Hypersensitivity and Toxicity 141 THE IMMUNOCHEMICAL BASIS FOR PENICILLIN ALLERGY

ALTHOUGH the incidence of drug allergy in general is low, there are a few drugs which are notable exceptions. For example, Nirvanol, a drug which was once used for treatment of chorea, caused allergic symptoms in nearly every patient (Sherman, 1947). Moreover, among organic molecules which are not of therapeutic value but which are analogous to drugs structurally, many examples can be cited where there is a high sensitizing capacity (Landsteiner, 1945). These chemicals which are potent sensitizers have the common property that they are able to react with proteins to form a stable bond. The two main types of combination between drugs and proteins are shown in Fig. 1. After the adsorption of a drug to protein, the complex can be readily dissociated and both drug and protein are recovered in their original form. Nearly all drugs are bound reversibly to some degree by protein, especially the serum albumins. In forming a stable or covalent bond a portion of the drug molecule must be in a reactive form. Reaction takes place with amino acid residues which are capable of assuming a charge on their side chains, such as lysine, tyrosine and histidine. The stability of the bond formed will in many instances be comparable to that of a peptide bond. Because potent sensitizers do form stable bonds with protein in vitro, it has been postulated that immunization to a simple chemical requires the combination of that chemical with body protein; in other words, that a covalent bond is formed in vivo (Landsteiner, 1945; Eisen, 1959). In accord with this idea is the fact that a covalent conjugate, formed by reacting a protein and a chemical in vitro, is a potent antigen. By contrast, the reversible combination of a chemical with a protein does not appear to confer immunogenicity (Eisen, 1959). The application of this general concept to