Natural killer cytolytic activity

Natural killer (NK)-mediated cellular killing has been extensively studied over the past 35 years and the current "granule exocytosis" model integrates work from many investigators to outline the primary means of NK cytotoxicity. A secondary pathway is mediated through so-called death-receptors, and exhibits less relevance for host defense against pathogens in vivo but is important for the elimination of auto-reactive lymphoid cells and also homeostasis. NK cells directly execute the destruction of both autologous and allogeneic cells. NK cytotoxicity has a direct role in host defense and immunopathology in response to viral infection and malignant transformation. NK cells are heralded as the first wave of defense against a variety of pathogens in which they employ potent weaponry to kill infected and malignant cells. In addition to killing these "stressed" cells, NK are implicated in the elimination of autologous activated immune cells (T cells and macrophages) following an inflammatory response. Furthermore, NK are critical producers of cytokines, most notably the pro-inflammatory interferonγ (IFNγ), which has pleiotropic effects on cells that modulate the adaptive immune response. NK cells are the innate constituents of cytotoxic lymphocytes and they utilize identical cytolytic pathways as the CD8+ cytotoxic T lymphocytes (CTL), namely via granule exocytosis and death-receptor mediated killing. NK cells are considered part of the innate immune system due to their germ-line encoded, early and rapid cytolytic response to a diverse array of pathogens, although they do not kill "non-specifically". The simple fact that NK cytotoxicity can cause cell death demands strict regulation upon the activation of NK by potential target cells.