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The Influence of Innate Immune Molecules and Cells in the Pathogenesis of Autoimmune Disease in Central Nervous System

Author: YangYan
Tutor: ZhengFang;GongFeiLi
School: Huazhong University of Science and Technology
Course: Immunology
Keywords: Multiple sclerosis Tumor Necrosis Factor Meta-analysis Gene polymorphism Natural killer cells Experimental autoimmune encephalomyelitis
CLC: R392
Type: Master's thesis
Year: 2011
Downloads: 23
Quote: 0
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Background: Multiple sclerosis (multiple sclerosis, MS) is a central nervous system autoimmune disease, environmental factors and genetic factors involved in the occurrence and development of MS disease. Tumor necrosis factor α (tumor necrosis factor-α, TNF-α) gene is one of the genetic factors involved in the decision to MS susceptibility. There have been many studies TNF-α promoter clinical case - control study of the relationship between the sub -308 locus gene polymorphism with MS susceptibility, but the conclusions of these studies are not consistent, so the need for a system of mathematical methods to analysis in order to get more accurate results. The EAE (experimental autoimmune encephalomyelitis), a good simulation of the human an animal model of the disease process of MS is itself MOG (myelin oligodendrocyte glycoprotein)-specific T cell-mediated autoimmune disease. Natural killer (natural killer, NK) cells are innate immune cells, plays an important immune surveillance and immune defense role, NK cells can regulate acquired immunity, plays an important role in the occurrence and development of EAE. NK cells in EAE also need to further clarify the role for early development and the various roles played by the different NK subsets. The purpose of: (1) using a meta-analysis method to study the relationship between the TNF-α-308 G / A polymorphism with MS susceptibility; (2) research and of EAE development of the early stages of NK cell changes, and NK cells against The regulatory role of innate immune cells and immune cells. Methods: (1) the development of standards, selected the 13 studies on TNF-α-308 G / A polymorphism and MS susceptibility, calculate the combined OR values ??and 95% confidence interval (confidence interval, CI). (2) Use of MOG (myelin oligodendrocyte glycoprotein) polypeptide joint Freund's complete adjuvant and active immunization of mice, the induction of EAE model. Cleared by immunization before the change of the innate and acquired immune cells in mice NK observe the the EAE progression of assessment NK role in EAE, flow detection NK cleared. Results: (1) Meta-analysis of selected research including of 1870 copies cases and 2769 controls. OR values ??of the combined incidence of TNF-α-308 A allele and MS has a significant negative correlation (A vs. G, p = 0.022). AA GA vs. GG (p = 0.008) and GA vs GG (p = 0.007) obtained similar results. GG or AA vs AA vs. GA GG no significant statistical significance, this may be because the AA genotype frequency is too low or not detected in some studies. (2) cleared before immunization mice NK will alleviate EAE disease severity; EAE progress early in the draining lymph nodes NK increase, reducing the proportion of CD27low NK subsets; the NK surface of NKG2D expression decline of NKG2D ligands RAE-1 in DC and Mφ downregulated; clear NK, DC and Mφ CD80 and CD86 expression down draining lymph nodes in Th17 reduced response. Conclusion: (1) TNF-α-308 A allele crowd, MS the risk is lower. (2) development early in EAE, NK cells may promote Th17 responses by stimulating APC cells mature to promote the development of the disease, CD27low NK subsets and NKG2D its ligand RAE-1 may be involved.

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