Self-defense: the fruit fly style.

Abstract

The immune system of higher vertebrates consists of innate and adaptive components that differ mainly by the mechanisms of pathogen recognition: the innate immune system uses germ-line encoded receptors to recognize conserved molecular constituents of infectious microorganisms, whereas adaptive immunity is mediated by highly specific antigen receptors that are generated by gene-rearrangement processes during the ontogeny of each individual organism and are distributed clonally on the two types of lymphocytes—T cells and B cells (1, 2). As antigen receptors are generated by random processes, they can potentially be specific for any antigen. One of the essential functions of the innate immune system is believed to be instructing lymphocytes about the nature of the antigen for which they happen to be specific. This choice of effector function is essential for the effective operation of the adaptive immune response, as lymphocytes generate their antigen receptors randomly, and thus can be specific for many different types of antigen. The innate immune system sorts out whether the antigen is derived from a pathogen, in which case a response is induced and used for host defense. In cases in which the antigen is produced by the host organism, an immune response would be harmful to the host and therefore is not induced. Because the receptors of innate immunity recognize molecular structures produced only by microbes and not by the host organism, they activate signaling pathways that inform the lymphocytes of the microbial origin of the antigen. When this activation happens, lymphocytes specific for the antigen in question start to proliferate and differentiate into one of the several possible types of lymphoid effector cells. This differentiation process, however, is not pre-programmed in lymphocytes. Rather, it also depends on signals generated by the innate immune system (3–5). The best known signals of this kind are represented by a subgroup of cytokines that are believed to convey information concerning the type of pathogen invading the host organism. These cytokines thus direct differentiation of the lymphocytes into effector cells, that, in turn, activate the appropriate destructive mechanism to ultimately eliminate or neutralize the microbial pathogens (6). Additionally, some of the lymphocytes derived from the same clone differentiate into long-lived cells that retain the imprint of the instructions they received on initial infection. These cells can rapidly produce the same effector responses to all subsequent infections with the same pathogen. This sophisticated mechanism provides for long-lasting immunological memory to pathogens encountered during the lifetime of the host organism.