New insights into the cell biology of human natural killer cells and cytotoxic function

Natural Killer (NK) cells are the main cytotoxic lymphocytes of the innate immune system. They utilize lysosome-related organelles (called lytic granules) loaded with perforin and granzymes to mediate the destruction of diseased cells. The process by which they kill is a highly coordinated series of cell biological steps in which the lytic granules are mobilized, polarized and then carefully provided access to the NK cell membrane so that their contents can be secreted. Our laboratory has been studying the cell biological regulation of the mechanics of this process and has also attempted to gain insights from genetic diseases of immunity. An overview as well as some new insights into the cell biological process of cytolytic function of NK cells will be presented as will be some lessons taught by novel and known genetic disease. As the cytolytic defenses mediated by NK cells are highly relevant to host defense against and even in treatment of cancer a better understanding of how NK cells kill will hopefully allow us to better harness their activities therapeutically.