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INTRODUCTION

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A precipitous increase in incidence and prevalence of allergic diseases in the last 50 years has led to the current pandemic proportions. In some subpopulations, as many as 1 in 4 children suffers from asthma, and up to 1 in 12 has a food allergy. One explanation for this dramatic increase in allergic diseases is the “hygiene hypothesis,” which posits that a decrease in the exposure to microbes due to improved hygiene, smaller families, less breastfeeding, more immunizations, and lack of serious childhood infections results in altered immunoregulation and deviation toward an allergic disease-promoting T-helper cell 2 (TH2) response. Microbial exposure promotes the production of regulatory T cells involved in maintaining tolerance to allergens. Lack of sufficient microbial exposure may result in weakened tolerance and, in the setting of other factors such as genetic predisposition and environmental exposures, result in the promotion of allergic diseases. The important environmental exposures that can directly decrease microbial diversity, causing increased expression of atopy, include urbanization, industrialization, climate change and rising temperatures with prolonged pollen seasons, increased viability of mold, and increased aeroallergen exposure. The increased prevalence of allergic disease is directly related to these factors.

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Allergic diseases are immunologic diseases in that their genesis and manifestations result from the functioning of several components of the immune system. Disease pathogenesis is mediated by both innate immune responses, involving mast cells, basophils, eosinophils, and dendritic cells, and acquired immune responses involving T, natural killer (NK) T, and B lymphocytes. Orchestrating the allergic response is the TH2 CD4+ T-helper-cell lineage, which is now appreciated to play a central role in the pathogenesis of allergic diseases. TH2 cells recruit other components of the innate and acquired immune response by virtue of their production of a set of proatopic cytokines, including interleukin (IL)-4, IL-5, and IL-13. They promote the production of immunoglobulin (Ig) E, a key trigger of immediate hypersensitivity reactions, and help sustain chronic allergic inflammation in such diseases as asthma and eczema. Increased knowledge of allergic diseases and their pathogenesis has stimulated the development of new therapeutic approaches, including desensitization therapy with defined allergen preparations or pharmacologic interventions aimed at depleting IgE or targeting the action of mediators such as leukotrienes.

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IMMUNOLOGIC BASIS OF ATOPY

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Allergic disorders develop when individuals with a genetic predisposition are exposed to environmental triggers. A unifying attribute of these disorders is atopy, defined as a genetically determined predisposition (and, hence, tending to be familial) to generate IgE antibodies on exposure to environmental antigens. Subsequent exposure to the offending antigen, or allergen, triggers an immediate hypersensitivity reaction. IT is an IgE-mediated tissue response that is characterized by increased vascular permeability, vasodilatation, smooth muscle contraction, and local cellular inflammation. The atopic (or allergic) trait integrates pathways of the acquired immune response, including specialized T-helper cells, NKT cells, and IgE-producing B cells, as well as components of the innate immune response, including mast cells, eosinophils, ...

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