LPS刺激的小鼠骨髓来源树突状细胞生长和细胞周期分析

发布时间：2018-07-04 21:19

本文选题：树突状细胞 + 脂多糖　；参考：《第二军医大学》2005年硕士论文

【摘要】：树突状细胞(DC)是目前已知的功能最强的专职抗原提呈细胞。它们在体内广泛分布于血液、肝、脾、淋巴结以及其他非免疫组织器官中并有各自的名称:如淋巴器官中的并指状细胞,血液中的单核细胞和表皮中的郎罕氏细胞。DC具有多种不同的形态、表型和功能。已知DC的功能特点与其不成熟(immature)和成熟(mature)状态密切相关:总体上讲,不成熟的树突状细胞具有高效的抗原摄取、处理功能,呈非活化状态。因为表达共刺激分子和MHC水平较低,不成熟树突状细胞对T细胞的激活作用较弱。遇到感染信号后,不成熟树突状细胞摄取、处理外来抗原,经历一个分化成熟过程并且迅速表达大量共刺激分子和稳定的MHC而转变为成熟状态。此时树突状细胞的抗原提呈功能大大增强,而抗原摄取能力已大大降低,它们会迁移到淋巴器官刺激和活化初始T细胞增殖。树突状细胞系统包括许多功能不同的亚群。按照表型和功能可以把小鼠树突状细胞的分为六个主要亚群:CD8~-DC、CD8~+DC、CD8~intDCs、朗罕氏细胞(Langerhans cells)、皮肤DCs(Dermal DCs)和类浆细胞(B220~+)DCs。每个亚群有不同的功能。例如,在体外Fas诱导T细胞凋亡时,CD8~-DCs会引起CD4~+T细胞产生强烈的增殖反应,而CD8~+DCs诱导的反应相对较弱。B220~+DCs通过诱导调节性T细胞的分化来介导T细胞耐受。还有人报道不成熟DC也可以通过诱导调节性T细胞的分化间接引起T细胞失能和耐受;而同一批不成熟DC(imDC),接受了刺激信号后即分化成熟,从而启动效应性T细胞的活化。由于树突状细胞在初次免疫应答中所扮演的重要角色,研究DC在肿瘤免疫和免疫耐受中的调节作用有重大意义。 DC的不同成熟阶段和成熟过程是被精确而有效地调控着的。根据他们在微环境接受的精确信号,DC可以达到不同的活化状态以及不同的成熟状态从而发挥不同的功能。DC的成熟可以由多种刺激物触发,包括接触性变态反应原,细菌和病毒,白细胞介素-1(interleukin-1,IL-1)、IL-6、肿瘤坏死因子α(TNF-α)等促炎症细胞因子,未甲基化CpG、poly(I:C)等免疫刺激物,信号分子CD40L等等。脂多糖(Lipopolysaccharide,LPS)是革兰氏阴性细菌胞壁组分,是DC(包括
[Abstract]:Dendritic cells (DC) are the most functional antigen presenting cells. They are widely distributed in the body in blood, liver, spleen, lymph nodes, and other non-immune organs and have their own names: such as syndactyls in lymphoid organs, Monocytes in the blood and Langham cells in the epidermis. DC have many different morphologies, phenotypes and functions. The functional characteristics of DCs are closely related to their immature (immature) and mature (mature) states: in general immature dendritic cells have high antigen uptake processing function and non-activated state. Because of the low expression of costimulatory molecules and MHC, immature dendritic cells have weak activation of T cells. After infection, immature dendritic cells ingest, process foreign antigens, undergo a process of differentiation and maturation, and rapidly express a large number of costimulatory molecules and stable MHC to mature state. At this time, the antigen presentation function of dendritic cells is greatly enhanced, and the ability of antigen uptake has been greatly reduced. They migrate to lymphoid organs to stimulate and activate the initial T cell proliferation. The dendritic cell system consists of many subgroups with different functions. According to its phenotype and function, mouse dendritic cells can be divided into six main subgroups: CD8 ~ DCN CD8 ~ DC8 ~ DC8, Langerhans cells), skin DCs (Dermal DCs) and plasmacytes (B220 ~) DCs. Each subgroup has different functions. For example, when FAS induces T cell apoptosis in vitro, CD8- DC can induce strong proliferation of CD4T cells, while CD8- DCs induce relatively weak response. B220- DCs mediate T cell tolerance by inducing regulatory T cell differentiation. It has also been reported that immature DCs can also induce T cell inactivation and tolerance indirectly by inducing regulatory T cell differentiation, while immature DCs (imDCs), after receiving stimulation signals, differentiate and mature, thus initiating the activation of effector T cells. Because of the important role of dendritic cells in the primary immune response, It is of great significance to study the regulatory role of DC in tumor immunity and immune tolerance. The different mature stages and processes of DC are precisely and effectively regulated. Depending on the precise signal they receive in the microenvironment, DC can reach different activation states and mature states so that they can perform different functions. DC maturation can be triggered by a variety of stimuli, including contact allergens, bacteria and viruses. Interleukin-1 (IL-1) IL-6, tumor necrosis factor- 伪 (TNF- 伪) and other pro-inflammatory cytokines, unmethylated CpG- (I: C) and other immune stimulators, signal molecules CD40L and so on. Lipopolysaccharide (LPS) is a component of the cell wall of gram-negative bacteria and is DC (including
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

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