Figure 3: Induction of IgE by hapten-protein adducts, elicitation of MC degranulation by fake antigen
Induction of IgE- and MC-unresponsiveness by hapten-protein adducts and of MC degranulation by fake antigen.
① Covalently bound hapten-carrier adducts (=true antigen, ) are taken up by APC like DC, processed and presented as drug-peptide on HLA to T cells. Some specific T cells react and secrete cytokines like IL-4, IL-13 ②, which booster B cell maturation to plasma cells secreting hapten-carrier specific IgE. These IgE bind to high-affinity FcεRI on mast cells (MC), where they are cross-linked by hapten-carrier complexes. The increasing amount of immune complexes (hapten-carrier/IgE antibodies/FcεRI) make MC unresponsive ③ to the specific antigen. The sensitization phase remains asymptomatic, although antigen (continued use of drug), IgE and mast cells are present.
After a drug free interval the patient may be re-challenged by the drug ④: Some drugs are able to form non-covalent drug-carrier complexes [ ] rapidly and in high amount (“fake antigens”); they look similar/identical to true antigen and can bind to the preformed drug specific IgE on MC: the quasi immediately and ubiquitously available, large amount of fake antigens can overcome MC-unresponsiveness and elicit a generalized MC-degranulation with anaphylaxis.