Mechanisms of target cell killing by natural killer cells

Understanding of the lytic process of NK cells has been greatly advanced in the past decade. However, the definition of the primary event required for lysis has been elusive. The recent enthusiasm about the granule exocytosis/PFP model of membrane damage has been tempered by the multitude of factors that cytotoxic effector cells can secrete and the observation of rapid nuclear degradation before membrane damage which is not well explained by the PFP model. Logically, one would expect that this array of cytotoxic, cytostatic and immunoregulatory factors are secreted for a purpose, and should, therefore, be involved in the lysis of target cells. Further studies are necessary to define the role of each of these factors in plasma membrane and nuclear damage. Additional experiments to determine whether these two events are related will be necessary. On the basis of information currently available, one could hypothesize that after recognition of foreign cells, the NK cell is not single-minded in its delivery of lethal factors. The end result is that target cell lysis may occur because of many factors acting not only on the target cell itself but also on other components of the host immune response.