The Role of NK Cells in Innate Anti-Viral Immunity - Essay Example

? NATURAL KILLER CELLS Natural Killer Cells Discuss the role of NK cells in innate anti-viral immunity and explain how NK cells are able to kill many types of virus-infected cells and not normal host cells. Natural killer cells are an important part of the innate immune system of the human beings. They are basically lymphocytes that are large and granular and constitute approximately 15% of the total lymphocytes in the circulation. These cells do not have T cell receptors as well as CD3 proteins. The immunoglobulins IgM and IgD are also not present on their outer surface. These cells develop in the human beings with the assistance of Interleukin 15 and they arise from the bone marrow through the CD34 cells which are hematopoietic stem cells. The natural killer cells do have a few T cell markers but unlike the T lymphocytes, thymus is not required for the maturation of the natural killer cells (Levinson 2008 p. 421). Another important aspect which is unique to these cells is that their quantity does not reduce in pathologic conditions which involve T Cells like Severe Combined Immunodeficiency Disease. Natural killer cells are referred to as “natural” owing to the fact that they can function without having any previous interaction with the virus and their non-specificity as they can act on all viruses. Also their efficiency is not improved by previous infections. These cells have an important function of protecting the body against viruses and this is proved as humans who do not have natural killer cells in their body have a higher susceptibility to develop lethal viral infections which include varicella zoster virus and cytomegalovirus (Hoffman et al 2013 p. 210; Levinson 2008 p. 421,422). Natural killer cells are an important constituent of the innate immunity and are amongst the first immune cells to reach the areas of inflammation and initiate an immune response. They are larger in size as compared to the B and T cells which is owing to the greater amount of cytoplasm in these cells which is composed of granules containing cytotoxic substances. These granules along with the substances within them are known to be identical to the granules of cytotoxic CD8 T lymphocytes (Lambris 2007 p.7). A significant role of these cells is that they come into action in an infection before the activation of T cells. It is also known that these cells are the first producers of interferon gamma. This prompt response of natural killer cells is noteworthy because individuals who have properly functioning T cell responses but lack natural killer cells have a tendency to develop fatal viral infections (Lambris 2007 p.7; Marsh et al 2000 p.46). Natural killer cells mainly follow two pathways for attacking and destroying the cells that they target. The first pathway is the cytotoxic granule dependent pathway. In this process, the receptors of the natural killer cells bind to the cells that are infected by viruses. This attachment promotes the secretion of perforin as well as granzymes that are present within the cytotoxic granules of the natural killer cells. Perforin is a protein that has a role in creating pores whereas granzymes are a group of proteases. Perforin acts on the membrane of the cell infected by the virus and creates pores, forming a passage for the granzymes into the attacked cell. The granzymes in turn activate the caspase protease system by either direct activation or by the production of Cytochrome c within the mitochondria which then leads to the apoptosome path for the initiation of the caspase system. Thus, this activation of the caspase protease system results in the cell death and destruction of infected cells. The second path that is used by the natural killer cells for the induction of apoptosis of the cells infected with viruses is known as the death receptor pathway. The natural killer cell memranes have the Fas ligand bound to them. In this path, the natural killer cells uses these ligands leading to the trimerization of the Fas receptors which are loacted on the outer membrane of the infected cells. This attachment to the Fas receptors results in the activation of the FADD adaptor protein and this is accompanied by the activation of caspase 8. The caspase 8 then begins the activation of the caspase either directly or by the apoptosome route. Thus, this leads to initiation of the process of apoptosis in the attacked cells (Delves et al 2011; Rich et al 2013 p.216). The natural killer cells also have surface molecules which aid in their functions. CD 16 is one such molecule. The IgG can serve as a ligand for this CD 16 and virus infected cells which are covered by IgG can be acted upon by the natural killer cells due to this molecule. This property of natural killer cells which allows it to lead to a lytic action on cells that are coated by IgG is referred to as antibody-dependent cell-mediated cytotoxicity (ADCC) (Kumar et al 2005 p.201; Colledge et al 2010 p.73). The natural killer cells possess the special characteristic of being able to distinguish the cells of the body from the cells which are infected and thus carry out its immune response against the anti viral cells. MHC class I proteins serve as the main identifiers on the target cells for this purpose. The natural killer cells are able to identify the cells which lack the MHC class I protein and hecen target them with their immune response (Hoffman et al 2013, p. 211). This is possible owing to the fact that MHC class I proteins act as ligands for the receptors of inhibition present on the natural killer cells and hence the immune response of the natural killer cells is inhibited against the normal cells. This characteristic is possible due to the interplay of various receptors that are present on these cells. These receptors hcan either activate or inhibit the immune response and it is brought about by the ligands of the target cells on which the natural killer cells act. These receptors include killer immunoglobulin like receptors (KIR) and CD 94 attached with a lectin subunit which is known as NKG2 (Brandstadter and Yang 2011, p. 274). The receptors like NKG2 and KIR have domains present within their cytoplasm which are known as immunoreceptors tyrosine based inhibitory motifs (ITIMs). When these receptors attach to the MHC class I molecules, the enzyme tyrosine phosphatase is activated within the natural killer cells. These phosphatases detach the phosphates which are present on the tyrosine of substances within the cells and this in turn prevents the action of kinases which are present on the ITAMs. This leads to the down regulation of natural killer cells and hence the normal cells of the body are spared from the action of the natural killer cells. But when cells that are infected with viruses are present within the circulation, this mechanism does not function for the infected cells. This is because virus cells do not have class I MHC molecules and thus they cannot inhibit the natural killer cells. This leads to the functioning of the natural killer cells against the viral cells and the activation of the kinase system which results in the destruction of the infected cells (Bhattacharya and Sinha 2006 p. 28; Brandstadter and Yang 2011, p. 276). Natural killer cells are important cellular components of the innate immune system. These cells serve to be the first immune cells activated in response to the virus infection in the body. This prompt response is of significance and fatal diseases can result due to the lack of natural killer cells in the body. These cells possess an important characteristic that is they can differentiate the normal cells from the virus infected ones. The MHC class I molecules on the cells serve to assist them in this purpose (Levinson, 421-422). This action is possible by the natural killer cells due to the presence of various receptors which inhibit the immune response of the natural killer cells against normal bodily cells. Bibliography BHATTACHARYA, S. & SINHA, J.K. (2006). A Textb0ook of Immunology. Academic Publishers. BRANDSTADTER, J. D., & YANG, Y. (2011). Natural Killer Cell Responses to Viral Infection. Journal of Innate Immunity. 3, 274-279. COLLEDGE, N. R., WALKER, B. R., RALSTON, S. H., & DAVIDSON, S. (2010). Davidson's principles and practice of medicine. 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