Chemical-specific properties co-determine the type of adverse immune response

Many drugs but also environmental pollutants may cause adverse reactions in susceptible individuals that are reminiscent of autoimmune syndromes. Apart from a number of predisposing often inherent, idiosyncratic determinants, chemical-specific properties might be involved as well. Notably, reactive chemicals or metabolites may provoke formation or release of immunosensitizing neo-antigens (a.o. hapten-carrier complexes or cryptic epitopes). In addition reactive chemicals but also certain inert chemicals may trigger macrophages and other inflammatory cells to release proinflammatory products that, via elicitation of costimulatory help, support hapten- or neo-antigen-specific T cell activation. In addition, chemicals may influence immunoregulatory processes and modulate for instance the balance between type 1 and type 2 responses. Here, we review data showing that chemically induced upregulation of second or costimulatory signals co-determines not only whether, but also what type of an adverse immune response (type 1 or type 2) is triggered.