Editorial overview
Allergy and hypersensitivity: Nature versus nurture in allergy and hypersensitivity

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Introduction

Allergic diseases affect up to 20% of the population in developed countries. Ominously, the incidence of allergic diseases continues to rise. They are the most common cause of school absence, a substantial cause for absenteeism from work, and they interfere in the quality of life of adults. Allergic diseases pose an enormous burden on the economy because of their dual impact on health care cost and productivity. A better understanding of the pathogenesis of these diseases, and of the molecular mechanisms that underlie them, is essential to devise strategies to prevent their occurrence and to effectively suppress their manifestations when they take root.

The following series of articles explores the contribution of genetics and environment to allergic diseases, and suggests novel approaches to prevent and treat them.

Section snippets

The genetics of allergy and asthma

It has been known for centuries that allergic diseases have a strong genetic component. For example, clinical observations indicate that 70% of offspring from parents who are both asthmatics will suffer from asthma. Furthermore, members of a family may develop asthma, hay fever, eczema or any combination of the three, suggesting an inherited susceptibility to develop an IgE-mediated antibody response, as well as a tissue-specific predisposition to allergic inflammation. Asthma, although often

Microbes and allergy

The ‘hygiene hypothesis’ ascribes the increased prevalence and severity of allergic diseases and other diseases of immune dysregulation (e.g. Th1-mediated autoimmune diseases) in industrialized countries to decreased exposure to microbes as a result of modern public health practices [6]. This has resulted in the loss of a major source of immune provocation, with a consequent increase in pathogenic immune responses and their associated diseases. In the second article in this section, Horner and

Dendritic cells and the initiation of the allergic response

The dendritic cell (DC) is an essential player in CD4+ T-cell priming and is thought to play an important role in T-cell differentiation. DC priming of Th1 responses is well understood. The uptake of antigen in peripheral tissues by a DC in the context of a PAMP leads to DC maturation and migration to the lymph nodes (LNs) where it presents the antigen to T cells. Concomitant IL-12 production results in Th1 differentiation of T cells. Although DCs are also essential for Th2 responses, the

Regulatory T cells in allergy and asthma

The term ‘regulatory T cell’ refers to cells that actively control or suppress the function of other cells, generally in an inhibitory fashion. Four major types of CD4+ regulatory T cell have been described: Th3 cells, TR cells, CD4+CD25+ cells and NKT cells. Th3 cells are CD4+ T cells that are induced by oral antigen in the mesenteric LNs. They produce TGF-β and varying amounts of IL-4 and IL-10, and they suppress the development of autoreactive T cells that mediate experimental autoimmune

Nature and nurture in the pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease that is characterized by pruritic, eczematoid skin lesions. The prevalence of AD is steadily increasing, especially in industrialized nations, where the current lifetime prevalence in children is estimated to be 10–20%. In the fifth article of this series, Leung et al. [21] review the evidence that AD results from interactions between susceptibility genes, the host environment, skin barrier defects, bacterial and viral

Intervening with mast cell high-affinity IgE receptor signaling in the treatment of allergic diseases

The aggregation of antigen with the IgE bound to a high affinity receptor on mast cells or basophils initiates a complex series of biochemical events that result in the release of mediators that cause allergic inflammation and anaphylactic reactions. In the sixth article of this series, Siraganian [29] brings us up to date with the signaling pathways that are triggered by the high-affinity IgE receptor (FcεRI) on mast cells and basophils. He reviews recent work that shows that binding of IgE to

Conclusions

Understanding the interplay between genes and environmental factors, particularly with respect to the microbial world, promises to be the key to the complex pathogenesis of allergic diseases, and the effective prevention and treatment of these diseases. The quest will be arduous because of the number of pathways and molecules that predispose to allergy in general, and to tissue-specific allergic inflammation in particular. The role of microbial agents also promises to be complex because

Raif Geha investigates signals that trigger isotype switching to IgE, atopic dermatitis and immunodeficiency diseases.

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    Raif Geha investigates signals that trigger isotype switching to IgE, atopic dermatitis and immunodeficiency diseases.

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