早期凋亡细胞炎症及免疫抑制性质的实验研究

发布时间：2018-04-22 19:39

  本文选题：凋亡 + 炎症　； 参考：《浙江大学》2005年博士论文

【摘要】：引言 自从1972年Kerr等发现细胞凋亡现象以后,人们认识到细胞死亡的形式有两种:细胞坏死(necrosis)和细胞凋亡(apoptosis)。坏死是由细胞在遭受意外伤害后所导致的突发性死亡,故又称作“事故性死亡”(accidental cell death)。凋亡是指在生理条件下或少数病理条件下(如病毒感染),由基因调控的细胞死亡。除了在细胞形态特征和生化特征这两方面外,两者最大的区别在于:坏死细胞激发炎症反应,而凋亡细胞不激发炎症反应。随着对凋亡细胞的深入研究,发现自细胞凋亡的早期开始,凋亡细胞膜表面发生的一系列分子水平的变化给吞噬细胞发出了足够强烈的吞噬信号(eat me signal),使凋亡细胞能够及时被周围的吞噬细胞吞噬清除。研究表明如果凋亡细胞不能完全及时地被吞噬,则凋亡细胞会发生溶解破裂,从而释放出胞内容物,激发周围组织的免疫炎症反应,引起组织损伤;故把凋亡细胞膜溶解破裂激发免疫炎症反应称作凋亡细胞的二步坏死。目前多数学者把凋亡细胞不激发炎症反应完全应归因于生理条件下凋亡细胞迅速被吞噬细胞吞噬清除,从而避免了凋亡细胞发生二步坏死,在此我们称之为“被动吞噬理论”。通过对自身免疫性疾病的研究发现,凋亡细胞是自身抗原的重要来源;而且发现吞噬细胞(特别是不成熟DC)吞噬凋亡细胞后,可以将凋亡细胞的抗原成分以MHCⅠ分子限制的方式递呈给细胞毒细胞(CTL)。由此推测凋亡细胞被吞噬细胞吞噬后将完全可以激发出免疫炎症反应,但事实并非如此,其原因何在?克隆选择学说认为由于机体在胚胎时期已经删除了针对自身抗原的特异性克隆,从而对自身抗原产生天然的免疫耐受。克隆选择学说的基础是假设胚胎期和新生期动物的免疫细胞尚不成熟,不具备对抗原的反应能力,此时当接受自身抗原的刺激后便导导致克隆删除,从而形成耐受。但是新近研究发现,胚胎期和新生期动物的免疫细
[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，

本文编号：1788621