Natural killer cells (NKC)

Introduction of Natural Killer Cells

  • Natural killer cells are class of lymphocytes that respond to intracellular microbes by killing the infected cells and by producing macrophage activating cytokines.
  • They comprise about 10% of the lymphocytes in the blood and peripheral lymphoid organs.
  • These cells contain abundant cytoplasmic granules and express characteristic markers but they do not express immunoglobulins or T-cell receptors and the antigen receptors of B and T lymphocytes.
  • For this reason, they are also called as null cells.
  • They recognize infected cells that have been altered by microbial infection (microbes).
  • They express various receptors for molecules on host cells and some of the receptors activate the NKC and some of them inhibit the NKC.
  • The activating receptors are those that recognize the cells surface molecules that are commonly expressed on host cells.
  • Those molecules are present in the cells which are infected with viruses or the phagocytes harbouring viruses and intracellular bacteria.
  • Other activating NKC receptors recognize normal host cells surface molecules which could theoretically activate NKC to kill normal cells.
  • This does not usually occur because NKC also express inhibitory receptors that recognize normal host cells and inhibit the activation of NKC.
  • When NKC are activated they respond in two ways:
  1. First activation triggers the discharge of proteins contain in the natural killer cells and cytoplasmic granules towards the infected cells.
  2. These NKC granules proteins (perforins, graenzymes) include molecules that create holes in the plasma membrane of infected cells and other molecules as well as activated enzymes that induce apoptotic death.
  3. The net result of this reaction is that NKC kills infected cells.
  4. By killing infected host cells, NKC like cytotoxic T-lymphocyte eliminates cellular reservoir of infection.
  5. Secondly, macrophages ingest microbes and produce interleukin-12 (IL-12).
  6. Il-12 activates NKC to secrete interferon-gamma and interferon in turn activates macrophages to kill the ingested microbes.
  7. NKC can kill the cellular target without the prior expose to antigens of the target cells.
  8. Thus, they can directly kill tumor cells and virally infected cells without ingesting them.

 

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Functions of natural killer cells

  • Cytolytic granule mediated cell apoptosis.
  • Antibody-dependent cell-mediated cytotoxicity.
  • Cytokine induced NK and cytotoxic T-lymphocyte (CTL) activation.
  • Missing ‘self’ hypothesis.
  • Tumor cell surveillance.
  • NK cell function in pregnancy.
  • NK cells evasion by tumor cells.
  • Memory NK cells.

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References: 

i) https://www.immunology.org/public-information/bitesized-immunology/cells/natural-killer-cells

ii) https://www.nature.com/articles/ni1582

Natural killer cells (NKC)