Historically, hypersensitivity reactions due to immunological responses were classified by Gell and Coombs into four broad types, of which type I hypersensitivity reactions represented immediate-type allergic reactions mediated by IgE antibodies, with mast-cell activation the major final effector mechanism. Type II and III hypersensitivity responses were defined as those that were driven by antigen-specific IgG antibodies, the final effector mechanism being complement (type II) or FcR-bearing cellular effectors (type III). Finally, type IV hypersensitivity responses were depicted as being driven by cellular effectors, including lymphocytes and a variety of myeloid cell types. While the Gell and Coombs classification system provides an effective framework for understanding the mechanisms underlying some prototypic immunologic reactions, it is now becoming clear that most normal and pathologic host immune responses involve both the humoral and cellular arms of the immune system, and that the definitions provided in Chapter 11 for types 1, 2, and 3 immune response modules provide a more thorough mechanistic context for understanding disease pathogenesis, including allergic responses (see Fig. 11.5). In most allergic reactions, such as those to food, pollen, or house dust, reactions occur because the individual has become sensitized to an innocuous anti-gen—the allergen—by producing IgE antibodies against it. This is usually a result of the formation of an unwanted type 2 immune response to the allergen. Subsequent exposure to the allergen triggers the activation of IgE-binding cells, chiefly mast cells and basophils, in the exposed tissue, leading to a series of responses that are characteristic of this type of allergic reaction. In hay fever (allergic rhinoconjunctivitis), for example, symptoms occur when allergenic proteins leached out of grass or weed pollen grains come into contact with the mucous membrane of the nose and eyes. In contrast, other hypersensitivity disorders, such as allergic contact dermatitis, serum sickness, or celiac disease, are not dependent on IgE antibodies and represent unwanted immune responses driven by IgG antibodies and/or cellular immune responses.
We are all exposed regularly to common environmental agents that can cause allergic reactions in some individuals. While most of the population does not develop clinically significant allergic reactions to the majority of potential allergens, in some surveys over half of the population shows an allergic response to at least one substance in the environment. Some individuals manifest allergic responses to multiple common antigens. A predisposition to become IgE-sensitized to environmental allergens is called atopy, and later in the chapter we discuss the various factors—both genetic and environmental— that may contribute to this predisposition. Genetic factors clearly play a role in predisposing an individual to IgE-mediated allergic disease. If both parents are atopic, a child has a 40–60% chance of developing an IgE-mediated allergy, whereas the risk is much lower, on the order of 10%, if neither parent is atopic.
IgE and IgE-mediated allergic diseases.
Effector mechanisms in IgE-mediated allergic reactions.
Non-IgE-mediated allergic diseases.
Fig. 14.1 IgE-mediated reactions to extrinsic antigens. All IgE-mediated responses involve mast-cell degranulation, but the symptoms experienced by the patient can be very different depending, for example, on whether the allergen is injected directly into the bloodstream, is eaten, or comes into contact with the mucosa of the ocular or respiratory tract.