自身免疫調(diào)節(jié)因子（AIRE）作為轉(zhuǎn)錄因子主要表達(dá)在胸腺髓質(zhì)上皮細(xì)胞中,負(fù)責(zé)提呈不同組織特異性抗原進(jìn)而促進(jìn)T細(xì)胞的陰性選擇及其發(fā)育成熟。此外,AIRE也能夠促進(jìn)調(diào)節(jié)性T細(xì)胞的發(fā)育。AIRE基因突變可導(dǎo)致多器官的自身免疫病和皮膚粘膜念珠菌病,即APECED,該患者體內(nèi)通常會(huì)產(chǎn)生針對(duì)不同腺體組織,如睪丸、卵巢和甲狀腺等的自身抗體。AIRE基因也表達(dá)在胸腺外的不同部位,如次級(jí)淋巴器官、單核巨噬細(xì)胞中,誘導(dǎo)清除中樞耐受逃逸的自身反應(yīng)性T細(xì)胞。也有研究顯示AIRE也可用于治療移植物抗宿主病。一些研究發(fā)現(xiàn)胸腺外表達(dá)的AIRE可能通過(guò)調(diào)控PRR表達(dá)和抗原提呈細(xì)胞的MHC分子,在局部組織免疫應(yīng)答中發(fā)揮重要作用。AIRE缺陷患者更易感念珠菌病,而正常機(jī)體主要通過(guò)巨噬細(xì)胞和樹(shù)突狀細(xì)胞介導(dǎo)的固有免疫發(fā)揮抗念珠菌作用。因此為了探討AIRE對(duì)巨噬細(xì)胞應(yīng)答白色念珠菌中的作用,本研究主要通過(guò)白色念珠菌體外刺激AIRE敲除鼠腹腔巨噬細(xì)胞檢測(cè)M1相關(guān)分子及PRR表達(dá),以及建立白色念珠菌感染的AIRE敲除鼠模型進(jìn)一步研究,結(jié)果發(fā)現(xiàn):1.在體外,AIRE敲除鼠腹腔巨噬細(xì)胞在對(duì)白色念珠菌應(yīng)答時(shí),M1型巨噬細(xì)胞相關(guān)分子IL-6及... 

【文章來(lái)源】：吉林大學(xué)吉林省 211工程院校 985工程院校 教育部直屬院校

【文章頁(yè)數(shù)】：84 頁(yè)

【學(xué)位級(jí)別】：碩士

【文章目錄】：
提要
Preface
中文摘要
abstract
Abbreviations
1 Literature review
    1.1 AIRE as an important regulator for T cell development
        1.1.1 Mechanism of tolerance at thymus
        1.1.2 Molecular features of AIRE functioning
    1.2 AIRE ahead of auto antigens
    1.3 Anti-tumor immunity of AIRE
    1.4 TSA independent functions of AIRE
    1.5 Activity of AIRE in GVHD
    1.6 Extra thymic expression of AIRE and its role in peripheral tolerance
        1.6.1 AIREs tissue and cellular distributions
        1.6.2 AIRE's function in peripheral immune tolerance
    1.7 Immune Response to Candida albicans
        1.7.1 Antimicrobial proteins against Candida albicans
    1.8 Response of Macrophage to Candida albicans components
        1.8.1 Recognition ofβ-1,6-glucans of Candida albicans by Dectin-1 of macrophage
        1.8.2 Macrophages response to cell wall chitin
        1.8.3 Mannoprotiens interaction with macrophage
    1.9 Proinflammatory macrophages M1 and anti-inflammatory M2 and their response to Candida albicans
    1.10 Secretion of cytokines in the response of Candida albicans
    1.11 Candida albicans infections as a common consequences of APECED patients
2 Study design
3 Material and method
    3.1 Materials
        3.1.1 Mice
        3.1.2 Candida albicans strain
        3.1.3 Main reagents
        3.1.4 Main equipment
        3.1.5 Reagents preparation
    3.2 Methods
        3.2.1 Isolation and polarization of mice peritoneal macrophage
        3.2.2 Flow cytometry
        3.2.3 Establishment of systemic candidiasis model
        3.2.4 Macrophage and candida albicans co-culturing
        3.2.5 RNA isolation and RT-qPCR analysis
        3.2.6 Statistical Analysis
4 Results
    4.1 Effects of AIRE deficiency on macrophage response to Candida albicans in vitro.
        4.1.1 The culture of Candida albicans
        4.1.2 The macrophage isolation and identification from mice peritoneal cavity
        4.1.3 The stimulation of Candida albicans to macrophage
        4.1.4 Effects of AIRE on expression of M1 associated molecules in response to Candida albicans
        4.1.5 Effects of AIRE on PRR expression of macrophages in response to Candida albicans
    4.2 Effects of AIRE deficiency on the macrophage response to Candida albicans in vivo
        4.2.1 Observation of the general status of Candida albicans infected mice
        4.2.2 The effect of AIRE deficiency on the histological pathology in mice with Candida albicans infection
        4.2.3 The isolation and identification of peritoneal cavity macrophage from mice with Candida albicans infection
        4.2.4 The effect of AIRE deficiency on M1 related molecules expression in macrophage from Candida albicans infected mice
        4.2.5 The effect of AIRE deficiency on the survival of mice with Candida albicans infection
5 Discussion
6 Conclusion
References
Short introduction of the writer and attainment throughout research at school
Acknowledgement



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