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  本文關鍵詞：腺病毒介導HBsAg基因修飾的DC疫苗抗HBV免疫的實驗研究　出處：《浙江大學》2005年博士論文　論文類型：學位論文

  更多相關文章： 肝炎病毒 乙型 樹突狀細胞 腺病毒 I型(Thl/Tcl)免疫應答 細胞毒T淋巴細胞 DNA疫苗 轉基因小鼠

【摘要】：乙型肝炎病毒(Hepatitis B virus,HBV)是感染性肝病最常見的病原因子之一。有些人初次感染HBV后不能徹底清除病毒,成為慢性HBV攜帶者,從而形成肝硬化和肝細胞癌發(fā)病的高危人群。 CD8~+細胞毒性T細胞(Cytotoxic T Lymphocytes,CTLs)是急性肝炎患者機體清除HBV的一種重要防御成分。目前認為,病毒清除是由于CTL介導被HBV感染的肝細胞溶解和/或產(chǎn)生細胞因子(如IFN-γ等)的抗病毒效應,其中,多克隆、多特異性、應答強及IFN-γ分泌能力強的CTL尤為重要,而持續(xù)HBV感染者以弱而窄譜的特異性CD8~+T細胞應答為特征。因此,免疫治療增強慢性感染者抗HBV的T細胞應答有望結束持續(xù)病毒感染。 HBV慢性感染的確切機制還不完全清楚,但與宿主T細胞應答不足或耐受相關。目前認識到,樹突狀細胞(Dendritic cells,DCs)是最有效的抗原提呈細胞(Antigen presenting cells,APCs),是誘導抗病毒免疫應答的中心環(huán)節(jié)。研究表明,慢性肝炎患者外周血單核細胞來源的DC細胞存在抗原提呈功能缺陷。 HBV轉基因小鼠(Transgenic mice,Tg)是一種持續(xù)HBV感染模型,包含完整HBV基因組及表達其病毒基因產(chǎn)物,在肝細胞復制病毒,但肝臟無炎癥表現(xiàn),對HBV病毒抗原耐受,無特異性T細胞應答,是評價打破耐受和結束HBV持續(xù)感染的免疫治療策略的良好實驗模型。在HBVTg鼠中的研究發(fā)現(xiàn),HBsAg蛋白或肽沖擊的DC疫苗在誘導特異性CTL方面比重組HBsAg或質粒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- 緯, etc.) of the anti-viral effect, in which, polyclonal, multi-heterosexual. CTL with strong response and strong IFN- 緯 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.
【學位授予單位】：浙江大學
【學位級別】：博士
【學位授予年份】：2005
【分類號】：R392

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相關期刊論文 前1條

1 柯亨寧,斯崇文,成軍,于敏,劉丹,田秀蘭;HBsAg DNA疫苗誘導小鼠體液免疫及抑制轉基因鼠表面抗原的產(chǎn)生[J];中華內(nèi)科雜志;2000年05期

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本文編號：1378126