腺病毒介导HBsAg基因修饰的DC疫苗抗HBV免疫的实验研究

发布时间：2018-01-04 10:41

本文关键词：腺病毒介导HBsAg基因修饰的DC疫苗抗HBV免疫的实验研究　出处：《浙江大学》2005年博士论文　论文类型：学位论文

【摘要】：乙型肝炎病毒(Hepatitis B virus,HBV)是感染性肝病最常见的病原因子之一。有些人初次感染HBV后不能彻底清除病毒,成为慢性HBV携带者,从而形成肝硬化和肝细胞癌发病的高危人群。 CD8~+细胞毒性T细胞(Cytotoxic T Lymphocytes,CTLs)是急性肝炎患者机体清除HBV的一种重要防御成分。目前认为,病毒清除是由于CTL介导被HBV感染的肝细胞溶解和/或产生细胞因子(如IFN-γ等)的抗病毒效应,其中,多克隆、多特异性、应答强及IFN-γ分泌能力强的CTL尤为重要,而持续HBV感染者以弱而窄谱的特异性CD8~+T细胞应答为特征。因此,免疫治疗增强慢性感染者抗HBV的T细胞应答有望结束持续病毒感染。 HBV慢性感染的确切机制还不完全清楚,但与宿主T细胞应答不足或耐受相关。目前认识到,树突状细胞(Dendritic cells,DCs)是最有效的抗原提呈细胞(Antigen presenting cells,APCs),是诱导抗病毒免疫应答的中心环节。研究表明,慢性肝炎患者外周血单核细胞来源的DC细胞存在抗原提呈功能缺陷。 HBV转基因小鼠(Transgenic mice,Tg)是一种持续HBV感染模型,包含完整HBV基因组及表达其病毒基因产物,在肝细胞复制病毒,但肝脏无炎症表现,对HBV病毒抗原耐受,无特异性T细胞应答,是评价打破耐受和结束HBV持续感染的免疫治疗策略的良好实验模型。在HBVTg鼠中的研究发现,HBsAg蛋白或肽冲击的DC疫苗在诱导特异性CTL方面比重组HBsAg或质粒DNA疫
[Abstract]:Hepatitis B virus (HBV) is one of the most common causes of infectious liver disease. Some people can not completely eliminate the virus after first infection with HBV. Become chronic HBV carriers, thus forming cirrhosis and hepatocellular carcinoma high risk population. CD8 ~ cytotoxic T cells were cytotoxic T Lymphocytes. CTLs) is an important defensive component in the clearance of HBV in patients with acute hepatitis. Virus clearance is due to CTL mediated hepatocyte lysis and / or the production of cytokines (such as IFN- 纬, etc.) of the anti-viral effect, in which, polyclonal, multi-heterosexual. CTL with strong response and strong IFN- 纬 secretion is particularly important, and persistent HBV infection is characterized by weak and narrow spectrum specific CD8T cell response. Immunotherapy enhances T cell response to HBV in patients with chronic infection and is expected to end persistent viral infection. The exact mechanism of HBV chronic infection is not fully understood, but it is related to the host T cell response or tolerance. It is now recognized that dendritic cell / dendritic cell / dendritic cells. DCS is the most effective antigen-presenting cell, antigen presenting cells and APCs, which is the central link in inducing antiviral immune response. DC cells derived from peripheral blood monocytes in patients with chronic hepatitis have defective antigen presentation function. HBV transgenic mice are a persistent model of HBV infection, which contains the complete HBV genome and the expression of its viral gene products. The virus was duplicated in the hepatocytes, but there was no inflammation in the liver, no HBV antigen tolerance and no specific T cell response. It is a good experimental model to evaluate the immunotherapy strategy to break the tolerance and end the persistent infection of HBV. HBsAg protein or peptide pulsed DC vaccine is more effective than recombinant HBsAg or plasmid DNA in inducing specific CTL.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

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