Natural Killer (NK) Cells

Summary 

Natural Killer (NK) cells are a type of innate immune cell of lymphoid origin. Being part of the innate immune system, NK cells recognize and kill unhealthy cells by looking for non-specific abnormalities. NK cells are stimulated by interleukin-2, interleukin-12, and interferons alpha and beta. NK cells function by attacking or killing cells lacking MHC I, which is down-expressed by virally-infected and cancer cells. In addition, NK cells can also attack cells that are bound by IgG antibodies, in what is called antibody-dependent cell-mediated cytotoxicity (ADCC). In order to kill a target cell, NK cells release perforin and granzyme. Perforins open holes in the target cell membrane, which granzyme enters to induce cell death.

Key Points

• Natural Killer Cell (NK Cells)
  • Lymphocyte of the innate immune system
    • No antigen-specific activities; do not require exposure to an antigen for activation and do not possess antigen memory
  • Stimulated by
    • Interleukin-2 (IL-2)
      • Potent stimulator of proliferation in all lymphocytes; used to increase anti-tumor activity of NK cells in cancer
    • Interleukin-12 (IL-12)
    • Interferon alpha/beta (IFN-alpha/beta)
  • Produces Interferon gamma (IFN-gamma)
  • Activated by non-specific surface signals
    • Cells lacking MHC I
      • Seen in stress, cancer/malignancy, or viral infections
    • Cells with bound Immunoglobulin G (IgG)
      • Referred to as antibody-dependent cell-mediated cytotoxicity (ADCC)
      • CD16 expressed on NK Cells binds Fc region of bound IgG
  • Activation releases granules containing perforin and granzyme
    • Perforin forms pores in target cell membrane
    • Granzyme enters through these pores to induce cell death