【摘要】：免疫自穩(wěn)是免疫應(yīng)答的最重要的特征之一,它保證了免疫應(yīng)答的自限性,即當(dāng)外來(lái)病原體或者抗原被機(jī)體清除后,免疫應(yīng)答會(huì)逐漸減弱直至恢復(fù)至免疫系統(tǒng)的靜息狀態(tài),以維持機(jī)體的相對(duì)的平衡,這提示機(jī)體必然存在相應(yīng)的正負(fù)反饋調(diào)節(jié)機(jī)制來(lái)實(shí)現(xiàn)這一功能。 在免疫應(yīng)答過(guò)程中,抗原遞呈細(xì)胞發(fā)揮著橋梁的作用,連接著外來(lái)的抗原的識(shí)別和相應(yīng)的效應(yīng)細(xì)胞的應(yīng)答。而樹(shù)突狀細(xì)胞(Dendritic cells,DC)是目前已知的功能最強(qiáng)的專職抗原遞呈細(xì)胞,具有直接刺激初始T細(xì)胞增殖的獨(dú)特功能。它們主要以非成熟狀態(tài)存在于非淋巴組織內(nèi),此時(shí),獲取抗原是其主要功能。當(dāng)外界的病原微生物或其它異物侵入機(jī)體,DC獲取抗原,遷移至外周免疫器官中,在此過(guò)程中,DC獲得成熟,主要表現(xiàn)為抗原攝取能力降低,而抗原遞呈功能增強(qiáng)。在外周免疫器官中,DC將抗原遞呈給T細(xì)胞,從而激發(fā)免疫應(yīng)答。根據(jù)機(jī)體的免疫自穩(wěn)的原則,DC不可能持續(xù)地活化T細(xì)胞,那么,完成了抗原遞呈功能的DC,其最終命運(yùn)是怎樣的呢?目前的研究表明,DC在活化T細(xì)胞的同時(shí),亦受到來(lái)自于T細(xì)胞的作用,引起自身的凋亡,以有效地下調(diào)免疫應(yīng)答。目前普遍認(rèn)為,成熟DC在完成抗原提呈功能而激活T細(xì)胞之后,通過(guò)自身發(fā)生凋亡而實(shí)現(xiàn)免疫負(fù)向調(diào)控。 但是,由于免疫應(yīng)答都是在外周免疫器官的微環(huán)境中進(jìn)行的,而免疫微環(huán)境由基質(zhì)細(xì)胞和細(xì)胞外基質(zhì)組成,含有眾多的膜分子和可溶性的細(xì)胞因子,因此,外周免疫器官特殊的微環(huán)境在為免疫應(yīng)答的進(jìn)行提供良好條件的同時(shí),也必將對(duì)參與免疫應(yīng)答的細(xì)胞的功能狀態(tài)和命運(yùn)有所調(diào)節(jié)。因此,脫離基質(zhì)微環(huán)境的影響而研究和談?wù)撁庖呒?xì)胞在應(yīng)答后的命運(yùn)歸宿,所得到的結(jié)論不可能反映在體的真實(shí)情況。有實(shí)驗(yàn)證實(shí),在不需要外來(lái)細(xì)胞因子的作用下,脾臟基質(zhì)長(zhǎng)期培養(yǎng)體系(LTC)中,可誘導(dǎo)造血前體細(xì)胞產(chǎn)生DC樣細(xì)胞,具有DC的形態(tài)和功能。也有研究發(fā)現(xiàn),肺部、腦組織和腎臟內(nèi)的DC在微環(huán)境的作用下,其功能發(fā)生變化,成為具有調(diào)節(jié)性作用的DC,我們以前的實(shí)驗(yàn)也證明,用來(lái)源于脾臟的內(nèi)皮型基質(zhì)細(xì)胞ESSC來(lái)模擬免疫微環(huán)境,將成熟DC與其共培養(yǎng)后,成熟DC獲得了繼續(xù)增殖的能力,而且,其功能也發(fā)生了質(zhì)的變化,由原來(lái)的刺激T細(xì)胞增殖變成只能誘導(dǎo)T細(xì)胞活化而不能刺激其增殖,而且可以抑制成熟DC誘導(dǎo)的T細(xì)胞的增殖。這提示免疫微環(huán)境對(duì)于DC的分化發(fā)育和功能具有很強(qiáng)的調(diào)節(jié)功能。 細(xì)胞凋亡是細(xì)胞維持機(jī)體內(nèi)環(huán)境穩(wěn)定的機(jī)制之一,一旦細(xì)胞凋亡發(fā)生異常,機(jī)體將發(fā)生腫瘤、自身免疫性疾病等等。也有實(shí)驗(yàn)證明,不同器官的微環(huán)境或者通過(guò)基質(zhì)細(xì)胞表面的分子或者通過(guò)分泌的可溶性因子,有助于不同類型的細(xì)胞免于凋亡(其實(shí),實(shí)驗(yàn)中僅僅是觀察對(duì)于細(xì)胞凋亡的預(yù)防作用)。比如,胸腺的上皮細(xì)胞可以抑制皮質(zhì)激索引起的胸腺細(xì)胞
[Abstract]:Immune self-stabilization is one of the most important characteristics of immune response, which ensures the self-limitation of immune response, that is, when foreign pathogens or antigens are removed by the body, the immune response will gradually weaken until the resting state of the immune system, in order to maintain the relative balance of the body, suggesting that the body must have corresponding positive and negative feedback regulation. Node mechanism to achieve this function.
In the process of immune response, antigen presenting cells act as a bridge between the recognition of foreign antigens and the response of corresponding effector cells. Immature state exists in non-lymphoid tissues, at this time, antigen acquisition is its main function. When external pathogenic microorganisms or other foreign bodies invade the body, DC acquires antigens and migrates to peripheral immune organs. During this process, DC matures, mainly manifested by decreased antigen uptake and enhanced antigen presenting function. According to the principle of immune self-stabilization, DC can not activate T cells continuously. What is the ultimate fate of DC which has completed the function of antigen presenting? Current studies have shown that DC is activated by T cells as well as T cells, causing itself. At present, it is generally believed that mature DCs activate T cells after completing antigen presenting function and achieve negative immune regulation through their own apoptosis.
However, because the immune response is carried out in the microenvironment of the peripheral immune organs, and the immune microenvironment is composed of stromal cells and extracellular matrix, containing a large number of membrane molecules and soluble cytokines, the special microenvironment of the peripheral immune organs will provide good conditions for the development of the immune response at the same time. The functional status and fate of the cells involved in the immune response are regulated. Therefore, the fate of the immune cells after the response can not be reflected in the conclusions drawn from the study and discussion of the fate of the immune cells without the influence of matrix microenvironment. Experiments have confirmed that the splenic matrix is cultured for a long time without the use of foreign cytokines. In LTC system, DC-like cells can be induced from hematopoietic progenitor cells, which have the morphology and function of DC. It has also been found that the function of DC in lung, brain and kidney changes under the action of microenvironment and becomes a DC with regulatory effect. Our previous experiments have also proved that ESSC, an endothelial stromal cell derived from the spleen, can be used as a DC. After co-culture with mature DCs in simulated immune microenvironment, mature DCs acquired the ability to continue to proliferate, and their functions changed from stimulating T cell proliferation to inducing T cell activation but not proliferation, and inhibiting T cell proliferation induced by mature DCs. It has a strong regulatory function in differentiation, development and function of DC.
Cell apoptosis is one of the mechanisms by which cells maintain homeostasis. Once abnormal apoptosis occurs, the body will develop tumors, autoimmune diseases and so on. For example, thymic epithelial cells inhibit cortex-activated index thymocytes
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R392

【共引文獻(xiàn)】

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4 李牧,尤勝國(guó),葛薇,馬雙,馬楠,趙春華;Induction of T-cell immunity against leukemia by dendritic cells pulsed with total RNA isolated from leukemia cells[J];Chinese Medical Journal;2003年11期

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本文編號(hào)：2213301