Unifying Concepts

The Gell-Coombs Classification of Hypersensitivity Reactions

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.

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