Question

While, fortunately, rare, with an estimated frequency of 5 or less occurrences per 10,000 cases of penicillin treatment, anaphylactic shock resulting in nausea, vomiting, pruitus (itching), urticaria(hives), wheezing, laryngeal edema and, ultimately, cardiac collapse---and, possible death---can occur in minutes after the administration of the antibiotic to a "sensitized" patient . The cause of this clinical manifestation, when it occurs, is due to an unbeknown Immediate Hypersensitivity allergy existing in the patient to the drug due to the patient's prior exposure to penicillin. This prior or sensitizing exposure can result in the generation of high levels of Gamma E-antibody-sensitized-Mast-cells which immediately degranulate releasing vasoactive amines etc. upon the patient's receipt of a "shocking dose" of the drug (in this case, allergen)! However, for this Unit on "antigens" the question to be entertained is this: "Since Penicillin G is is a small molecular weight molecule (<400 MW), how does anti-Pen-Gamma E-antibody (Anti-Penicilloyl-IgE) get generated against it?"

Answer 1

Penicillin is a low molecular weight molecule and a hapten as it can elicit an allergic immune response. Haptens cannot on their own induce antibody formation. It needs to be covalent linked to a carrier molecule to induce antibody production. Penicillin induces an immune response in the patients due to its breakdown products that can form hapten-carrier complexes when it binds to tissue and plasma proteins.

The unstable b -lactam ring in the degraded penicillin interact with lysine residues (amino groups) in the tissue and plasma proteins. This binding forms a penicilloyl epitope known as benzylpenicilloyl (BPO). BPO is the "major determinant" and is immuno-dominant in the immune response. There are 3 epitopes in BPO molecule: the side chain, the whole molecule bound to a carrier by ring opening, and the bicyclic nuclear structure.

Minor determinant are the molecular rearrangements of carboxyl and thiol groups with b -lactam. Both determinants differ in the amount of hapten available for binding to mast cells. The complexes of breakdown products of penicillin and the native proteins are exposed to mast cells and basophils in affected individuals. Anti-Pen-Gamma E-antibodies (Anti-Penicilloyl-IgE) are formed when there is significant amount of drug epitopes are formed.