MOLECULAR MECHANISMS OF TOXICANT-INDUCED IMMUNOSUPPRESSION - ROLE OF 2ND MESSENGERS

Changes in immunocompetence following chemical exposure have been esta blished for a wide variety of unrelated agents. For the vast majority of immunotoxic compounds thus far identified, disruption of normal imm une function is clearly mediated through direct interactions between t he agent, or its metabolite, and immunocompetent cells. Regardless of whether this interaction occurs at the level of the cell membrane or a t intracellular sites, basic regulatory processes mediated by second m essengers are often altered. These alterations can ultimately result i n immunologic dysfunction, which is most often manifested as immunosup pression. The specific disruptions in intracellular signaling produced by a number of immunotoxic compounds have now been identified, leadin g to a basic understanding of their molecular mechanism of action. Equ ally important, through the application of these agents as biological probes, new insights have been gained pertaining to which intracellula r processes control which cellular functions within various population s of immunocompetent cells.