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)細胞凋亡現(xiàn)象以后,人們認識到細胞死亡的形式有兩種:細胞壞死(necrosis)和細胞凋亡(apoptosis)。壞死是由細胞在遭受意外傷害后所導(dǎo)致的突發(fā)性死亡,故又稱作“事故性死亡”(accidental cell death)。凋亡是指在生理條件下或少數(shù)病理條件下(如病毒感染),由基因調(diào)控的細胞死亡。除了在細胞形態(tài)特征和生化特征這兩方面外,兩者最大的區(qū)別在于:壞死細胞激發(fā)炎癥反應(yīng),而凋亡細胞不激發(fā)炎癥反應(yīng)。隨著對凋亡細胞的深入研究,發(fā)現(xiàn)自細胞凋亡的早期開始,凋亡細胞膜表面發(fā)生的一系列分子水平的變化給吞噬細胞發(fā)出了足夠強烈的吞噬信號(eat me signal),使凋亡細胞能夠及時被周圍的吞噬細胞吞噬清除。研究表明如果凋亡細胞不能完全及時地被吞噬,則凋亡細胞會發(fā)生溶解破裂,從而釋放出胞內(nèi)容物,激發(fā)周圍組織的免疫炎癥反應(yīng),引起組織損傷;故把凋亡細胞膜溶解破裂激發(fā)免疫炎癥反應(yīng)稱作凋亡細胞的二步壞死。目前多數(shù)學(xué)者把凋亡細胞不激發(fā)炎癥反應(yīng)完全應(yīng)歸因于生理條件下凋亡細胞迅速被吞噬細胞吞噬清除,從而避免了凋亡細胞發(fā)生二步壞死,在此我們稱之為“被動吞噬理論”。通過對自身免疫性疾病的研究發(fā)現(xiàn),凋亡細胞是自身抗原的重要來源;而且發(fā)現(xiàn)吞噬細胞(特別是不成熟DC)吞噬凋亡細胞后,可以將凋亡細胞的抗原成分以MHCⅠ分子限制的方式遞呈給細胞毒細胞(CTL)。由此推測凋亡細胞被吞噬細胞吞噬后將完全可以激發(fā)出免疫炎癥反應(yīng),但事實并非如此,其原因何在?克隆選擇學(xué)說認為由于機體在胚胎時期已經(jīng)刪除了針對自身抗原的特異性克隆,從而對自身抗原產(chǎn)生天然的免疫耐受。克隆選擇學(xué)說的基礎(chǔ)是假設(shè)胚胎期和新生期動物的免疫細胞尚不成熟,不具備對抗原的反應(yīng)能力,此時當(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),胚胎期和新生期動物的免疫細
[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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