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 |
References:
- Dispenza MC. Classification of hypersensitivity reactions. Allergy Asthma Proc. 2019;40(6):470-473. [Medline]
- Uzzaman A, Cho SH. Chapter 28: Classification of hypersensitivity reactions. Allergy Asthma Proc. 2012;33 Suppl 1:96-99. [Medline]
- Rajan TV. The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation. Trends Immunol. 2003;24(7):376-379. [Medline]
Created Jun 16, 2020.
