IgE is prominent in the defense against extracellular parasitic organisms, especially helminths and protozoa (see Section 11-9). These parasitic organisms are prevalent in developing nations, but most serum IgE in developed nations is directed against innocuous antigens, sometimes causing allergic symptoms (Fig. 14.1). Almost half the population of North America and Europe is sensitized to one or more common environmental antigens, and, although rarely life-threatening, allergic diseases initiated by contact with a specific allergen can cause much distress and lost time from school and work. The burden of allergic diseases in the Western world is considerable, with their prevalence having more than doubled in the past 20 years. Consequently, most clinical and scientific attention paid to IgE has been directed toward its pathologic roles in allergic disease rather than its protective capacity. Until the last decade, developing countries in Africa and the Middle East reported a relatively low prevalence of allergy; however, this situation is rapidly changing, probably as a result of Western-style modernization.
In this chapter we first consider the mechanisms that favor the sensitization of an individual to an allergen, resulting in the production of antigen-specific IgE. We then describe the IgE-mediated allergic reaction itself—the pathological consequences of the interaction between allergen and the IgE bound to the high-affinity Fcε receptor on mast cells and basophils. Finally, we consider the causes and consequences of other types of immunological hypersensitivity reaction.
IgE and IgE-mediated allergic diseases.
Immediate hypersensitivity reactions are those allergic reactions caused by activation of mast cells and basophils by multivalent antigen bridging IgE bound to their cell surfaces. IgE differs from other antibody isotypes in being predominantly localized in the tissues, where it is tightly bound to the surfaces
IgE and IgE-mediated allergic diseases.
Fig. 14.2 Sensitization to an inhaled allergen. Der p 1 is a (third panel), and this IgE becomes bound to Fc receptors on common respiratory allergen that is found in fecal pellets of the resident submucosal mast cells. On a subsequent encounter with house dust mite. When an atopic individual first encounters Der p 1, Der p 1, the allergen binds to the mast cell-bound IgE, triggering subepithelial dendritic cells ingest the allergenic protein and traffic mast-cell activation and the release of mast-cell granule contents, to the draining lymph node, where TH2 cells specific for Der p 1 are which cause the symptoms of the allergic reaction (last panel). produced (first and second panels). Interaction of these T cells with Der p 1 is a protease that cleaves occludin, a protein that helps to Der p 1-specific B cells leads to the production of class-switched maintain epithelial tight junctions; the enzymatic activity of Der p 1 is plasma cells producing Der p 1-specific IgE in the mucosal tissues thought to help it pass through the epithelium.
of mast cells and some other cell types through the high-affinity IgE receptor FcεRI (see Section 10-24). Binding of antigen to IgE cross-links the high-affinity IgE receptors, causing the release of chemical mediators from the mast cells that can lead to allergic disease (Fig. 14.2). How an initial antibody response to environmental antigens comes to be dominated by IgE production in atopic individuals is still being worked out. In this part of the chapter we describe the current understanding of the factors that contribute to this process.
14-1 Sensitization involves class switching to IgE production on first contact with an allergen.