抗小鼠TLR2抗体TSP-2抑制小鼠肥大细胞脱颗粒作用的初步研究

发布时间：2017-12-31 21:16

本文关键词：抗小鼠TLR2抗体TSP-2抑制小鼠肥大细胞脱颗粒作用的初步研究　出处：《第一军医大学》2006年博士论文　论文类型：学位论文

【摘要】：哺乳动物Toll样受体(Toll-like receptors，TLRs)是果蝇Toll的同系物，它们构成一个新的蛋白家庭家族，是一类与天然免疫关系密切的模式识别受体，参与天然免疫的介导并激活获得性免疫。其共同特点是胞外段有富含亮氨酸的重复结构域(LRR)，胞内段与IL-1受体具同源性；其信号转导主要经IL-1R相关激酶(IRAK)，导致NF-κB激活，继而产生细胞因子。自1997年发现第一个哺乳动物TLRs以来，迄今为止已发现TLRs分子约12个，即Toll 1-11和18-wheeler。研究表明，TLRs不仅参与天然免疫与感染免疫，还可参与非感染免疫及获得性免疫，如抗原递呈、诱导免疫耐受、细胞凋亡，并以此在自身免疫病、超敏反应、移植排斥及肿瘤免疫中发挥重要作用。而某些TLRs能诱导抑制或增强炎症反应的相关细胞因子如IL-10，IL-4，IL-5和IL-13的产生，这些细胞因子在炎症导致的病理损伤和机体防御中均起重要作用。目前认为过敏性疾病与Th2型T细胞产生的细胞因子密切相关，如Th2型细胞因子IL-4能诱导IgE的产生，IL-5可趋化嗜酸性粒细胞聚集；而与感染有关的Th1型细胞因子如IL-12、IFN-γ等则能抑制Th2型细胞因子的作用，从而抑制过敏反应的炎症反应。正如有人提出的卫生学假说，，幼儿及青少年时期发生感染机会减少则过敏症的发病率相应升高。哺乳动物的很多TLRs都参与了过敏性炎症过程，其中以TLR2、TLR4和TLR9研究较多：已知TLR2是人类TLRs家族成员中表达范围最广、识别病原微生物及其产物种类最多的分子，被认为是所有TLRs中具中心作用的或中枢型识别(central pattern recognition)受体。TLR2分子主要表达在单核细胞、巨噬细胞、树突状细胞、γ／δT、Th1、Th2α／βT，尤其在脾脏和外周血白细胞高表达，其次在部分消化道上皮细胞株、B细胞株及大鼠心肌细胞、脑组织、齿龈细胞等也有表达。尽管有许多实验证实了TLR2与一些配基相互作用参与了免疫相关事件，但是关于TLR2抗体的作用研究报道很少。另外，有很多研究表明肥大细胞膜上的TLR2在介导肥大细胞活化中发挥重要作用。
[Abstract]:The mammalian Toll like receptors (Toll-like receptors, TLRs) are homologues of Drosophila Toll, they constitute a new protein family, is a kind of relationship with the innate immune pattern recognition receptors which is closely involved in mediating innate immunity and acquired immunity. The activation of the common features is the repeat domain is rich in extracellular segment leucine (LRR), intracellular segment and IL-1 receptor homology; the major signal transduction by IL-1R related kinase (IRAK), resulting in NF- kappa B activation, and cytokine production. Since 1997, the first mammalian TLRs, so far it has been found that TLRs molecules of about 12, namely Toll 1-11 and 18-wheeler. research shows that TLRs is not only involved in innate immunity and immunity to infection, can also participate in non infection and acquired immunity, such as antigen presentation, immune tolerance induction, cell apoptosis, and thus in autoimmune disease, hypersensitivity, rejection and Play an important role in tumor immunity. Some TLRs can induce inflammation related cytokines such as IL-10, IL-4, IL-5 and IL-13, both play an important role in pathological damage and defense causes of these cytokines in inflammatory cytokines. The allergic disease and type Th2 T cells closely related, such as Th2 IL-4 type cytokines can induce the expression of IgE, IL-5 chemotactic eosinophilia; and Th1 infection related cytokines such as IL-12, IFN- r inhibited type Th2 cytokines, inflammatory reaction and inhibit the allergic reaction as the hygiene hypothesis. The children and adolescents, reduce the incidence of infection opportunity is allergy rate increased correspondingly. Many TLRs mammals are involved in allergic inflammation, including TLR2, TLR4 and TLR9 of: TLR2 is known to the human TLRs family members expressed in the widest range of molecular identification of pathogenic microorganisms and their products are considered to be the most species, with innate immunity in TLRs (central pattern recognition).TLR2 receptor molecule is mainly expressed in monocytes, macrophages, dendritic cells, gamma / delta T, Th1. Th2 alpha / beta T, especially high expression in spleen and peripheral white blood cells, in the second part of the digestive tract epithelial cells, B cells and rat myocardial cells, brain tissue, alveolar cells is expressed. Although there are many experiments confirmed the TLR2 and ligand interaction involved in immune related the event, but reports about the effect of TLR2 antibody is few. In addition, many studies have shown that mast cells on the membrane of TLR2 play an important role in the activation of mast cells in the medium.

【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392

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