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:
- First activation triggers the discharge of proteins contain in the natural killer cells and cytoplasmic granules towards the infected cells.
- 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.
- The net result of this reaction is that NKC kills infected cells.
- By killing infected host cells, NKC like cytotoxic T-lymphocyte eliminates cellular reservoir of infection.
- Secondly, macrophages ingest microbes and produce interleukin-12 (IL-12).
- Il-12 activates NKC to secrete interferon-gamma and interferon in turn activates macrophages to kill the ingested microbes.
- NKC can kill the cellular target without the prior expose to antigens of the target cells.
- Thus, they can directly kill tumor cells and virally infected cells without ingesting them.
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.
Natural killer cells (NKC)