本文選題：日本血吸蟲(chóng) + 蟲(chóng)卵肉芽腫　； 參考：《蘇州大學(xué)》2005年碩士論文

【摘要】：近年來(lái)研究表明,血吸蟲(chóng)卵肉芽腫病變主要是由蟲(chóng)卵可溶性抗原誘導(dǎo)的以Th2型免疫優(yōu)勢(shì)應(yīng)答介導(dǎo)的,以嗜酸性粒細(xì)胞等多種炎癥細(xì)胞浸潤(rùn)為主的免疫病理反應(yīng)�？刂蒲x(chóng)卵肉芽腫病變對(duì)防止晚期血吸蟲(chóng)病肝纖維化的發(fā)生發(fā)展具有重要作用。利用Th1和Th2亞群的相互拮抗作用來(lái)調(diào)節(jié)蟲(chóng)卵肉芽腫反應(yīng),可改善纖維化病變。含非甲基化CpG序列的寡脫氧核苷酸(免疫刺激序列),經(jīng)體外和大量的動(dòng)物實(shí)驗(yàn)證實(shí)它能激活哺乳動(dòng)物的天然免疫系統(tǒng),刺激巨噬細(xì)胞、單核細(xì)胞等產(chǎn)生IFN-γ、IL-12等細(xì)胞因子,激發(fā)強(qiáng)烈的Th1型免疫應(yīng)答反應(yīng),或調(diào)節(jié)免疫應(yīng)答向Th1型轉(zhuǎn)換,抑制Th2型免疫應(yīng)答。小鼠動(dòng)物實(shí)驗(yàn)表明CpG亦能夠調(diào)節(jié)曼氏血吸蟲(chóng)蟲(chóng)卵誘導(dǎo)的Th2型免疫應(yīng)答,減輕蟲(chóng)卵肉芽腫反應(yīng)。本研究通過(guò)觀察CpG在體內(nèi)、外對(duì)Th1/Th2免疫偏移的調(diào)控作用,探討其對(duì)日本血吸蟲(chóng)卵肉芽腫及纖維化發(fā)生、發(fā)展的影響。結(jié)果表明:在體外實(shí)驗(yàn)中,CpG可協(xié)同SEA或ConA顯著上調(diào)體外培養(yǎng)小鼠脾淋巴細(xì)胞Th1型細(xì)胞因子IFN-γ的表達(dá)水平,下調(diào)Th2型細(xì)胞因子IL-4的表達(dá)水平,特別是促進(jìn)IFN-γ的表達(dá)作用強(qiáng)烈,并結(jié)合Th2分化指數(shù)進(jìn)一步說(shuō)明CpG主要介導(dǎo)Th1型免疫應(yīng)答;在體內(nèi)實(shí)驗(yàn)中,CpG免疫鼠產(chǎn)生肝臟蟲(chóng)卵肉芽腫的密度與生理鹽水對(duì)照組相比較低,單卵肉芽腫形成的肉芽腫體積與生理鹽水對(duì)照組有較明顯差異。血清抗體IgG及抗體亞類(lèi)IgG_1、IgG_(2a)檢測(cè)表明:6、8w時(shí)CpG組血清抗體IgG較N-CpG組以及NS對(duì)照組水平低,6w時(shí)CpG組IgG_(2a)/IgG_1的比值較對(duì)照組高,提示CpG主要誘導(dǎo)Th1型免疫應(yīng)答。本研究表明CpG作為一個(gè)新型的免疫調(diào)節(jié)劑及其作為潛在的疫苗佐劑具有重要的理論和應(yīng)用價(jià)值,研究結(jié)果為探索控制日本血吸蟲(chóng)蟲(chóng)卵肉芽腫病變的新途徑提供了實(shí)驗(yàn)依據(jù)。
[Abstract]:Recent studies have shown that schistosomiasis oocyte granulomatosis is mainly induced by egg soluble antigen mediated by Th2 immune dominant response and mainly by eosinophilic granulocyte infiltration. The control of schistosomiasis oocyte granuloma plays an important role in preventing the occurrence and development of liver fibrosis in advanced schistosomiasis. Using the antagonism of Th1 and Th2 subsets to regulate the egg granuloma reaction can improve the fibrosis lesion. Oligodeoxynucleotides (oligodeoxynucleotides) containing non-methylated CpG sequences (immunostimulatory sequences) have been shown to activate mammalian innate immune system, stimulate macrophages and monocytes to produce cytokines such as IFN- 緯 IL-12. To stimulate a strong Th1 type immune response, or to regulate the transition from immune response to Th1 type, and to inhibit Th2 type immune response. Animal experiments in mice showed that CpG could also modulate the Th2 type immune response induced by Schistosoma mansoni eggs and alleviate the egg granuloma response. The aim of this study was to investigate the effects of CpG on the development and development of schistosomiasis japonicum oocyte granuloma and fibrosis by observing the effect of CpG on Th1/Th2 immune shift in vivo and in vitro. The results showed that CpG could significantly upregulate the expression of Th1 type cytokine IFN- 緯 and down-regulate the expression of Th2 type cytokine IL-4, especially the expression of IFN- 緯, in combination with SEA or ConA. Combined with the differentiation index of Th2, CpG mainly mediated the Th1 type immune response, and the density of liver egg granuloma in CpG immunized mice was lower than that in normal saline control group. The volume of granuloma formed by single egg granuloma was significantly different from that of normal saline control group. The detection of serum antibody IgG and antibody subclass IgG tip2a showed that the ratio of serum antibody IgG in CpG group was higher than that in N-CpG group and CpG group at 6w / 6w, suggesting that CpG mainly induces Th1 type immune response. This study shows that CpG as a new immunomodulator and as a potential vaccine adjuvant has important theoretical and practical value. The results provide experimental basis for exploring a new approach to control schistosome egg granuloma in Schistosoma japonicum.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類(lèi)號(hào)】：R392

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