Natural Killer Cells: From Bone Marrow to Cytotoxic Cells

Natural killer (NK) cells are lymphoid cells, having central effector functions in immune system without previous sensitization. These cells are related to innate lymphoid cells which are characterized by lymphoid cell morphology with missing antigen- specific receptors. NK cells are defined by lack of expression of CD3 and expression of CD56 (CD3-CD56+). Based on the expression of CD56, human NK cells are classified into two main populations: CD56bright and CD56dim NK cells. Functionally, CD56bright subset is characterized by higher capacity to produce cytokines following activation but has lower cytotoxicity. On the contrary, CD56dim NK cells are more cytotoxic and express higher levels of maturation markers. NK cells have effective cytotoxic activity against virus-infected cells and tumors, and their effector functions are regulated by multiple activating and inhibitory receptors. The activated NK cells are able to kill their target cells in apoptosis process by different mechanisms, including cytolytic granule-dependent exocytosis pathway, death receptor pathway, antibody-dependent cell-mediated cytotoxicity, and the release of cytokines. This review will focus on NK cell differentiation, NK cell receptors as well as their ligands and their role in immune responses. In addition, we will summarize the pathways involved in NK cell effector functions.