本文選題：凋亡 + 炎癥��； 參考：《浙江大學(xué)》2005年博士論文

【摘要】：引言 自從1972年Kerr等發(fā)現(xiàn)細(xì)胞凋亡現(xiàn)象以后,人們認(rèn)識(shí)到細(xì)胞死亡的形式有兩種:細(xì)胞壞死(necrosis)和細(xì)胞凋亡(apoptosis)。壞死是由細(xì)胞在遭受意外傷害后所導(dǎo)致的突發(fā)性死亡,故又稱(chēng)作“事故性死亡”(accidental cell death)。凋亡是指在生理?xiàng)l件下或少數(shù)病理?xiàng)l件下(如病毒感染),由基因調(diào)控的細(xì)胞死亡。除了在細(xì)胞形態(tài)特征和生化特征這兩方面外,兩者最大的區(qū)別在于:壞死細(xì)胞激發(fā)炎癥反應(yīng),而凋亡細(xì)胞不激發(fā)炎癥反應(yīng)。隨著對(duì)凋亡細(xì)胞的深入研究,發(fā)現(xiàn)自細(xì)胞凋亡的早期開(kāi)始,凋亡細(xì)胞膜表面發(fā)生的一系列分子水平的變化給吞噬細(xì)胞發(fā)出了足夠強(qiáng)烈的吞噬信號(hào)(eat me signal),使凋亡細(xì)胞能夠及時(shí)被周?chē)耐淌杉?xì)胞吞噬清除。研究表明如果凋亡細(xì)胞不能完全及時(shí)地被吞噬,則凋亡細(xì)胞會(huì)發(fā)生溶解破裂,從而釋放出胞內(nèi)容物,激發(fā)周?chē)M織的免疫炎癥反應(yīng),引起組織損傷;故把凋亡細(xì)胞膜溶解破裂激發(fā)免疫炎癥反應(yīng)稱(chēng)作凋亡細(xì)胞的二步壞死。目前多數(shù)學(xué)者把凋亡細(xì)胞不激發(fā)炎癥反應(yīng)完全應(yīng)歸因于生理?xiàng)l件下凋亡細(xì)胞迅速被吞噬細(xì)胞吞噬清除,從而避免了凋亡細(xì)胞發(fā)生二步壞死,在此我們稱(chēng)之為“被動(dòng)吞噬理論”。通過(guò)對(duì)自身免疫性疾病的研究發(fā)現(xiàn),凋亡細(xì)胞是自身抗原的重要來(lái)源;而且發(fā)現(xiàn)吞噬細(xì)胞(特別是不成熟DC)吞噬凋亡細(xì)胞后,可以將凋亡細(xì)胞的抗原成分以MHCⅠ分子限制的方式遞呈給細(xì)胞毒細(xì)胞(CTL)。由此推測(cè)凋亡細(xì)胞被吞噬細(xì)胞吞噬后將完全可以激發(fā)出免疫炎癥反應(yīng),但事實(shí)并非如此,其原因何在?克隆選擇學(xué)說(shuō)認(rèn)為由于機(jī)體在胚胎時(shí)期已經(jīng)刪除了針對(duì)自身抗原的特異性克隆,從而對(duì)自身抗原產(chǎn)生天然的免疫耐受�？寺∵x擇學(xué)說(shuō)的基礎(chǔ)是假設(shè)胚胎期和新生期動(dòng)物的免疫細(xì)胞尚不成熟,不具備對(duì)抗原的反應(yīng)能力,此時(shí)當(dāng)接受自身抗原的刺激后便導(dǎo)導(dǎo)致克隆刪除,從而形成耐受。但是新近研究發(fā)現(xiàn),胚胎期和新生期動(dòng)物的免疫細(xì)
[Abstract]:Introduction Since the discovery of apoptosis by Kerr in 1972, it has been recognized that there are two forms of cell death: necrosis and apoptosis. Necrosis is the sudden death of cells caused by accidental injury, so it is also called accidental cell death. Apoptosis is the death of genetically regulated cells under physiological conditions or a few pathological conditions (e.g. virus infection). In addition to the morphological and biochemical characteristics of the cells, the biggest difference between the two is that necrotic cells stimulate inflammation, while apoptotic cells do not. With the further study of apoptotic cells, it was found that the early stage of apoptosis began. A series of changes at molecular level on the surface of apoptotic cell membrane give phagocytic signal to phagocytic cell which is strong enough to make the apoptotic cell can be eliminated by phagocytosis around the phagocytes in time. Studies have shown that if the apoptotic cells can not be completely phagocytized in time, the apoptotic cells will be dissolved and ruptured, which will release the contents of the cells, stimulate the immune inflammatory reaction of the surrounding tissues, and cause tissue damage. Therefore, the dissolution and rupture of apoptotic cell membrane to stimulate immune inflammation is called two-step necrosis of apoptotic cells. At present, most scholars attribute the non-inflammatory response of apoptotic cells to the phagocytic phagocytosis and elimination of apoptotic cells under physiological conditions, thus avoiding two-step necrosis of apoptotic cells, which is called "passive phagocytosis theory". Through the study of autoimmune diseases, it was found that apoptotic cells were the important source of autoantigen, and that phagocytes, especially immature DCs, phagocytosis of apoptotic cells, The antigenic components of apoptotic cells can be presented to cytotoxic cells by MHC 鈪，

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