Role of Natural Killer Cells in Innate Antiviral Immunity - Essay Example

? Role of NK Cells in Innate Antiviral Immunity Role of NK Cells in innate antiviral immunity Natural Killer cells, commonly referred to as NK Cells are part of the cytotoxix lymphocyte which is critical in the innate immune system of the human body (Pyzik & Vidal, 2009). These cells play a similar role to that played by cytotoxic T Cells in adaptive immune response among vertebrates. The Natural Killer (NK) cells provide quick responses to cells infected by viruses and also respond to formation of tumors. The cells become active and start working at around three days after an infection has occurred. Unlike other immune cells that detect MHC on the surfaces of infected cells to trigger the release of cytokine so as to cause apoptosis or lysis, the NK cells are unique in that they have the ability to identify affected cells without the presence of MHC and other antibodies. This allows them to react much faster as compared to the other immune cells. Their name, ‘natural Killers” is derived from the fact that these cells do not need to be activated in order to kill the cells that are lacking the self markers of MHC (Major Histocompatibility Complex) class 1. The innate immune system is also referred to as non-specific immune system and comprises of various mechanisms and cells which defend hosts from being infected by other organisms in ways that are not specific (Janeway, 2005). This implies that the cells in this immune response system identify and respond to the pathogens. This is different from the adaptive immunity which only exists in vertebrates and does not guarantee longer protection of the host from infections. Innate immunity on the other hand ensures early defense against viral infections and is found in both plants and animals. The innate immunity is more common in plants, insects and fungi as well as in multi-cellular organisms and constitutes evolutionary defense mechanisms. Among vertebrates, the innate immune system plays a range of functions, among them; activating cells to foster clearance of antibody complexes or dead cells, activating the adaptive immune system in a process referred to as antigen presentation, identifying and removing foreign substances that may be found in tissues, organs, blood, and the lymph through the use of white blood cells, sending immune cells to areas that have been infected through production of cytokines to respond to body infections and acting as both chemical and physical barriers to any agents that may cause infections to the host’s body (Lotze & Tracey, 2005). The natural killer cells can also be described as larger granular lymphocytes (LGT) and comprise of the third type of cells that are differentiated from the commonly known lymphoid progenitor, which generates the B cells and T lymphocytes (Doan, 2008). The NK cells grow and mature in the spleen, bone marrow, tonsils, lymph node and the thymus, where they are allowed to get through in to the blood circulation. NK cells have are phenotypically differentiated from another group of immune cells known as the Natural killer T cells (NKT Cells). These two types of cells differ from each other from their origin and also by their respective effector roles. The activities of NKT cells assist the NK cells through secretion of immunoglobulin (lb) B cell receptors albeit they normally express CD16 surface markers and CD56 among human beings and NK1.1 among C57BL/^ Mice. Most of the NK Cells in human beings also produce CD 8 (Lodoen & Lanier, 2005). Natural Killer cells are widely known for their function as effectors in the innate immunity. Recent studies have however revealed further roles that both inhibitory and activating cells play in the body including functions such as self tolerance as well as sustaining and maintaining NK Cell activity. The natural Killer cells also have an important function in adaptive immune response. There are various scientific studies and experiments that demonstrate the ability of the NK cells to readily to their immediate surroundings and formulate immunological memory that is specific to particular antigens, and is fundamental in the response to secondary infections resulting from the same antigen. This ability for NK cells to function in both adaptive and innate immune response is generating a lot of interest among scientists and is forming a greater part of recent and contemporary studies utilizing potential cancer therapies and activities of NK cells. NK cells play a very essential role in immune responses against tumors and other pathogens. Most studies in the past decade seemed to focus on identifying the cell surface effectors and receptor molecules used by the Natural killer cells in recognizing target cells and destroying them. Much of the attention has been shifted to the determination of the function that NK cells play in innate immunity as well as their contribution to adaptive immune response. Despite the fact that most of the NK inhibitory and activating receptors as well as their signaling pathways and ligands have been discovered, There are still many issues that have not been addressed such as the scientific importance of the molecules in defending the hosts, how these molecules are regulated during their development and clarification of how the NK cells interact with other hematopoietic cells. These are issues that scientists are focusing their attention in their studies to try and address them. NK cells have various essential functions to play in innate antiviral immunity. The NK cells have the capability to kill young dendritic cells (DCs) just lime they kill other cells that they target. The two types of cells also have a good relationship between themselves as they reciprocate to activate each other in immune response (Bulmer, J, Williams, P, Lash, G 2010). Fist, the dendritic cells activate resting NK cells to help them initiate their activities and respond to pathogens and tumors that have infected hosts. The dendritic cells release various cytokines including IL-18 and IL-12 that are necessary for activation of NK effector. The stage of maturity of the dendritic cells will influence their ability to activate NK cells. Immature DCs will need a maturation stimulus before they can activate NK cells. The relevance of this activation can be illustrated in viral models and murine tumors. The CD8a-DC subset can be seen in both cases, indicating the role of DCs in the whole process. The NK cells also contribute in activating the dendritic cells during the antiviral immune response. The DCs are either activated or matured through their reciprocal interactions with the NK cells, as seen through the measurement of production of DC cytokines, the ability to stimulate responses from T cells or the induction of stimulatory molecules between them. Optimal activation of DCs often results to production of TNF-a. It is however not clear whether resting NK cells can activate DCs. The interaction between the two cells occurs in both in vitro and in vivo. The Natural killer cells play a very important role in eradication of viral infections. The cells are often activated immediately after an infection with both bacterial pathogens and viruses. Viruses have developed mechanisms to interfere with normal functions of NK cell effectors. In both mice and human beings, the NK cells are required to control herpesyiviruses. The involvement of NK cells in antiviral immunity can be seen in the case of CMV, which is a part of the herpersvirus family. Depletion of Natural Killer cells in mice makes resistant mice more susceptible to being infected with MCMV. Recent studied have shown involvement of two types of NK cells receptors, namely NKG2D and Ly49H, in the recognition of cells infected with CMV. The NK cells need to have proper mechanisms in place for them to act effectively against pathogens and viruses. These mechanisms will help them to determine whether cells have been infected or not. Studies are currently underway to determine the exact mechanisms that facilitate this process (Tracey, 2009). It is however recognized that the NK cells adopt a state referred to as an “altered self”. In order to be able to control their cytoxic activity, the natural killer cells are, are up of two kinds of surface receptors namely the inhibitory and activating receptors. This also includes other receptors that resemble killer cell immunoglobulin. Most of these receptors can also be found in other cells such as T cell subsets and are therefore not unique to NK cells. NK cells contain low levels of MCH class 1 molecules because of the Inhibitory receptors that are helpful in recognizing MCH Class I Alleles. The MCH Class I molecules act as the means through which cells show tumor antigens or viral to cytotoxic T cells (Tracey, 2007). This is can be observed in both tumors and intracellular microbes. In this evolutionary adaptation, the chronic down regulation of MKC L Molecules renders the cell impervious to immunity mediated by T cells. Most scholars believe that Natural Killer cells evolved as a response to this kind of adaptation. The depletion of MHC denies CD4/CD8 action so other immune cells evolved to play this function. References Arina, A., Murillo, O., Dubrot, J., Azpilikueta, A., Alfaro, C., PArez-Gracia, J.,L., Bendandi, M., Palencia, B., HervA?s-Stubbs, S. & Melero, I. (2007). "'Cellular liaisons of natural killer lymphocytes in immunology and immunotherapy of cancer'". Expert Opinion on Biological Therapy 5: 599–615. Bulmer, J, Williams, P, Lash, G. 2010. Immune cells in the placental bed. Int J Dev Biol 54: 281–294. Doan, T. 2008. Immunology. Lippincott Williams & Wilkins. Iannello, A., Debbeche, O., Samarani, S., Ahmad, A. 2008. "’Antiviral NK cell responses in HIV infection: I. NK cell receptor genes as determinants of HIV resistance and progression to AIDS’". Journal of Leukocyte Biology 84: 1–26. Janeway, C. 2005. Immunobiology. (6th ed.). Garland Science. Lash, G, Robson, S, Bulmer, J. 2010. "Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua". Placenta 31 (S): 87–92. Lotze, M. T; Tracey, K. J 2005. "High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal". Nature reviews. Immunology 5 (4): 331–42. Lodoen, M.,B. & Lanier, L.,L. 2005. "Viral modulation of NK cell immunity". Nature Reviews Microbiology 3: 59–69. Tracey, K. J. 2007. "Physiology and immunology of the cholinergic antiinflammatory pathway". The Journal of Clinical Investigation 117 (2): 289–96. Tracey, K. J. 2009. "Reflex control of immunity". Nature reviews. Immunology 9 (6): 418–28. Roitt I, Brostoff J, Male, D 2001. Immunology (6th ed.), 480p. St. Louis: Mosby, Terunuma, H., Deng, X., Dewan, Z., Fujimoto, S., Yamamoto, N. (2008). "Potential role of NK cells in the induction of immune responses: implications for NK cell-based immunotherapy for cancers and viral infections". International Reviews of Immunology 27: 93–110. Pyzik, M. & Vidal, S., M. 2009. "'NK cells stroll down the memory lane'". Immunology and Cell Biology 87 (4): 261–263. Vivier, E., Raulet, D.H., Moretta, A., Caligiuri, M.A., Zitvogel, L., Lanier, L.L., Yokoyama, W.M. & Ugolini, S. 2011. "Innate or Adaptive Immunity? The Example of Natural Killer Cells". Science 331: 44–49. Read More