The complete biochemical and physical analysis of the CD16 molecules that are expressed on the surface of the Natural killer cells or NK cells.
The CD 16 molecule if a low affinity Fc receptor. It is basically a cluster of differentiation molecule that is present or found on the surface of the natural killer cells, monocyts, macrophages and the neutrophil polymorphonuclear leucocytes. It can be utilized in isolating the populations of thee cells by using the antibodies that are directed towards the CD16 cells. The methodologies that can be used are fluorescent activated cell sorting or magnetic activated cell sorting (Janeway, C. 2001). CD16 receptors have been identified as the Fc receptors FcγRllla (CD16). The function of these receptors is to bind to the Fc region of the IgG antibodies which then cause the activation of the NK cells for the antibody dependent cell mediated cytotoxicity. If there is lack of CD16 cell receptors in the given population of cells (neutrophills, specifically), it may indicate prematurity which might be caused due to the left shift as a consequence of leukocytosis that may be induced by the tissue necrosis or the infection mediated by bacteria (Anderson et al. 1990).
One type of CD16 is CD16A, which is a transmembrane protein that is known to co localize with CD3ζ and Fc-εRI-γ on the surface of the NK cells. Upon ligation, the stimulus intiates a series of signals that help in the initiation of production of cytokines. The second type of CD16 is CD16B. This is found on the neutrophills. The two sub types of CD16 molecule can be differentiated on the basis of the glycosylphosphatidylinositol linkage. Even the extracellular domains of both these molecules are highly homologous. Most of the CD56 bright Nk cells do not show CD16A. But the down regulation of these cells happens after the mitogen stimulation and the coculture of the cells with the malignant targets (Romee et al. 2013).
The body’s defense system is governed by the host defense system and lymphocytes are the main type of cells that are involved. Natural Killer (NK) cells are the granular lymphocytes that help in fighting against tumor cells and also against the cells that are infected with virus. The NK cells are also related to the antibody mediated cytotoxicity that is mediated by the CD16 cells. Research has shown that CD16 cells are associated with the dimmers that are linked via dimmers that are composed of 2 homologous sub-units, gamma and zeta. These two subunits are kind of transducing molecules that are strongly associated with numerous other multimeric cell surface receptors like the T cell antigen receptor complex, also known as CD3:TCR complex (Vivier, E, Ackerly, M, Rochet, N and Anderson, P. 1992).
The CD16 molecule is the functional receptor structure that is present on the surface of the NK cells and is responsible for mediating antibody- dependent cell mediated cytotoxicity (ADCC). FcγRllla mediated activation of the NK cells causes the activation of the cytolytic activity and this further leads to increase in the intracellular concentration of the calcium, rise in the tyrosine phosphorylation of the regulatory proteins and even the secretion of the cytokines like TNFα and IFNγ. After the phosphorylation of the tyrosine residue and its activation post stimulation of the NK cells with the anti- CD16 monoclonal antibodies. Treatment with the anti CD16 monoclonal antibodies can initiate apoptosis of the IL-2 activated NK cells. Inspite of the presence of the CD16 cells, th eneutrophills cannot mediate the function of ADCC. Thus, research suggests that on the surface of granulocytes, the molecules of CD16 may act as adhesion structure that binds immune complexes allowinf for subsequent cellular activation by the other different types of FcR (Knowles, D. 2001).
The Fc receptor CD16 is generally located on all the CD56 (dim) peripheral blood NK (natural killer) cells. When it recognizes the antibody coated cells, it transmits a signal to the NK cells and they, in response to the signal, eliminate the target cells through direct killing or via production of cytokine.Researches have been conducted in order to study the change in the expression of CD16. The activation of CD56 along with the cross link of CD16 with the antibodies led to the loss of CD16 and CD62L and this was correlated with the increase in the production of interferon- γ (Romee et al. 2013). The activated NK cells lose CD16 through a metallo protease known as ADAM17. If ADAM17 is inhibited, this enhances the CD16 mediated NK cell function by preservation of CD16 on the surface of the Natural Killer cells and this as a result leads to enhancement of ADCC (Lanier, L., Ruitenberg, J. and Phillips, J. 1988).
Anderson, P., Caligiuri, M., Manley, T., Ritz, J. and Schlossman, S., 1990, Fc gamma receptor type III (CD16) is included in the zeta NK receptor complex expressed by human natural killer cells, Proc Natl Acad Sci U.S.A., 87(6): 2274-2278.
Janeway, C., 2001, Appendix II. CD Antigens, Immunology (5 ed.), Newyork:Garland.
Knowles, D., 2001, Neoplastic hematopathology, Lippincott William & Wilkins, P-150.
Lanier, L., Ruitenberg, J. and Phillips, J., 1988, Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes, The Journal of Immunology, 141(10): 3478-3485.
Romee R, Foley B, Lenvik T, Wang Y, Zhang B, Ankarlo D, Luo X, Cooley S, Verneris M, Walcheck B, Miller J., 2013, NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17), Blood, 121 (18):3599-608.
Vivier, E, Ackerly, M, Rochet, N and Anderson, P., 1992, Structure and function of CD16: zeta: gamma complex expressed on human natural killer cells, Int J Cancer Suppl., 7: 11-14.
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