Ronald B. Herberman

Cytotoxic Mechanisms of Natural Killer Cells

Publisher Summary This chapter focuses on the two cytotoxic mechanisms in natural killer (NK) cells: secretory/necrotic and nonsecretory/apoptotic killing. NK cells are cytotoxic effector cells of the immune system that have spontaneous ability to selectively kill virus-infected and tumor cells without damaging normal cells. The secretory/necrotic pathway model of killing is based on the hypothesis that NK cells, interacting with susceptible targets, are triggered via specific receptors to actively release cytolytic granules and molecules capable of damaging the target cell membrane. The nonsecretory/apoptotic pathway can kill a large variety of solid tissue-derived tumor cell targets. These pathways are mediated via ligand/receptor initiating signal transduction in either effector or target cells. The novel pathway is mediated by the tumor necrosis factor (TNF) family ligands and is highly promiscuous, which may be potentially important in immune surveillance, antimetastatic/antitumor functions, and immunoregulation.