Natural Killer Cells

Type of CellLymphocyte
Produced? In the bone marrow
Where are they found?In the blood, bone marrow, liver, spleen, uterus, lung, SLT & MALT
FunctionDetect and kill virally infected cells and cancer cells through the release of cytotoxic molecules
SLT = Secondary Lymphoid Tissue MALT = Mucosal Associated Lymphoid Tissue

Natural Killer (NK) cells form part of the innate immune system. They were given the name “natural killer” cells because of their ability to kill abnormal cells without prior activation, unlike the other cells in the lymphocyte family. Their main functions are killing virally infected cells and targeting cancer cells.

There are four main steps involved in the NK cell cytotoxic response. The entire process is called degranulation and is used as an indirect measurement for the cytotoxicity of NK cells.

The first step is the formation of a synapse between the NK cell and the target cell. The NK cell expresses several types of receptors on its cell surface, the main two being an activating receptor and an inhibitory receptor. The activating receptor recognizes specific ligands on the surface of the target cell. The inhibitory receptor recognizes Major Histocompatibility Complex (MHC) class I ligands on the surface of the target cell. Normal, healthy cells express MHC class I molecules on their cell surface. Virally infected cells and cancer cells lose the ability to express these ligands on their cell surface. This enables NK cells to determine what is “self” and “non-self”. In other words, it can specifically target infected cells and leave healthy cells alone. The ability to distinguish between self and non-self is an important concept in immunology as it forms the basis of autoimmunity. In addition to the loss of MHC class I ligands, the products of cellular stress as a result of viral infection or tumour development can act as activating ligands for the NK cell. Activation of both the activating receptor and the are required for full NK cell activation.

The second step in the NK cytotoxic response involves the polarization of the microtubule organizing centre (MTOC) so that a secretory lysosome full of cytotoxic molecules can be brought towards the synapse created between the NK cell and the target cell. More on MTOCs in microtubules. This leads directly on to the third step, which is the docking of the secretory lysosome to the plasma membrane of the NK cell.

The fourth and final step is the release of the cytotoxic molecules through fusion of the secretory lysosome with the plasma membrane of the target cell. Perforin binds to the plasma memebrane of the target cell and creates pores in the cell surface. Granzymes then enter through these pores and induce apoptosis of the target cell, thereby killing it.

NK cells are important target in cancer immunotherapies because of their ability to detect and kill cancer cells. They are unique because of their ability to kill abnormal cells without prior sensitization and because they are so vital in immunosurveillance. There have already been several studies that have shown that the transfer of NK cells from an individual to a patient (adoptive transfer) was successful against several types of cancer. The ability of NK cells can also be enhanced by antibodies and other cytokines and chemokines.

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