Lymphokine Regulation of Macrophage Effector Activities

Abstract

Host reaction to the changes in homeostatic balance induced by infection or neoplasia is characterized by a complex, but carefully orchestrated series of events called inflammation. Cells involved in this process communicate with their environment, and themselves, through multi-directional networks of inflammatory signals (cytokines) that induce, amplify, or suppress particular responses. Analysis of the cells that are involved in inflammation repeatedly points to a single cell in control: the macrophage. These cells serve not only as the initiators of antigen-specific immunity through antigen processing and presentation, but also as effector cells for elimination of the offending pathogen once Immunity has been established. Of particular interest in recent years has been the signals and sequence of events that regulate the onset of nonspecific cytotoxic effector reactions of macrophages. This interest initiated from the original studies of Mackaness, who observed that mice infected with one bacterium were able to survive normally lethal infections with completely unrelated bacteria. After years of experimental analysis, it became clear that the cellular basis for this nonspecific resistance had two obligate components: T lymphocytes and macrophages. Immune T cells respond to antigen in context of histocompatability antigens on the macrophage, and release hormone-like cytokines (lymphokines, LK), that regulate macrophage function. A subset of these LK, in turn, activates macrophages to become nonspecific killer cells. These activated cells can now eliminate not only the inciting infectious agent that induced the immune response, but also a wide variety of completely unrelated viral, bacterial, fungal, parasitic, and neoplastic targets. The activation of macrophages for nonspecific cytotoxic effector functions occurs early in the evolution of an immune response, and constitutes the host’s first opportunity for containment of the invading microorganism.