Allergic reactions occur when an individual who has produced IgE antibody in response to an innocuous antigen, or allergen, subsequently encounters the same allergen. The allergen triggers the activation of IgE-binding mast cells in the exposed tissue, leading to a series of responses that are characteristic of allergy. As we learned in Chapter 9, there are circumstances in which IgE is involved in protective immunity, especially in response to parasitic worms, which are prevalent in less developed countries. In the industrialized countries, however, IgE responses to innocuous antigens predominate and allergy is an important cause of disease. Almost half the populations of North America and Europe have allergies to one or more common environmental antigens and, although rarely life-threatening, these cause much distress and lost time from school and work. Because of the medical importance of allergy in industrialized societies, much more is known about the pathophysiology of IgE-mediated responses than about the normal physiological role of IgE.
The term allergy was originally defined by Clemens Von Pirquet as “an altered capacity of the body to react to a foreign substance,” which was an extremely broad definition that included all immunological reactions. Allergy is now defined in a much more restricted manner as “disease following a response by the immune system to an otherwise innocuous antigen.” Allergy is one of a class of immune system responses that are termed hypersensitivity reactions. These are harmful immune responses that produce tissue injury and may cause serious disease. Hypersensitivity reactions were classified into four types by Coombs and Gell. Allergy is often equated with type I hypersensitivity (immediate-type hypersensitivity reactions mediated by IgE), and will be used in this sense here.
There are four types of hypersensitivity reaction mediated by immunological mechanisms that cause tissue damage
Types I–III are antibody-mediated and are distinguished by the different types of antigens recognized and the different classes of antibody involved. Type I responses are mediated by IgE, which induces mast-cell activation, whereas types II and III are mediated by IgG, which can engage Fc-receptor and complement-mediated effector mechanisms to varying degrees, depending on the subclass of IgG and the nature of the antigen involved. Type II responses are directed against cell-surface or matrix antigens, whereas type III responses are directed against soluble antigens, and the tissue damage involved is caused by responses triggered by immune complexes. Type IV hypersensitivity reactions are T cell-mediated and can be subdivided into three groups. In the first group, tissue damage is caused by the activation of macro-phages by TH1 cells, which results in an inflammatory response. In the second, damage is caused by the activation by TH2 cells of inflammatory responses in which eosinophils predominate; in the third, damage is caused directly by cytotoxic T cells (CTL).