本文關(guān)鍵詞：腺病毒介導(dǎo)HBsAg基因修飾的DC疫苗抗HBV免疫的實(shí)驗(yàn)研究　出處：《浙江大學(xué)》2005年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 肝炎病毒 乙型 樹突狀細(xì)胞 腺病毒 I型(Thl/Tcl)免疫應(yīng)答 細(xì)胞毒T淋巴細(xì)胞 DNA疫苗 轉(zhuǎn)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(xì)胞癌發(fā)病的高危人群。 CD8~+細(xì)胞毒性T細(xì)胞(Cytotoxic T Lymphocytes,CTLs)是急性肝炎患者機(jī)體清除HBV的一種重要防御成分。目前認(rèn)為,病毒清除是由于CTL介導(dǎo)被HBV感染的肝細(xì)胞溶解和/或產(chǎn)生細(xì)胞因子(如IFN-γ等)的抗病毒效應(yīng),其中,多克隆、多特異性、應(yīng)答強(qiáng)及IFN-γ分泌能力強(qiáng)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(xì)胞應(yīng)答為特征。因此,免疫治療增強(qiáng)慢性感染者抗HBV的T細(xì)胞應(yīng)答有望結(jié)束持續(xù)病毒感染。 HBV慢性感染的確切機(jī)制還不完全清楚,但與宿主T細(xì)胞應(yīng)答不足或耐受相關(guān)。目前認(rèn)識到,樹突狀細(xì)胞(Dendritic cells,DCs)是最有效的抗原提呈細(xì)胞(Antigen presenting cells,APCs),是誘導(dǎo)抗病毒免疫應(yīng)答的中心環(huán)節(jié)。研究表明,慢性肝炎患者外周血單核細(xì)胞來源的DC細(xì)胞存在抗原提呈功能缺陷。 HBV轉(zhuǎn)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(dá)其病毒基因產(chǎn)物,在肝細(xì)胞復(fù)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(xì)胞應(yīng)答,是評價(jià)打破耐受和結(jié)束HBV持續(xù)感染的免疫治療策略的良好實(shí)驗(yàn)?zāi)Ｐ�。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(dǎo)特異性CTL方面比重組HBsAg或質(zhì)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(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R392

【參考文獻(xiàn)】

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1 柯亨寧,斯崇文,成軍,于敏,劉丹,田秀蘭;HBsAg DNA疫苗誘導(dǎo)小鼠體液免疫及抑制轉(zhuǎn)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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