【摘要】：補(bǔ)體系統(tǒng)是天然免疫的重要組成部分,由30余種可溶性蛋白和膜結(jié)合蛋白組成,具有調(diào)理和溶解微生物、趨化和過(guò)敏毒素、清除免疫復(fù)合物等生物學(xué)功能。補(bǔ)體成分3(complement component 3,C3)是補(bǔ)體系統(tǒng)的中樞,補(bǔ)體激活的3條途徑即經(jīng)典途徑、旁路途徑和凝集素途徑都要通過(guò)激活C3才得以實(shí)現(xiàn)。C3可能是補(bǔ)體系統(tǒng)中功能最多的分子,它能與20余種蛋白質(zhì)相互作用,產(chǎn)生多種功能。近年來(lái)在C3基因敲除(C34~(-/-))小鼠的研究提示,C3可以觸發(fā)和調(diào)節(jié)獲得性免疫,形成了天然免疫和獲得性免疫之間的橋梁。然而,C3在細(xì)胞免疫或DTH反應(yīng)中的作用究竟如何,作用有多大,還不很清楚。 甘露聚糖結(jié)合凝集素(mannan-binding lectin,MBL)系C型凝集素超級(jí)家族中膠凝素家族成員,是天然免疫系統(tǒng)中的關(guān)鍵分子。它可選擇性識(shí)別多種病原體表面的糖結(jié)構(gòu),以不依賴(lài)抗體和C1q的方式激活補(bǔ)體系統(tǒng),發(fā)揮溶破和間接調(diào)理功能,還能與吞噬細(xì)胞表面膠凝素受體結(jié)合而起直接調(diào)理作用。但是,在調(diào)理吞噬中,補(bǔ)體系統(tǒng)的作用、MBL的直接調(diào)理作用究竟有多大?目前尚無(wú)明確的結(jié)論。 因此,本研究用卵白蛋白(ovalbumin,OVA)在C3基因敲除小鼠及野生型小鼠誘導(dǎo)足墊的DTH反應(yīng),探索C3在DTH中的可能作用;分別用C3~(-/-)小鼠和C3~(+/+)小鼠的血清處理各種病原體,并用抗MBL多克隆抗體處理血清,探索C3和MBL對(duì)巨噬細(xì)胞體外吞噬功能的影響。 一、目的 1.在C3~(-/-)和C3~(+/+)小鼠(C57BL/6)誘導(dǎo)DTH,探索C3在DTH中的作用。 2.研究MBL體外結(jié)合微生物的能力,探索C3和MBL對(duì)巨噬細(xì)胞吞噬功能的影響。
[Abstract]:Complement system is an important part of innate immunity. It is composed of more than 30 kinds of soluble proteins and membrane binding proteins. It has the biological functions of regulating and dissolving microorganisms chemotaxis and allergy toxins clearing immune complexes and so on. Complement component 3 (C 3) is the center of the complement system. The three pathways of complement activation are classical pathways. Both the bypass pathway and lectin pathway can be realized by activating C3. C3 may be the most functional molecule in the complement system. It can interact with more than 20 proteins and produce many functions. In recent years, studies in C34- / (- / -) mice have suggested that C3 can trigger and regulate acquired immunity and form a bridge between innate immunity and acquired immunity. However, the role and extent of C 3 in cellular immunity or DTH response is unclear. Mannan binding lectin (mannan-binding), a member of the C type lectin superfamily, is a key molecule in the innate immune system. It can selectively recognize the sugar structure on the surface of many pathogens, activate the complement system in a manner independent of antibodies and C1q, play the functions of dissolution and indirect conditioning, and play a direct role in regulating the surface of phagocytes by binding to the gelatin receptor. However, in conditioning and phagocytosis, the role of complement system in the direct conditioning of MBL is how much? There is no clear conclusion. Therefore, ovalbumin OVA was used to induce the DTH response of foot pad in C3 knockout mice and wild-type mice, to explore the possible role of C3 in DTH, and to treat various pathogens with the serum of C3- /-and C3- / mice, respectively. To explore the effect of C3 and MBL on phagocytosis of macrophages in vitro. First, objective 1. DTHs were induced in C3- /-and C3- / mice (C57BL/6) to explore the role of C3 in DTH. 2. To explore the effect of C3 and MBL on phagocytosis of macrophages by studying the ability of MBL to bind microorganism in vitro.
【學(xué)位授予單位】：第一軍醫(yī)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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