In fact, this ‘spontaneous’ cytotoxicity of NK cells formed the basis for their discovery in the 1970s, when investigators tried to explain the presence of cytotoxic effects of lymphocytes against tumor cells in nonimmunized experimental mice. NK cells are large granular lymphocytes, which respond spontaneously to cells under insult using their germline-encoded receptors and require no prior exposure to antigen. NK cells are the major cellular effectors of the innate immune system, which function alone or in synchrony with other immune cells, to abrogate a variety of targets including virally infected and transformed cells as well as those under stress or heat shock. While tracing the remarkable properties of NK cells and the major developments in this field, we highlight the role of immune cooperativity in the betterment of current immunotherapeutic approaches. Various modes of NK cell manipulation are being undertaken to overcome issues such as relapse and graft rejections associated with adoptive immunotherapy. Endogenous expansion of NK cells and their effector mechanisms are under exploration for enhancing adoptive immunotherapy prospects in combination with immunostimulatory and cell-death-sensitizing treatments against cancer, viral infections and other pathophysiological autoimmune conditions. The battery of receptors possessed by NK cells help them to efficiently detect aberrant and infected cells and embark on the signaling pathways necessary to eliminate them. Increased evidence of cross-talk between NK cells and other immune cells has enhanced the possibilities of exploiting the interplay between the activation and inhibition of NK cells for immunotherapeutic purposes.
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