIb Antibody-mediated cell-stimulating reactions Graves disease and chronic idiopathic urticaria
Type III Immune complex–mediated reactions complement involved Serum sickness and vasculitis
Type IVa Th1 cell-mediated reactions macrophage activation Type 1 diabetes and contact dermatitis (with IVc)
Type IVb Th2 cell–mediated reactions eosinophilic inflammation Persistent asthma and allergic rhinitis
Type IVc Cytotoxic T cell-mediated
(perforin/granzyme B involved)
Stevens-Johnson syndrome and toxic epidermal keratinocytes (TEN)
Type IVd T-cell-mediated neutrophilic inflammation Acute generalized exanthematous pustulosis (AGEP) and Behcet disease



  1. Dispenza MC. Classification of hypersensitivity reactions. Allergy Asthma Proc. 2019;40(6):470-473. [Medline]
  2. Uzzaman A, Cho SH. Chapter 28: Classification of hypersensitivity reactions. Allergy Asthma Proc. 2012;33 Suppl 1:96-99. [Medline]
  3. Rajan TV. The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation. Trends Immunol. 2003;24(7):376-379. [Medline]

Created Jun 16, 2020.