严重创伤对细胞免疫和树突状细胞的影响及其意义
发布时间：2019-01-05 20:39
【摘要】： 创伤是严重威胁人类生命健康的原因之一。近年来据我国卫生部统计,损伤和中毒已经成为我国第五大死亡原因。而在发达国家创伤是所有人群的第三大死亡原因,也是导致40岁以下人群死亡的主要原因。创伤后往往出现感染、脓毒症、全身炎症反应甚至多器官功能障碍综合征,使创伤的救治变得异常困难。而这些现象与创伤后免疫系统的变化有重要关系。很多研究都指出创伤能引起机体免疫系统产生复杂的变化,一方面炎性因子如IL-6等明显升高,往往造成过度炎症;另一方面抗原提呈功能下降,又导致T、B细胞反应性下降,免疫功能受到明显抑制,往往导致严重感染,从而这两方面共同造成了严重创伤的高死亡率。只有及时纠正失去平衡的免疫系统,恢复正常的先天性及适应性免疫应答才能切实提高严重创伤的存活率。 而树突状细胞(DC)是联系先天性免疫和适应性免疫的桥梁,作为专职的抗原提呈细胞(APC),DC在启动和调节先天性及适应性免疫应答中具有关键性的作用。机体内有两种DC:用于摄取抗原的未成熟DC和用于刺激免疫细胞的成熟DC。未成熟DC分布于血液和全身组织中,它们提取并俘获抗原,构筑了最基本的防御网络。一旦摄取了抗原,DC就向淋巴器官迁移,同时变为成熟DC,将这些抗原呈递给免疫细胞,刺激未致敏的T细胞增殖并分化为效应T细胞。在这个过程中,DC表现出不同的表面抗原分子和功能。如果该过程受到干扰,那么整个免疫系统的功能也会受到影响。因此研究创伤后DC的生物学特征,如数量,种类,表型及其功能是否发生变化具有重要意义。 然而到目前为止,关于创伤对免疫系统的影响,大多研究创伤后T、B细胞功能的变化。至于创伤对DC的影响却研究甚少,这方面的研究现状主要是:(1)创伤后单核细胞的分化异常,来自创伤病人的混合淋巴细胞反应低下的单核细胞在体外用粒-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素(IL)-4诱导下,不能分化为未成熟DC;(2)在急性兴奋性损害所致的脑损伤实验中,发现有DC迁移到脑并在脑中聚集,而正常的中枢神经系统实质区是没有DC存在的,这暗示DC参与了神经损伤的病理过程;(3)脊髓损伤病人的单核细胞在体外诱导分化为DC时不能发育为成熟DC,用抗原预处理的巨噬细胞和DC可以促进脊髓损伤动物模型的神经修复,接种用髓磷脂碱蛋白多肽刺激的DC也可以促进脊髓损伤后的神经功能恢复。 综上所述,可以看出以上研究均没有涉及到创伤对自身DC的直接影响,因此本课题主要以创伤后的动物为研究对象,研究创伤后DC生物学功能的变化及其
[Abstract]:Trauma is one of the serious threats to human life and health. According to the statistics of Ministry of Health in recent years, injury and poisoning have become the fifth leading cause of death in China. Trauma is the third leading cause of death in developed countries and the leading cause of death among people under 40. Infection, sepsis, systemic inflammation and multiple organ dysfunction syndrome often occur after trauma, which makes the treatment of trauma extremely difficult. These phenomena are associated with changes in the immune system after trauma. Many studies have pointed out that trauma can cause complex changes in the body's immune system. On the one hand, inflammatory factors such as IL-6 are obviously increased, which often cause excessive inflammation. On the other hand, the antigen-presenting function decreased, which led to the decrease of TnB cell reactivity and the obvious inhibition of immune function, which often led to severe infection, which together resulted in a high mortality rate of severe trauma. Only by correcting the unbalanced immune system and restoring the normal innate and adaptive immune response can the survival rate of severe trauma be improved. Dendritic cell (DC) is a bridge between innate immunity and adaptive immunity. As a specialized antigen presenting cell (APC), DC plays a key role in initiating and regulating innate and adaptive immune responses. There are two types of DC: in the body, immature DC for antigen uptake and mature DC. for stimulating immune cells. Immature DC are distributed in blood and whole body tissues. They extract and capture antigens and construct the most basic defense network. Once the antigens were ingested, DC migrated to the lymphoid organs and became mature DC, to present these antigens to the immune cells, which stimulated the proliferation and differentiation of unsensitized T cells into effector T cells. In this process, DC exhibits different surface antigen molecules and functions. If the process is disturbed, the function of the entire immune system will also be affected. Therefore, it is of great significance to study the biological characteristics, such as number, species, phenotype and function of DC after trauma. So far, however, the effects of trauma on the immune system have been largely studied. However, the effects of trauma on DC are seldom studied. The current research status is as follows: (1) abnormal differentiation of monocytes after trauma. Monocytes with low lymphocyte response from trauma patients could not differentiate into immature DC; induced by granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL) 4 in vitro. (2) in the experiment of brain injury caused by acute excitatory injury, it was found that DC migrated to the brain and gathered in the brain, while no DC existed in the normal central nervous system parenchyma, which suggested that DC was involved in the pathological process of nerve injury. (3) the monocytes of spinal cord injury patients could not develop into mature DC, macrophages and DC pretreated with antigen when they differentiated into DC in vitro, which could promote the nerve repair of spinal cord injury animal model. DC stimulated by myelin peptide could also promote the recovery of neural function after spinal cord injury. To sum up, we can see that all the above studies did not involve the direct effects of trauma on their own DC. Therefore, this study mainly focused on the post-traumatic animals as the research object, to study the changes of DC biological function after trauma and the changes of DC biological function.
【学位授予单位】：重庆大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R641;R392
本文编号：2402282
[Abstract]:Trauma is one of the serious threats to human life and health. According to the statistics of Ministry of Health in recent years, injury and poisoning have become the fifth leading cause of death in China. Trauma is the third leading cause of death in developed countries and the leading cause of death among people under 40. Infection, sepsis, systemic inflammation and multiple organ dysfunction syndrome often occur after trauma, which makes the treatment of trauma extremely difficult. These phenomena are associated with changes in the immune system after trauma. Many studies have pointed out that trauma can cause complex changes in the body's immune system. On the one hand, inflammatory factors such as IL-6 are obviously increased, which often cause excessive inflammation. On the other hand, the antigen-presenting function decreased, which led to the decrease of TnB cell reactivity and the obvious inhibition of immune function, which often led to severe infection, which together resulted in a high mortality rate of severe trauma. Only by correcting the unbalanced immune system and restoring the normal innate and adaptive immune response can the survival rate of severe trauma be improved. Dendritic cell (DC) is a bridge between innate immunity and adaptive immunity. As a specialized antigen presenting cell (APC), DC plays a key role in initiating and regulating innate and adaptive immune responses. There are two types of DC: in the body, immature DC for antigen uptake and mature DC. for stimulating immune cells. Immature DC are distributed in blood and whole body tissues. They extract and capture antigens and construct the most basic defense network. Once the antigens were ingested, DC migrated to the lymphoid organs and became mature DC, to present these antigens to the immune cells, which stimulated the proliferation and differentiation of unsensitized T cells into effector T cells. In this process, DC exhibits different surface antigen molecules and functions. If the process is disturbed, the function of the entire immune system will also be affected. Therefore, it is of great significance to study the biological characteristics, such as number, species, phenotype and function of DC after trauma. So far, however, the effects of trauma on the immune system have been largely studied. However, the effects of trauma on DC are seldom studied. The current research status is as follows: (1) abnormal differentiation of monocytes after trauma. Monocytes with low lymphocyte response from trauma patients could not differentiate into immature DC; induced by granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL) 4 in vitro. (2) in the experiment of brain injury caused by acute excitatory injury, it was found that DC migrated to the brain and gathered in the brain, while no DC existed in the normal central nervous system parenchyma, which suggested that DC was involved in the pathological process of nerve injury. (3) the monocytes of spinal cord injury patients could not develop into mature DC, macrophages and DC pretreated with antigen when they differentiated into DC in vitro, which could promote the nerve repair of spinal cord injury animal model. DC stimulated by myelin peptide could also promote the recovery of neural function after spinal cord injury. To sum up, we can see that all the above studies did not involve the direct effects of trauma on their own DC. Therefore, this study mainly focused on the post-traumatic animals as the research object, to study the changes of DC biological function after trauma and the changes of DC biological function.
【学位授予单位】：重庆大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R641;R392
【参考文献】
相关期刊论文 前1条
1 王正国;发达社会疾病——创伤[J];中华外科杂志;2004年01期
，本文编号：2402282
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