As described in Chapter 4, the existence of a human serum factor that reacts with allergens was first demonstrated by K. Prausnitz and H. Kustner in 1921. The local wheal and flare response that occurs when an allergen is injected into a sensitized individual is called the P-K reaction. Because the serum components responsible for the P-K reaction displayed specificity for allergen, they were assumed to be antibodies, but the nature of these P-K antibodies, or reagins, was not demonstrated for many years.
Experiments conducted by K. and T. Ishizaka in the mid-1960s showed that the biological activity of reaginic antibody in a P-K test could be neutralized by rabbit antiserum against whole atopic human sera but not by rabbit antiserum specific for the four human immunoglobulin classes known at that time (IgA, IgG, IgM, and IgD) (Table 16-2). In addition, when rabbits were immunized with sera from ragweed-sensitive individuals, the rabbit antiserum could inhibit (neutralize) a positive ragweed P-K test even after precipitation of the rabbit antibodies specific for the human IgG, IgA, IgM, and IgD isotypes. The Ishizakas called this new isotype IgE in reference to the E antigen of ragweed that they used to characterize it.
Serum IgE levels in normal individuals fall within the range of 0.1-0.4 ^g/ml; even the most severely allergic individuals rarely have IgE levels greater than 1 ^g/ml. These low levels made physiochemical studies of IgE difficult; it was not until the discovery of an IgE myeloma by S. G. O. Johansson and H. Bennich in 1967 that extensive chemical analysis of IgE could be undertaken. IgE was found to be composed of two heavy € and two light chains with a combined molecular weight of 190,000. The higher molecular weight as compared with IgG (150,000) is due to the presence of an additional constant-region domain (see Figure 4-13). This additional domain (CH4) contributes to an altered conformation of the Fc portion of the molecule that enables it to bind to glyco-protein receptors on the surface of basophils and mast cells. Although the half-life of IgE in the serum is only 2-3 days, once IgE has been bound to its receptor on mast cells and basophils, it is stable in that state for a number of weeks.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.