靶向DC-SIGN的抗原特异性免疫应答研究
发布时间：2018-10-17 14:38
【摘要】： 尽管疫苗的出现已经有效的改善了人类的健康进程,但对疫苗的设计仍有诸多改善的必要,尤其在各种新的感染性疾病层出不穷,癌症死亡率仍步步攀升的今天。因此,采取新的策略来改善疫苗的免疫原性,设计更为有效的治疗性疫苗是当前刻不容缓的问题。 树突状细胞(dendritic cells, DCs)是目前已知的功能最强大的职业抗原呈递细胞(profesional antigen presenting cells, pAPCs),能以受体介导的内吞、巨吞饮和吞噬等方式高效的摄取外界抗原并以多种机制来呈递抗原;作为一个自然的免疫佐剂,在遭遇危险信号时能高表达CD80、CD83、CD86等共刺激分子,与MHC抗原肽复合物共同作用可有效的活化效应T细胞,并且是唯一能活化na?ve T细胞的抗原呈递细胞;在静息状态(steady state)的DCs细胞仍然可以有效的“抽样调查(sample)”外界抗原,并组成性的呈递(constitutive presentation)这些无害的外来抗原和自身抗原(30-80%为自身合成缺陷的蛋白),通过诱导调节性T细胞分化来诱导和维持外周耐受; DCs细胞兼具两种看似矛盾的功能,正是通过它对“自身”和“非自身”抗原的判断来决定免疫系统的不同反应,在适当的时候产生适当的应答或是耐受,从而维持机体免疫稳态;因此,利用DCs细胞来调控和改善治疗性疫苗的免疫效应,上调或是下调特定的免疫反应,一贯是治疗性疫苗设计的重要方向。 DCs细胞虽然具有强大的摄取抗原的功能,但它对抗原非特异的摄取和呈递的方式会造成疫苗不能被有效呈递,从而影响疫苗的后续效应。将抗原靶向DCs,利用DCs来改善疫苗的免疫原性是重要的疫苗设计策略。随着分子免疫学和DC细胞生物学的进展,许多在DC特异表达的分子被鉴定,寻找适当的靶向途径成为一个历久弥新的重要课题。 新近发现的一些DC限制性表达的凝集素受体成为目前关注的靶向新途径,例如DEC205和DC-SIGN。DC-SIGN(DC-specific intracellular adhesion molecule-grabbing nonintegrin)受体是2002年发现的限制性表达于DC和某些组织巨噬细胞上的凝集素样受体, DC-SIGN已经被证实不仅是病原体受体,而且是重要的抗原受体,可有效的摄取处于粘膜组织的微量的HIV和CMV病毒颗粒,继之可以MHC-I类分子和MHC-II
[Abstract]:Although the emergence of vaccines has effectively improved the human health process, but the vaccine design is still necessary for many improvements, especially in the emergence of various new infectious diseases, cancer mortality is still rising step by step today. Therefore, it is urgent to adopt new strategies to improve the immunogenicity of vaccines and to design more effective therapeutic vaccines. Dendritic cell (dendritic cells, DCs) is one of the most powerful occupational antigen-presenting cells known at present. (profesional antigen presenting cells, pAPCs), can efficiently ingest external antigens by receptor-mediated endocytosis, giant swallowing and phagocytosis and present antigens through various mechanisms. As a natural immune adjuvant, CD80,CD83,CD86 and other costimulatory molecules can be highly expressed in the presence of danger signals. The interaction with MHC antigen peptide complexes can effectively activate the effector T cells and is the only antigen-presenting cell that can activate na?ve T cells. DCs cells in resting (steady state) can still be effectively "sampled to investigate (sample)" external antigens. In addition, compositional presentation of (constitutive presentation), a harmless foreign antigen and autoantigen (30-80% is a self-synthetic defective protein), induces and maintains peripheral tolerance by inducing regulatory T cell differentiation. DCs cells have two seemingly contradictory functions. It is through its judgment of the "self" and "non-self" antigens that it determines the different responses of the immune system and, at the appropriate time, produces an appropriate response or tolerance, thereby maintaining the immune homeostasis of the body; therefore, DCs cells are used to regulate and improve the immune response of therapeutic vaccines, upregulating or down-regulating specific immune responses. It has always been an important direction in the design of therapeutic vaccines. Although DCs cells have a strong ability to ingest antigens, However, the nonspecific way of uptake and presentation of antigens will result in the vaccine being unable to be effectively presented, thus affecting the subsequent effects of the vaccine. Using DCs to improve the immunogenicity of DCs, is an important vaccine design strategy. With the development of molecular immunology and DC cell biology, many molecules specifically expressed in DC have been identified. Recently discovered lectin receptors, which are restricted by DC, have become a new target pathway. DEC205 and DC-SIGN.DC-SIGN (DC-specific intracellular adhesion molecule-grabbing nonintegrin) receptors, for example, are lectin-like receptors found in 2002 that are restricted to DC and certain tissue macrophages. DC-SIGN has been shown to be not only a pathogen receptor, but also an important antigen receptor. Effective uptake of microamounts of HIV and CMV virus particles in mucosal tissue, followed by MHC-I molecules and MHC-II
【学位授予单位】：第三军医大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392
本文编号：2276998
[Abstract]:Although the emergence of vaccines has effectively improved the human health process, but the vaccine design is still necessary for many improvements, especially in the emergence of various new infectious diseases, cancer mortality is still rising step by step today. Therefore, it is urgent to adopt new strategies to improve the immunogenicity of vaccines and to design more effective therapeutic vaccines. Dendritic cell (dendritic cells, DCs) is one of the most powerful occupational antigen-presenting cells known at present. (profesional antigen presenting cells, pAPCs), can efficiently ingest external antigens by receptor-mediated endocytosis, giant swallowing and phagocytosis and present antigens through various mechanisms. As a natural immune adjuvant, CD80,CD83,CD86 and other costimulatory molecules can be highly expressed in the presence of danger signals. The interaction with MHC antigen peptide complexes can effectively activate the effector T cells and is the only antigen-presenting cell that can activate na?ve T cells. DCs cells in resting (steady state) can still be effectively "sampled to investigate (sample)" external antigens. In addition, compositional presentation of (constitutive presentation), a harmless foreign antigen and autoantigen (30-80% is a self-synthetic defective protein), induces and maintains peripheral tolerance by inducing regulatory T cell differentiation. DCs cells have two seemingly contradictory functions. It is through its judgment of the "self" and "non-self" antigens that it determines the different responses of the immune system and, at the appropriate time, produces an appropriate response or tolerance, thereby maintaining the immune homeostasis of the body; therefore, DCs cells are used to regulate and improve the immune response of therapeutic vaccines, upregulating or down-regulating specific immune responses. It has always been an important direction in the design of therapeutic vaccines. Although DCs cells have a strong ability to ingest antigens, However, the nonspecific way of uptake and presentation of antigens will result in the vaccine being unable to be effectively presented, thus affecting the subsequent effects of the vaccine. Using DCs to improve the immunogenicity of DCs, is an important vaccine design strategy. With the development of molecular immunology and DC cell biology, many molecules specifically expressed in DC have been identified. Recently discovered lectin receptors, which are restricted by DC, have become a new target pathway. DEC205 and DC-SIGN.DC-SIGN (DC-specific intracellular adhesion molecule-grabbing nonintegrin) receptors, for example, are lectin-like receptors found in 2002 that are restricted to DC and certain tissue macrophages. DC-SIGN has been shown to be not only a pathogen receptor, but also an important antigen receptor. Effective uptake of microamounts of HIV and CMV virus particles in mucosal tissue, followed by MHC-I molecules and MHC-II
【学位授予单位】：第三军医大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392
【参考文献】
相关期刊论文 前1条
1 黎万玲;王槐志;倪兵;姜曼;吴玉章;;磁转联合脂质体实现高效细胞转染[J];免疫学杂志;2005年06期
，本文编号：2276998
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