Hypersensitivity: IgE‐Mediated (Type I)

Abstract

Hypersensitivity reactions, which are classified into 4 types (type I‐IV), are over‐zealous immune responses due to the fact that they are directed against harmless antigens, are of excessive magnitude, and/or are occurring in inappropriate body locations. Type I, or sometimes type IV, hypersensitivity reactions are responsible for the symptoms of allergy. Huge numbers of people suffer from allergic responses, which can vary in significance from being mildly inconvenient to resulting in rapid death. Allergic responses due to type I hypersensitivity are often referred to as atopic allergy and are mediated by the IgE class of antibody bound to tissue mast cells and to circulating blood basophils. Cross‐linking of the IgE by allergen results in the release of a plethora of inflammatory mediators that cause the symptoms. A variety of tests are available to assist in the diagnosis of type I hypersensitivity, and a range of therapies are used to control the diseases it causes.

Key Concepts

  • There are four main types of hypersensitivity reactions, which are characterised by inappropriate or exaggerated immune responses.
  • Type I hypersensitivity reactions involve the activation of tissue mast cells and blood basophils when IgE molecules bound to their surface become linked together by an allergen.
  • Substantial numbers of individuals develop allergies due to type I (IgE‐mediated) hypersensitivity, also referred to as atopic allergy.
  • Allergies that are caused by type I hypersensitivity include hay fever, asthma, eczema and food allergy.
  • The IgE antibodies are bound to the cell surface of the mast cells and basophils via a high affinity Fc receptor for IgE (FcϵR1).
  • Susceptibility to the development of type I hypersensitivity has been linked to polymorphisms in several different genes.
  • Activation of mast cells and basophils leads to the release of many different mediators of inflammation including histamine, prostaglandins and leukotrienes.
  • The release of inflammatory mediators by mast cells and basophils is a component of normal immune responses, but in atopic allergy the response is inappropriate because it is against a substance that would not normally pose a threat.
  • There are a number of different approaches to the treatment of atopic allergy, but the best strategy in individuals that have already become sensitised, and when feasible, is avoidance of re‐exposure to the allergen.

Keywords: allergen; allergy; basophil; histamine; inflammation; mast cell

Figure 1. The activation of mast cells and basophils by IgE. Mast cells in mucosal and connective tissues, and basophils in the blood circulation, become ‘sensitised’ with IgE when their high affinity receptors (FcϵR1) for this class of antibody bind to the Fc portion of the IgE. This does not trigger the cell. However, if the IgE is specific for an antigen (e.g. associated with a nematode worm or an allergen) that is subsequently encountered, then the antigen can link together (‘cross‐link’) the antibody that therefore results in cross‐linking of the FcϵR1 and subsequent activation of the mast cell/basophil, resulting in degranulation and the synthesis of mediators of inflammation.
Figure 2. Immune systems genes implicated in type I hypersensitivity. Multiple genes have been implicated that act at various stages in the type I hypersensitivity response. Examples include those indicted by red boxes. IL‐2Rβ, interleukin‐2 receptor β chain; PAMP, pathogen‐associated molecular pattern; PRR, pattern recognition receptor; TSLP, thymic stromal lymphopoietin; TSLPR, TSLP receptor. Reproduced with permission from Roitt's Essential Immunology 13th edition. Peter J Delves, Seamus J Martin, Dennis R Burton, and Ivan M Roitt 2017 © John Wiley & Sons Ltd.
Figure 3. Diagnosis and treatment of atopic allergy.
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Delves, Peter J(May 2017) Hypersensitivity: IgE‐Mediated (Type I). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000965.pub3]