NK cell-mediated target cell death

Publisher Summary The idea of cell lysis being the endpoint of all cell- mediated cytotoxic events can no longer be considered an accurate in vitro assessment or predictor of target cell death mediated by NK cells in vivo. The model in which a mast cell explodes and releases its highly inflammatory cytoplasmic contents represents a system decidedly biased towards an endpoint of target cell death that occurs rarely, if at all, in vivo. Despite recent advances in understanding molecular mechanisms of natural killer (NK) cell recognition of target cells and consequent target cell death, the gold standard for assessing successful effector–target interactions has not changed. Specifically, the idea of target cell lysis, a process that would result in inflammation in vivo, as representative of NK cell-mediated death does not accurately represent the quiet death that most targets undergo. Notably, the two main death pathways triggered by NK cells, the delivery of perforin/granzymes from NK cells to targets and the ligation of death receptors on target cells by proteins on NK cell surfaces, are engaged considerably upstream. Both lead to apoptotic death, a significantly different in vivo outcome than the release of cytoplasmic target cell contents would suggest. In this chapter, a discussion of alternative measurements based on recently established cell death signalling pathways is presented. As major effector cells of the innate immune system, natural killer (NK) cells are cytotoxic responders to pathogen-infected and tumor cells. These large granular lymphocytes are able to detect and destroy both directly and indirectly cells infected with a variety of viruses, bacteria and parasites as well as tumor cells of diverse histologic origin.