Allergy is an exaggerated, hypersensitive immune response to innocuous environmental antigens, characterised by inflammation and mediated by immunoglobulin E (IgE) antibodies. Symptoms of allergy depend on the site of allergen contact and range from being uncomfortable (itching, sneezing and breathlessness) to serious (anaphylaxis). The development of allergy is due to environmental and genetic factors; the heritable component is known as atopy, defined as a predisposition to the overproduction of IgE. The prevalence of allergies such as hay fever (seasonal allergic rhinitis), eczema (atopic dermatitis) and asthma are increasing in Westernised societies. Antihistamines are the first‐line drug treatment for allergy; however, these often fail to alleviate all symptoms satisfactorily and are not clinically effective in asthma, illustrating the heterogeneity of allergic disorders. This has necessitated the development of alternative medication for asthma, which targets airway symptoms, for example, β2‐adrenergic receptor agonists. New, more effective therapeutic approaches are still required to treat allergic disease.

Key Concepts:

  • Allergy describes a variety of symptoms, which cause discomfort but can be life threatening.

  • Allergic symptoms are a defining feature of diseases such as hay fever, eczema, asthma and food allergy.

  • Atopy is a heritable trait (defined by elevated IgE or positive skin prick test), which predisposes an individual to allergic disease.

  • Allergies are becoming increasingly common in Westernised societies and represent a significant economic burden, but the reasons for this are not fully understood.

  • Recent improvements in technology have facilitated studies, which link genetic variants to atopy susceptibility, with confidence.

  • New therapeutics are needed to more adequately treat symptoms of allergic diseases such as hay fever, eczema and asthma.

  • Histamine is a key inflammatory mediator, the action of which might be targeted in new ways to treat the symptoms of allergic disease.

Keywords: allergy; atopy; IgE; asthma; hay fever; eczema; food allergy; histamine

Figure 1.

Allergic sensitisation in the airways. Processing of an allergen at the airway epithelium by dendritic cells induces their migration into lymphatic regions for antigen presentation to naïve T cells (Th0). Migration is also stimulated by TSLP, a cytokine produced from epithelial cells on allergen contact. IL‐4 induces differentiation of Th0 to Th2 cells, which activate B cells via costimulation of cell surface receptors, in the presence of IL‐4 and IL‐13 from Th2, Th0 and mast cells. Allergen‐specific IgE antibodies produced by stimulated B cells prime tissue‐resident mast cells for activation on subsequent allergen exposure by binding to FcεRI receptors. TSLP, thymic stromal lymphopoietin; MHC, .

Figure 2.

Early phase of the allergic response in the airways. Allergen binding to specific IgE bound to FcεRI receptors on mast cells (and basophils) causes cross‐linking and degranulation, releasing preformed inflammatory mediators that affect various cell and tissue types, resulting in allergic symptoms shown in red. On allergen contact, the epithelium releases IL‐33, which also stimulates the release of IL‐4 from activated basophils. The recruitment of circulating leucocytes including eosinophils and neutrophils, as well as further Th2 cells, mast cells and basophils, is initiated by cytokines and chemokines such as IL‐4 and RANTES. TNF‐α, tumour necrosis factor‐α; PGD2, prostaglandin D2; LTB4, leukotriene B4; MCP‐1, monocyte chemotactic protein‐1; LTD4, leukotriene D4; Cys‐LTs, cysteinyl leukotrienes; PAF, platelet‐activating factor; VEGF‐A, vascular endothelial growth factor A; ICAM‐1, intercellular adhesion molecule‐1; VCAM‐1, vascular cell adhesion molecule‐1; RANTES, regulated on activation, normal T cell expressed and secreted.

Figure 3.

Late phase of the allergic response in the airways. Newly synthesised inflammatory mediators recruit circulating leucocytes to the site of allergen contact several hours following the early phase response. Mediators including IL‐4, IL‐13, IL‐8 and GM‐CSF, released from infiltrating leucocytes and structural cells, maintain activation, proliferation and recruitment of inflammatory cells. Other products, such as eosinophil major basic protein, cause damage to structural cells in the vicinity. Symptoms of the early phase response recur. MBP, major basic protein; RANTES, regulated on activation, normal T cell expressed and secreted; GM‐CSF, granulocyte‐macrophage colony‐stimulating factor; PGD2, prostaglandin D2; LTD4, leukotriene D4; TNF‐α, tumour necrosis factor‐α; Cys‐LTs, cysteinyl leukotrienes.

Figure 4.

Asthmatic airway pathology. This schematic comparison of a normal airway with that observed in severe chronic asthma indicates histological changes that accompany recurring inflammation seen in asthma over time. Unlike that of the unaffected individual, the bronchial mucosa from the severe asthmatic displays thickening of the basement membrane, airway smooth muscle hypertrophy, leucocyte infiltration, epithelial cell desquamation, goblet cell hyperplasia in the epithelial lining accompanied by mucus hypersecretion and plugging of the bronchial lumen, as well as oedema and collagen deposition in the submucosal area. Not drawn to scale.

Figure 5.

Factors leading to the development of allergy. Both environmental and genetic influences determine the development of sensitisation and a Th2‐dominant environment, which eventually leads to allergic phenotypes.



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Hodge, Emily, and Sayers, Ian(Feb 2013) Allergy. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001887.pub3]