Hypersensitivity: IgE‐Mediated (Type I)


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 de novo 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.


Abraham SN and St John AL (2010) Mast cell‐orchestrated immunity to pathogens. Nature Reviews in Immunology 10 (6): 440–452.

Akdis CA and Akdis M (2015) Advances in allergen immunotherapy: aiming for complete tolerance to allergens. Science Translational Medicine 7 (280): 280ps6.

Astudillo AM , Balgoma D , Balboa MA and Balsinde J (2012) Dynamics of arachidonic acid mobilization by inflammatory cells. Biochimica et Biophysica Acta 1821 (2): 249–256.

Blank U , Charles N and Benhamou M (2016) The high‐affinity immunoglobulin E receptor as pharmacological target. European Journal of Pharmacology 5 (778): 24–32.

Caballero ML and Quirce S (2015) Identification and practical management of latex allergy in occupational settings. Expert Reviews in Clinical Immunology 11 (9): 977–992.

Cabanillas B and Novak N (2016) Atopic dermatitis and filaggrin. Current Opinion in Immunology 42: 1–8.

Canonica GW , Baena‐Cagnani CE , Compalati E , et al. (2013) 100 years of immunotherapy: the Monaco Charter. International Archives of Allergy and Immunology 160 (4): 346–349.

Du Toit G , Roberts G , Sayre PH , et al. (2015) Randomized trial of peanut consumption in infants at risk for peanut allergy. New England Journal of Medicine 372 (9): 803–813.

Durham SR and Penagos M (2016) Sublingual or subcutaneous immunotherapy for allergic rhinitis? Journal of Allergy and Clinical Immunology 137 (2): 339–349.

Engebretsen KA and Thyssen JP (2016) Skin barrier function and allergens. Current Problems in Dermatology 49: 90–102.

Fromer L (2016) Prevention of anaphylaxis: the role of the epinephrine auto‐injector. American Journal of Medicine 129 (12): 1244–1250.

Fujimura KE , Sitarik AR , Havstad S , et al. (2016) Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nature Medicine 22 (10): 1187–1191.

Furue M , Chiba T , Tsuji G , et al. (2017) Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Allergology International pii: S1323‐8930(16)30171.

Gaudenzio N , Sibilano R , Marichal T , et al. (2016) Different activation signals induce distinct mast cell degranulation strategies. The Journal of Clinical Investigation 126 (10): 3981–3998.

Grencis RK (2015) Immunity to helminths: resistance, regulation, and susceptibility to gastrointestinal nematodes. Annual Review of Immunology 33: 201–225.

Hernandez L , Papalia S and Pujalte GG (2016) Anaphylaxis. Primary Care 43 (3): 477–485.

Holgate ST and Polosa R (2008a) Treatment strategies for allergy and asthma. Nature Reviews Immunology 8 (3): 218–230.

Jafilan L and James C (2015) Urticaria and allergy‐mediated conditions. Primary Care 42 (4): 473–483.

Jalbert I and Golebiowski B (2015) Environmental aeroallergens and allergic rhino‐conjunctivitis. Current Opinion in Allergy and Clinical Immunology 15 (5): 476–481.

James C and Bernstein JA (2017) Current and future therapies for the treatment of histamine‐induced angioedema. Expert Opinion in Pharmacotherapy 25: 1–10.

Kakli HA and Riley TD (2016) Allergic rhinitis. Primary Care 43 (3): 465–475.

Kim JS and Sampson HA (2012) Food allergy: a glimpse into the inner workings of gut immunology. Current Opinion in Gastroenterology 28 (2): 99–103.

Koczulla AR , Vogelmeier CF , Garn H and Renz H (2016) New concepts in asthma: clinical phenotypes and pathophysiological mechanisms. Drug Discovery Today pii: S1359‐6446(16)30425‐1.

Kostner L , Anzengruber F , Guillod C , et al. (2017) Allergic Contact Dermatitis. Immunology and Allergy Clinics of North America 37 (1): 141–152.

Lopes Dos Santos JM (2005) How to stop the allergy march. International Journal of Immunopathology and Pharmacology 18 (4 Suppl): 39–40.

Mahmoudi M (ed) (2016) Allergy and Asthma: Practical Diagnosis and Management. Switzerland: Springer International Publishing.

Moon TC , Befus AD and Kulka M (2014) Mast cell mediators: their differential release and the secretory pathways involved. Frontiers in Immunology 14 (5): 569.

Moran TP and Burks AW (2015) Is clinical tolerance possible after allergen immunotherapy? Current Allergy and Asthma Reports 15 (5): 23.

Nguyen TH , Stokes JR and Casale TB (2011) Future forms of immunotherapy and immunomodulators in allergic disease. Immunology and Allergy Clinics of North America 31 (2): 343–365.

Ohtsuka Y (2015) Food intolerance and mucosal inflammation. Pediatrics International 57 (1): 22–29.

Poulsen LK and Hummelshoj L (2007) Triggers of IgE class switching and allergy development. Annals of Medicine 39 (6): 440–456.

Rosenberg HF , Phipps S and Foster PS (2007) Eosinophil trafficking in allergy and asthma. Journal of Allergy and Clinical Immunology 119 (6): 1303–1310.

Sandig H and Bulfone‐Paus S (2012) TLR signalling in mast cells: common and unique features. Frontiers in Immunology 3: 185.

Santiago HC and Nutman TB (2016) Human helminths and allergic disease: the hygiene hypothesis and beyond. American Journal of Tropical Medicine and Hygiene 95 (4): 746–753.

Schnyder B and Brockow K (2015) Pathogenesis of drug allergy – current concepts and recent insights. Clinical and Experimental Allergy 45 (9): 1376–1383.

Smits HH , van der Vlugt LE , von Mutius E and Hiemstra PS (2016) Childhood allergies and asthma: new insights on environmental exposures and local immunity at the lung barrier. Current Opinion in Immunology 42: 41–47.

Strachan DP (1989) Hay fever, hygiene, and household size. British Medical Journal 299 (6710): 1259–1260.

Togias A , Cooper SF , Acebal ML , et al. (2017) Addendum guidelines for the prevention of peanut allergy in the United States: summary of the National Institute of Allergy and Infectious Diseases‐sponsored expert panel. Pediatric Dermatology 34 (1): 5–12.

Valenta R , Ferreira F , Focke‐Tejkl M , et al. (2010) From allergen genes to allergy vaccines. Annual Review of Immunology 28: 211–241.

Wu LC and Scheerens H (2014) Targeting IgE production in mice and humans. Current Opinion in Immunology 31: 8–15.

Yu W , Freeland DM and Nadeau KC (2016) Food allergy: immune mechanisms, diagnosis and immunotherapy. Nature Reviews in Immunology 16 (12): 751–765.

Further Reading

American Academy of Allergy, Asthma & Immunology (2017) Allergies. https://www.aaaai.org/conditions‐and‐treatments/allergies

Anagnostou K and Clark A (2016) Oral immunotherapy for peanut allergy. Annual Review of Medicine 67: 375–385.

Delves PJ (2016) Allergic, Autoimmune, and Other Hypersensitivity Disorders. Merck Manual Professional Version. http://www.msdmanuals.com/en‐gb/professional/immunology‐allergic‐disorders

Holgate ST and Polosa R (2008b) Treatment strategies for allergy and asthma. Nature Reviews Immunology 8: 218–230.

Keet CA and Wood RA (2014) Emerging therapies for food allergy. Journal of Clinical Investigation 124 (5): 1880–1886.

Lafaille JJ and Curotto de Lafaille MA (eds) (2016) IgE antibodies: generation and function. In: Current Topics in Microbiology and Immunology. Springer.

Licona‐Limón P , Kim LK , Palm NW and Flavell RA (2013) TH2, allergy and group 2 innate lymphoid cells. Nature Immunology 14 (6): 536–542.

Longo G , Berti I , Burks AW , et al. (2013) IgE‐mediated food allergy in children. The Lancet 382 (9905): 1656–1664.

Stone KD , Prussin C and Metcalfe DD IgE (2010) Mast cells, basophils, and eosinophils. Journal of Allergy and Clinical Immunology 125 (2 Suppl 2): S73–S80.

Unsworth DJ and Lock RJ (2014) Food allergy testing. Advances in Clinical Chemistry 65: 173–198.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
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]