嚴重創(chuàng)傷對細胞免疫和樹突狀細胞的影響及其意義
發(fā)布時間：2019-01-05 20:39
【摘要】： 創(chuàng)傷是嚴重威脅人類生命健康的原因之一。近年來據(jù)我國衛(wèi)生部統(tǒng)計,損傷和中毒已經(jīng)成為我國第五大死亡原因。而在發(fā)達國家創(chuàng)傷是所有人群的第三大死亡原因,也是導(dǎo)致40歲以下人群死亡的主要原因。創(chuàng)傷后往往出現(xiàn)感染、膿毒癥、全身炎癥反應(yīng)甚至多器官功能障礙綜合征,使創(chuàng)傷的救治變得異常困難。而這些現(xiàn)象與創(chuàng)傷后免疫系統(tǒng)的變化有重要關(guān)系。很多研究都指出創(chuàng)傷能引起機體免疫系統(tǒng)產(chǎn)生復(fù)雜的變化,一方面炎性因子如IL-6等明顯升高,往往造成過度炎癥;另一方面抗原提呈功能下降,又導(dǎo)致T、B細胞反應(yīng)性下降,免疫功能受到明顯抑制,往往導(dǎo)致嚴重感染,從而這兩方面共同造成了嚴重創(chuàng)傷的高死亡率。只有及時糾正失去平衡的免疫系統(tǒng),恢復(fù)正常的先天性及適應(yīng)性免疫應(yīng)答才能切實提高嚴重創(chuàng)傷的存活率。 而樹突狀細胞(DC)是聯(lián)系先天性免疫和適應(yīng)性免疫的橋梁,作為專職的抗原提呈細胞(APC),DC在啟動和調(diào)節(jié)先天性及適應(yīng)性免疫應(yīng)答中具有關(guān)鍵性的作用。機體內(nèi)有兩種DC:用于攝取抗原的未成熟DC和用于刺激免疫細胞的成熟DC。未成熟DC分布于血液和全身組織中,它們提取并俘獲抗原,構(gòu)筑了最基本的防御網(wǎng)絡(luò)。一旦攝取了抗原,DC就向淋巴器官遷移,同時變?yōu)槌墒霥C,將這些抗原呈遞給免疫細胞,刺激未致敏的T細胞增殖并分化為效應(yīng)T細胞。在這個過程中,DC表現(xiàn)出不同的表面抗原分子和功能。如果該過程受到干擾,那么整個免疫系統(tǒng)的功能也會受到影響。因此研究創(chuàng)傷后DC的生物學(xué)特征,如數(shù)量,種類,表型及其功能是否發(fā)生變化具有重要意義。 然而到目前為止,關(guān)于創(chuàng)傷對免疫系統(tǒng)的影響,大多研究創(chuàng)傷后T、B細胞功能的變化。至于創(chuàng)傷對DC的影響卻研究甚少,這方面的研究現(xiàn)狀主要是:(1)創(chuàng)傷后單核細胞的分化異常,來自創(chuàng)傷病人的混合淋巴細胞反應(yīng)低下的單核細胞在體外用粒-巨噬細胞集落刺激因子(GM-CSF)和白細胞介素(IL)-4誘導(dǎo)下,不能分化為未成熟DC;(2)在急性興奮性損害所致的腦損傷實驗中,發(fā)現(xiàn)有DC遷移到腦并在腦中聚集,而正常的中樞神經(jīng)系統(tǒng)實質(zhì)區(qū)是沒有DC存在的,這暗示DC參與了神經(jīng)損傷的病理過程;(3)脊髓損傷病人的單核細胞在體外誘導(dǎo)分化為DC時不能發(fā)育為成熟DC,用抗原預(yù)處理的巨噬細胞和DC可以促進脊髓損傷動物模型的神經(jīng)修復(fù),接種用髓磷脂堿蛋白多肽刺激的DC也可以促進脊髓損傷后的神經(jīng)功能恢復(fù)。 綜上所述,可以看出以上研究均沒有涉及到創(chuàng)傷對自身DC的直接影響,因此本課題主要以創(chuàng)傷后的動物為研究對象,研究創(chuàng)傷后DC生物學(xué)功能的變化及其
[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.
【學(xué)位授予單位】：重慶大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R641;R392
本文編號：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.
【學(xué)位授予單位】：重慶大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R641;R392
【參考文獻】
相關(guān)期刊論文 前1條
1 王正國;發(fā)達社會疾病——創(chuàng)傷[J];中華外科雜志;2004年01期
，本文編號：2402282
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