Clinical allergic diseases are predominately type I, or IgE mediated. Approximately 40 percent of people in Western nations are inclined toward an exaggerated IgE response to multiple environmental aller-gens such as pollen or animal dander. This allergic state, known as atopy, is the result of multiple genetic and environmental factors.
Our current understanding of the devel-opment of an IgE response favors a TH2 T-cell induction. When specific inhaled, ingested, or absorbed proteins, or aller-gens, appropriately stimulate this subset of the T-cell population, a series of cellular reactions occurs that leads to IgE antibody production.
Inhalation of most proteins does not cause IgE-mediated responses, whereas a limited number of small protein aller-gens can elicit such reactions. Although the mechanism of allergic induction is not completely clear, some general prin-ciples have emerged. Allergens presented transmucosally at very low doses induce IgE responses by TH2 cells. This subset of cells produces the primary cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13). These interleukins interact with receptors on B lymphocyte cell surfaces, which promote class switching to the IgE antibody subclass. The subsequent class switch produces antigen-specific IgE anti-bodies with specificity toward common allergens such as pollen, animal dander, food, or venom.
Genetic studies of atopic families have identified regions on chromosome 11q and 5q that affect IgE production. Chromosome 5 contains multiple genes, including those for IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor. Eosinophil sur-vival and mast cell proliferation are just a few pro-allergic effects of these cytokines. Chromosome 11 encodes the beta subunit of the high-affinity IgE receptor. Increased expression of this receptor on mast cells leads to a more vehement response to small numbers of antigens. This increased expression explains how exposure to min-ute amounts of allergen, such as venom from a stinging insect, can produce sys-temic anaphylaxis.
Although atopy has a strong genetic component, environmental factors best explain the recent global trend toward increased prevalence of allergic disease. Predictive factors include the following:
(1) decreased exposure to infectious dis-ease during early childhood, (2) changes in diet, (3) higher levels of allergen expo-sure, and (4) increased environmental pollution. Of these factors, variances in exposure to infectious disease appear to have the greatest correlation with atopy. Epidemiological studies point out a nega-tive association between atopic disease in children and a history of measles or hepa-titis A virus infection. It is hypothesized that infections such as these tilt the pro-duction of cytokines toward interferon gamma (IFN-γ) and the TH1 cytokines, thereby decreasing production of TH2 allergic cytokines such as IL-4. This the-ory’s attractiveness may be its ability to explain the global increase in atopy due to decreased infection rates in Western-ized regions with aggressive vaccination programs. Current research trials use this theory with protein vaccines that promote TH1 responses to shift the immune sys-tem away from this allergic phenotype. We highlight the common clinical manifestations of atopy and dem-onstrate how immunological reactivity to key antigens underscores each condition. Although the Gell and Coombs classifica-tion is not universally applicable, the fun-damental immunological processes apply in most of the common clinical hypersen-sitivity states discussed next.