Innate Natural Killer Cell Responses to Infection

Abstract

This chapter describes and reviews the functions of natural killer (NK) cells, primarily from studies of their antitumor properties, and discusses recent advances in the understanding of NK cell responses in host defense against pathogens. The in vitro NK cell proliferative response to high concentrations of interleukin-2 (IL-2) is unlikely to be mimicked in vivo. The role of NK cells in infection is highlighted by the case of an adolescent woman with a selective NK cell deficiency in whom there were frequent, recurrent septicemic episodes due to uncontrolled viral infections, including cytomegalovirus (CMV), varicella-zoster virus, and herpes simplex virus. The NK cell compartment is not fully developed at birth, as indicated by lower natural killing by human cord blood lymphocytes and corroborated by studies on the ontogeny of NK cells in rodents. Classically, NK cells kill their targets by the triggered and directional release of preformed cytoplasmic granules containing perforin and granzymes, a process termed granule exocytosis. The role of NK cells in infection control is related to their receptors that regulate the natural killing function. The inhibitory receptors do not explain all aspects of NK cell specificity. As predicted by the two-receptor model, NK cell recognition also appears to involve activation receptors. The distribution of NK cells and recruitment therefore may be related to organ-specific differences in the NK cell effector mechanism controlling murine CMV (MCMV) replication.