日本血吸蟲感染對Th17細(xì)胞應(yīng)答影響的研究
發(fā)布時(shí)間：2019-06-13 23:01
【摘要】：未致敏(na(l|¨)ve)CD~(4+)T細(xì)胞在外周淋巴組織中經(jīng)病原體抗原刺激后,可分化成Th1和Th2兩大類CD~(4+)效應(yīng)T細(xì)胞。Th1細(xì)胞主要分泌IL-2、IFN-γ和TNF-β等細(xì)胞因子,調(diào)節(jié)細(xì)胞免疫;而Th2細(xì)胞主要分泌IL-4、IL-5、IL-6、IL-10及IL-13等細(xì)胞因子,調(diào)節(jié)體液免疫。同時(shí),二者相互抑制、相互調(diào)節(jié),協(xié)調(diào)參與維持機(jī)體的正常免疫功能。近年來,在一些自身免疫病和過敏原特異性反應(yīng)研究中發(fā)現(xiàn)一種產(chǎn)生白介素17((interleukin17;IL--17))的特殊CD~(4+)T細(xì)胞。該型CD~(4+)T細(xì)胞同傳統(tǒng)Th1和Th2細(xì)胞具有明顯不同的特征。雖然其功能還沒有被完全闡明,但越來越多的證據(jù)表明Th17細(xì)胞在宿主防御一些特定的胞外病原體、如不能被Th1類和Th2類有效清除的病原體起重要的保護(hù)作用。CD~(4+)T細(xì)胞除了分化為Th1、Th2和Th17這三大類效應(yīng)細(xì)胞之外,還可以分化為一群CD~(4+)CD25+調(diào)節(jié)性T(Tregulatorycell,Treg)細(xì)胞,它主要通過細(xì)胞與細(xì)胞之間的直接接觸和/或分泌一些抑制性細(xì)胞因子,如TGF-β和IL-10等發(fā)揮免疫負(fù)調(diào)控的作用;總之這些細(xì)胞亞群在清除感染、免疫病理損害中發(fā)揮著重要的作用。 與Th1和Th2細(xì)胞相似,Th17細(xì)胞的分化也需要特定的細(xì)胞因子和轉(zhuǎn)錄因子。TGF-β與IL--6的結(jié)合以及轉(zhuǎn)錄因子STAT3和RORγt對于Th117細(xì)胞的初始分化;IL---221對于Th117細(xì)胞的增殖;IL---223對于Th117細(xì)胞在外周的穩(wěn)定均發(fā)揮重要的作用。與此相反,研究發(fā)現(xiàn),Th1細(xì)胞及其分泌的IFN-γ和TTh2細(xì)胞及其分泌的IL--4能強(qiáng)烈地抑制Th117細(xì)胞的發(fā)育;與Treg細(xì)胞的功能密切相關(guān)的重要調(diào)節(jié)因子TGF-β在炎癥因子IL--6不存在的情況下能夠抑制Thl17細(xì)胞的分化,且Foxp3也可以通過下調(diào)IL-23等細(xì)胞因子的表達(dá)而抑制Th117細(xì)胞的分化�？傊�,這些Th17細(xì)胞的分化及調(diào)節(jié)因素一直是人們所關(guān)注的焦點(diǎn),也已經(jīng)成為近年來的研究熱點(diǎn)。 日本血吸蟲病作為一種典型的慢性感染性疾病的模型,能很好地誘導(dǎo)Th17細(xì)胞及Th1、Th2及Treg細(xì)胞的產(chǎn)生。尤其近年來,隨著研究的深入,已有越來越多的文獻(xiàn)報(bào)道,在血吸蟲感染中Th17細(xì)胞參與了其后期的免疫病理反應(yīng)-肝臟蟲卵肉芽腫的形成。但是截至目前,關(guān)于這些細(xì)胞亞群之間、細(xì)胞因子之間以及細(xì)胞因子與細(xì)胞之間的相互影響、相互抑制的研究多數(shù)都是在較單一實(shí)驗(yàn)因素存在的情況、基于體外研究為主獲得的結(jié)果。在一種復(fù)雜的感染過程中對于Th17細(xì)胞及其他CD4+T細(xì)胞亞群以及細(xì)胞因子之間的相互作用的動(dòng)態(tài)變化研究還很少。 因此在本研究中,我們首先建立了日本血吸蟲自然感染的小鼠模型,應(yīng)用流式細(xì)胞儀,動(dòng)態(tài)觀察了感染不同階段Th17細(xì)胞及其特征性細(xì)胞因子IL-17的水平、抑制Th17細(xì)胞的其它CD4+T細(xì)胞亞群、以及影響Th17細(xì)胞分化的相關(guān)細(xì)胞因子IFN-γ、IL-4、TGF-β、IL-6、IL-23、IL-21水平的變化并進(jìn)行綜合分析,從而探討在復(fù)雜的感染過程中Th17細(xì)胞動(dòng)態(tài)變化、以及其它CD4+T細(xì)胞亞群及細(xì)胞因子對Th17細(xì)胞可能的綜合影響。隨后,以血吸蟲感染時(shí)最主要的兩種粗分抗原SEA、SWA免疫小鼠,檢測了SEA、SWA免疫后小鼠Th17細(xì)胞及其特征性細(xì)胞因子IL-17的水平、抑制Th17細(xì)胞的其它CD4+T細(xì)胞亞群、以及影響Th17細(xì)胞分化的相關(guān)細(xì)胞因子IFN-γ、IL-4、TGF-β、IL-6、IL-23、IL-21水平的變化并進(jìn)行綜合分析,以探討SEA、SWA這兩種粗分抗原分別對Th17細(xì)胞的誘導(dǎo)作用、以及同時(shí)誘導(dǎo)產(chǎn)生的其他影響Th17細(xì)胞的CD4+T細(xì)胞亞群及細(xì)胞因子對Th17細(xì)胞可能的綜合影響。最后再給血吸蟲感染小鼠體外注射rm-IL-17細(xì)胞因子和anti-IL-17中和抗體以使感染小鼠體內(nèi)產(chǎn)生高水平和很低水平IL-17的狀態(tài),從而探討Th17細(xì)胞及IL-17是否參與了宿主的抗血吸蟲感染的保護(hù)性免疫應(yīng)答。本研究獲得如下主要結(jié)果: 1.在自然感染的過程中,當(dāng)小鼠感染3周后,隨著成蟲開始產(chǎn)卵,肝臟的蟲卵肉芽腫開始形成,并且伴隨著肝臟蟲卵肉芽腫的開始出現(xiàn),Th17細(xì)胞占CD4+T細(xì)胞的百分比略有上升,在感染5周后開始顯著上升,至感染8周時(shí)上升得最為明顯,到感染13周時(shí)上升過程趨緩,即Th17細(xì)胞的比例隨著感染的進(jìn)展基本呈現(xiàn)上升的趨勢;然而,同時(shí)Th1和Th2細(xì)胞的百分比也在上升,但是在感染的前3周Th1細(xì)胞增加的比例多于Th2細(xì)胞,相反,當(dāng)成蟲產(chǎn)卵后,Th2細(xì)胞的比例開始快速增長。同時(shí),在感染慢性期Treg細(xì)胞的百分比明顯上升。同時(shí),細(xì)胞因子檢測結(jié)果顯示:促Th進(jìn)17細(xì)胞的分化密切相關(guān)的細(xì)胞因子TGF-β、IL-6、IL-23和IL-21均隨著感染時(shí)間的增加呈現(xiàn)一種基本上升的趨勢,但同時(shí)抑制其分化的細(xì)胞因子IFN-γ和IL-4也是呈現(xiàn)穩(wěn)定上升的趨勢。以上所有結(jié)果均顯示在日本血吸蟲的自然感染過程中,全部都是由感染誘導(dǎo)的Th17細(xì)胞及促進(jìn)其產(chǎn)生的細(xì)胞因子、與Th1、Th2和Treg細(xì)胞以及抑制Th17細(xì)胞產(chǎn)生的細(xì)胞因子呈現(xiàn)一種同步增長的趨勢,提示我們這些抑制Th17細(xì)胞增長的因素在一種整體感染的情況下對Th17細(xì)胞的增長并沒有發(fā)揮明顯的抑制作用,進(jìn)而提示我們在日本血吸蟲感染后不同階段的免疫應(yīng)答狀態(tài)都是由眾多免疫效應(yīng)相互影響、彼此疊加所形成的,即在感染的情況下,體內(nèi)誘導(dǎo)因素和抑制因素同時(shí)存在,Th17細(xì)胞的增長可能是其誘導(dǎo)因素的作用強(qiáng)于抑制因素的結(jié)果。 2.采用SEA和SWA免疫小鼠后發(fā)現(xiàn)與PBS對照組相比,SEA優(yōu)勢誘導(dǎo)Th17細(xì)胞和Th2類應(yīng)答以及參與免疫負(fù)調(diào)控的Treg細(xì)胞,SWA優(yōu)勢誘導(dǎo)Th1類應(yīng)答。細(xì)胞因子檢測結(jié)果顯示與PBS對照組相比,在SEA組與Th17細(xì)胞的分化密切相關(guān)的細(xì)胞因子TGF-β、IL-6、IL-23和IL-21的水平均顯著升高;而SWA組誘導(dǎo)產(chǎn)生的細(xì)胞因子TGF-β和IL-6的水平也顯著升高,IL-23和IL-21的水平僅輕度升高。同時(shí),考慮到抑制Th17細(xì)胞的Th1、Th2、Treg細(xì)胞及抑制性細(xì)胞因子的表達(dá)水平雖然在SWA和SEA免疫后明顯升高,但考慮到抗原免疫后Th17細(xì)胞同時(shí)增多,因而推測在Th17細(xì)胞的分化中這些抑制性細(xì)胞因子可能并沒有發(fā)揮主導(dǎo)作用。 3.將小鼠腹腔注射rm-IL-17細(xì)胞因子(以模擬體內(nèi)高于正常濃度IL-17的狀態(tài))及對照PBS、或注射anti-IL-17中和抗體(以模擬體內(nèi)低于正常濃度IL-17的狀態(tài))及同型對照抗體。結(jié)果顯示,增高或降低小鼠體內(nèi)IL-17濃度都能或多或少的影響抗體應(yīng)答水平,但不能有效地增強(qiáng)(或抑制)與宿主抗血吸蟲感染高保護(hù)力密切相關(guān)的Th細(xì)胞應(yīng)答,而Treg細(xì)胞的比例卻明顯減少。根據(jù)我們現(xiàn)有的實(shí)驗(yàn)證據(jù),無法給予明確的提示來說明這些抗體及細(xì)胞水平的改變可能會(huì)對免疫保護(hù)力產(chǎn)生何種影響。雖然我們觀察到促進(jìn)與抑制Th17細(xì)胞分化的細(xì)胞因子水平大多顯著升高,但對Th17細(xì)胞本身的數(shù)量卻未見明顯的影響。然而,降低小鼠體I內(nèi)L-17濃度似乎對宿主抗血吸蟲感染的保護(hù)性免疫力有一定的提高,但根據(jù)我們目前的研究數(shù)據(jù),尚無法闡明其原因。 綜上所述,本研究中我們發(fā)現(xiàn),在自然感染過程中,Th17細(xì)胞與Th1、Th2和Treg細(xì)胞一起呈現(xiàn)一種同步增長的趨勢,提示我們Th1、Th2和Treg細(xì)胞這些在體外或單一(簡單)實(shí)驗(yàn)因素中已被廣泛證明可顯著抑制Th17細(xì)胞增長的因素在復(fù)雜的體內(nèi)感染情況下,對Th17細(xì)胞的增長并沒有發(fā)揮主導(dǎo)性的抑制作用。在粗分抗原中,我們發(fā)現(xiàn)SEA能夠優(yōu)勢誘導(dǎo)Th17細(xì)胞的產(chǎn)生(P0.05)。此外,我們還發(fā)現(xiàn)在日本血吸蟲感染過程中,Th17細(xì)胞及其分泌的細(xì)胞因子IL-17對宿主抗血吸蟲感染的免疫保護(hù)力的影響不明顯�？傊�,在一種具體而復(fù)雜的病原體感染過程中,細(xì)胞亞群之間、細(xì)胞因子之間、細(xì)胞與細(xì)胞因子之間的相互影響、相互抑制作用以及其他因子協(xié)調(diào)作用共同組成復(fù)雜的調(diào)節(jié)網(wǎng)絡(luò)調(diào)控Th17細(xì)胞分化。
[Abstract]:Non-sensitized (na (l | 1)-ve) CD ~ (4 +) T-cells can differentiate into two types of CD ~ (4 +)-effector T cells in peripheral lymphoid tissue. Th1 cells mainly secrete cytokines such as IL-2, IFN-2 and TNF-1, regulate cellular immunity, and Th2 cells mainly secrete cytokines such as IL-4, IL-5, IL-6, IL-10 and IL-13, and regulate humoral immunity. At the same time, the two are mutually inhibited, mutually adjusted, and the normal immune function of the machine body is coordinated. In recent years, a special CD ~ (4 +) T cell producing interleukin17 (IL-17) was found in some autoimmunity and allergen-specific response studies. The CD ~ (4 +) T cells have distinct characteristics with the traditional Th1 and Th2 cells. Although its function is not fully set out, more and more evidence suggests that Th17 cells play an important protective role in the host defense of some specific extracellular pathogens, such as pathogens that cannot be effectively removed by the Th1 and Th2 classes. The CD ~ (4 +) T cells can also be differentiated into a group of CD ~ (4 +) CD25 + regulatory T (Tregs, Treg) cells in addition to the three types of effector cells that are differentiated into Th1, Th2 and Th17, which mainly contact and/ or secrete some inhibitory cytokines by direct contact between the cells and the cells, Such as TGF-1 and IL-10, which play an important role in the elimination of infection and immunopathological damage. Similar to Th1 and Th2 cells, the differentiation of Th17 cells also requires specific cytokines and transcription factors The combination of TGF-1 with IL-6 and the initial differentiation of transcription factors STAT3 and STAT3 on the Th117 cells; the proliferation of IL--221 for Th117 cells; and IL--223 play an important role in the stability of Th117 cells in the periphery In contrast, the study found that Th1 cells and their secreted IFN-1 and TTh2 cells and their secreted IL-4 can strongly inhibit the development of Th117 cells, and the important regulatory factors, TGF-1, which are closely related to the function of Treg cells, can inhibit the distribution of Th17 cells in the absence of inflammatory factor IL-6. Foxp3 can also inhibit the distribution of Th117 cells by down-regulating the expression of cytokines such as IL-23. In conclusion, the differentiation and regulation factors of these Th17 cells have been the focus of attention, and have become the research heat in recent years. Point. Schistosomiasis japonica is a model of a typical chronic infectious disease, which can induce Th17 cells and Th1, Th2 and Treg cells well. In recent years, more and more literature has been reported in recent years. Th17 cells in the infection of Schistosoma japonicum have been involved in the later-stage immune-pathological reaction-liver egg granuloma. However, as of the present, studies on the interaction between these cell subpopulations, between cytokines, and between the cytokines and the cells, are mostly in the presence of a single experimental factor and are based on in vitro studies The dynamic changes of the interaction between Th17 cells and other CD4 + T cell subpopulations and cytokines in a complex infection process In this study, we first established a mouse model of the natural infection of Schistosoma japonicum, and the flow cytometry was applied to observe the level of Th17 cells and its characteristic cytokines IL-17 in different stages of infection and to inhibit the other CD4 + of Th17 cells. The changes of T-cell subpopulations and related cytokines, IFN-1, IL-4, TGF-1, IL-6, IL-23, and IL-21, which affect the differentiation of Th17 cells, and the comprehensive analysis were carried out, and the Th17 fine in complex infection was discussed. Cell dynamics, as well as other CD4 + T cell subpopulations and cytokine-to-Th17 cells The effects of SEA and SWA on the level of Th17 cells and their characteristic cytokines, IL-17, the other CD4 + T cell subpopulations of Th17 cells, and the related cytokines that affect the differentiation of Th17 cells were detected. The changes of the levels of IFN-1, IL-4, TGF-1, IL-6, IL-23, and IL-21 and the comprehensive analysis were carried out to study the induced effects of SEA and SWA on the induction of Th17 cells. And finally, the mice infected with the schistosome infected mice were injected with a rm-IL-17 cytokine and an anti-IL-17 to produce a high level and a low level of IL-17 in the infected mice, so as to explore whether the Th17 cells and the IL-17 are involved in the protection of the anti-schistosome infection of the host. sexual immune response. This study was obtained, for example, The main results were as follows:1. In the course of natural infection, when the mice were infected for 3 weeks, the egg granuloma of the liver began to form as the adults began to lay eggs, and the Th17 cells occupied the CD4 + T cells with the onset of the granuloma of the egg of the liver. The percentage of Th1 and Th2 cells increased significantly after 5 weeks of infection, most notably at 8 weeks of infection, and the increase in the increase in the rise in the 13-week period of infection, that is, the proportion of Th17 cells increased substantially with the progression of infection; however, both Th1 and Th2 cells The percentage is also rising, but the ratio of Th1 cells to increase in the first 3 weeks of the infection is more than that of the Th2 cells, in contrast, the ratio of the Th2 cells when the adult lays eggs The case began to grow rapidly. At the same time, Treg cells were infected at the same time. The results showed that the cytokines, TGF-1, IL-6, IL-23, and IL-21, which were closely related to the differentiation of Th in 17 cells, showed an increase in the time of infection. The tendency to rise substantially, but at the same time, the cytokine, IFN-1, and IL-4, which inhibit its differentiation, are also present. All of the above results are shown in the course of the natural infection of the Schistosoma japonicum, all of the Th17 cells induced by infection and the cytokines that promote their production, and the presence of one of Th1, Th2 and Treg cells as well as the cytokines that inhibit the production of Th17 cells. The trend of synchronous growth indicates that the factors that inhibit the growth of Th17 cells in the case of a whole infection do not have a significant inhibition effect on the growth of Th17 cells, thus suggesting that the immune response state of the different stages after the infection of the Schistosoma japonicum is a large number of immune responses. In the case of infection, the effect of the growth of Th17 cells is stronger than that of the induction factor. Results of the inhibition factor.2. After using SEA and SWA to immunize the mice, it was found that the SEA advantage induced the Th17 cells and the Th2 response as well as the Treg cells that were involved in the negative regulation of the immune response, and the SWA was excellent. There was a significant increase in the levels of the cytokines TGF-1, IL-6, IL-23 and IL-21, which were closely related to the differentiation of the group of SEA and Th17 cells compared with the PBS control group, and the cytokine TGF-1 and IL-21 induced by the SWA group. The levels of IL-23 and IL-2 were also significantly elevated The levels of Th1, Th2, Treg cells and inhibitory cytokines, which inhibit the Th17 cells, were only slightly increased, while the level of expression of Th1, Th2, Treg cells, and inhibitory cytokines, which inhibited the Th17 cells, increased significantly after the immunization of SWA and SEA, but taking into account T h17 cells increase at the same time, and it is presumed that these inhibitory cytokines may be present in the differentiation of Th17 cells 3. Mouse peritoneal injection of rm-IL-17 cytokine (to mimic the state of IL-17 above normal in vivo) and control PBS, or injection of anti-IL-17 neutralizing antibody (to mimic normal concentration of IL-17 in vivo) The results showed that the increase or decrease of the IL-17 concentration in the mice can more or less influence the antibody response level, but it is not effective to enhance (or inhibit) the Th cell response which is closely related to the high protective force of the host anti-schistosome infection, and the Tre The proportion of g cells is obviously reduced. According to our existing experimental evidence, it is not possible to give clear tips to indicate that changes in these antibodies and cell levels may be In spite of the significant increase in the level of cytokines that promote and inhibit the differentiation of Th17 cells, we have observed that the Th17 cells themselves However, decreasing the L-17 concentration in the body of the mouse seems to have a certain increase in the protective immunity of the host against the schistosome infection, but according to our present study In conclusion, we have found that Th17 cells, together with Th1, Th2 and Treg cells, present a synchronization in the course of natural infection. The trend of growth suggests that these factors, Th1, Th2 and Treg cells, have been widely demonstrated in in vitro or single (simple) experimental factors to significantly inhibit the growth of Th17 cells in complex in-vivo infections, with the growth of Th17 cells We found that SEA can lead to the differentiation of Th1/ Th2 cells. In addition, we found that in the course of the infection of Schistosoma japonicum, Th17 cells and their secreted cytokines IL-17 were sensitive to the host anti-schistosome. The effect of the immune protective force of the dye is not obvious. In conclusion, in a specific and complex pathogen infection process, the interaction between the cell subsets, the cytokines, the interaction between the cells and the cytokines, the mutual inhibition and the coordination of other factors together form a complex modulation.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R392
本文編號：2498885
[Abstract]:Non-sensitized (na (l | 1)-ve) CD ~ (4 +) T-cells can differentiate into two types of CD ~ (4 +)-effector T cells in peripheral lymphoid tissue. Th1 cells mainly secrete cytokines such as IL-2, IFN-2 and TNF-1, regulate cellular immunity, and Th2 cells mainly secrete cytokines such as IL-4, IL-5, IL-6, IL-10 and IL-13, and regulate humoral immunity. At the same time, the two are mutually inhibited, mutually adjusted, and the normal immune function of the machine body is coordinated. In recent years, a special CD ~ (4 +) T cell producing interleukin17 (IL-17) was found in some autoimmunity and allergen-specific response studies. The CD ~ (4 +) T cells have distinct characteristics with the traditional Th1 and Th2 cells. Although its function is not fully set out, more and more evidence suggests that Th17 cells play an important protective role in the host defense of some specific extracellular pathogens, such as pathogens that cannot be effectively removed by the Th1 and Th2 classes. The CD ~ (4 +) T cells can also be differentiated into a group of CD ~ (4 +) CD25 + regulatory T (Tregs, Treg) cells in addition to the three types of effector cells that are differentiated into Th1, Th2 and Th17, which mainly contact and/ or secrete some inhibitory cytokines by direct contact between the cells and the cells, Such as TGF-1 and IL-10, which play an important role in the elimination of infection and immunopathological damage. Similar to Th1 and Th2 cells, the differentiation of Th17 cells also requires specific cytokines and transcription factors The combination of TGF-1 with IL-6 and the initial differentiation of transcription factors STAT3 and STAT3 on the Th117 cells; the proliferation of IL--221 for Th117 cells; and IL--223 play an important role in the stability of Th117 cells in the periphery In contrast, the study found that Th1 cells and their secreted IFN-1 and TTh2 cells and their secreted IL-4 can strongly inhibit the development of Th117 cells, and the important regulatory factors, TGF-1, which are closely related to the function of Treg cells, can inhibit the distribution of Th17 cells in the absence of inflammatory factor IL-6. Foxp3 can also inhibit the distribution of Th117 cells by down-regulating the expression of cytokines such as IL-23. In conclusion, the differentiation and regulation factors of these Th17 cells have been the focus of attention, and have become the research heat in recent years. Point. Schistosomiasis japonica is a model of a typical chronic infectious disease, which can induce Th17 cells and Th1, Th2 and Treg cells well. In recent years, more and more literature has been reported in recent years. Th17 cells in the infection of Schistosoma japonicum have been involved in the later-stage immune-pathological reaction-liver egg granuloma. However, as of the present, studies on the interaction between these cell subpopulations, between cytokines, and between the cytokines and the cells, are mostly in the presence of a single experimental factor and are based on in vitro studies The dynamic changes of the interaction between Th17 cells and other CD4 + T cell subpopulations and cytokines in a complex infection process In this study, we first established a mouse model of the natural infection of Schistosoma japonicum, and the flow cytometry was applied to observe the level of Th17 cells and its characteristic cytokines IL-17 in different stages of infection and to inhibit the other CD4 + of Th17 cells. The changes of T-cell subpopulations and related cytokines, IFN-1, IL-4, TGF-1, IL-6, IL-23, and IL-21, which affect the differentiation of Th17 cells, and the comprehensive analysis were carried out, and the Th17 fine in complex infection was discussed. Cell dynamics, as well as other CD4 + T cell subpopulations and cytokine-to-Th17 cells The effects of SEA and SWA on the level of Th17 cells and their characteristic cytokines, IL-17, the other CD4 + T cell subpopulations of Th17 cells, and the related cytokines that affect the differentiation of Th17 cells were detected. The changes of the levels of IFN-1, IL-4, TGF-1, IL-6, IL-23, and IL-21 and the comprehensive analysis were carried out to study the induced effects of SEA and SWA on the induction of Th17 cells. And finally, the mice infected with the schistosome infected mice were injected with a rm-IL-17 cytokine and an anti-IL-17 to produce a high level and a low level of IL-17 in the infected mice, so as to explore whether the Th17 cells and the IL-17 are involved in the protection of the anti-schistosome infection of the host. sexual immune response. This study was obtained, for example, The main results were as follows:1. In the course of natural infection, when the mice were infected for 3 weeks, the egg granuloma of the liver began to form as the adults began to lay eggs, and the Th17 cells occupied the CD4 + T cells with the onset of the granuloma of the egg of the liver. The percentage of Th1 and Th2 cells increased significantly after 5 weeks of infection, most notably at 8 weeks of infection, and the increase in the increase in the rise in the 13-week period of infection, that is, the proportion of Th17 cells increased substantially with the progression of infection; however, both Th1 and Th2 cells The percentage is also rising, but the ratio of Th1 cells to increase in the first 3 weeks of the infection is more than that of the Th2 cells, in contrast, the ratio of the Th2 cells when the adult lays eggs The case began to grow rapidly. At the same time, Treg cells were infected at the same time. The results showed that the cytokines, TGF-1, IL-6, IL-23, and IL-21, which were closely related to the differentiation of Th in 17 cells, showed an increase in the time of infection. The tendency to rise substantially, but at the same time, the cytokine, IFN-1, and IL-4, which inhibit its differentiation, are also present. All of the above results are shown in the course of the natural infection of the Schistosoma japonicum, all of the Th17 cells induced by infection and the cytokines that promote their production, and the presence of one of Th1, Th2 and Treg cells as well as the cytokines that inhibit the production of Th17 cells. The trend of synchronous growth indicates that the factors that inhibit the growth of Th17 cells in the case of a whole infection do not have a significant inhibition effect on the growth of Th17 cells, thus suggesting that the immune response state of the different stages after the infection of the Schistosoma japonicum is a large number of immune responses. In the case of infection, the effect of the growth of Th17 cells is stronger than that of the induction factor. Results of the inhibition factor.2. After using SEA and SWA to immunize the mice, it was found that the SEA advantage induced the Th17 cells and the Th2 response as well as the Treg cells that were involved in the negative regulation of the immune response, and the SWA was excellent. There was a significant increase in the levels of the cytokines TGF-1, IL-6, IL-23 and IL-21, which were closely related to the differentiation of the group of SEA and Th17 cells compared with the PBS control group, and the cytokine TGF-1 and IL-21 induced by the SWA group. The levels of IL-23 and IL-2 were also significantly elevated The levels of Th1, Th2, Treg cells and inhibitory cytokines, which inhibit the Th17 cells, were only slightly increased, while the level of expression of Th1, Th2, Treg cells, and inhibitory cytokines, which inhibited the Th17 cells, increased significantly after the immunization of SWA and SEA, but taking into account T h17 cells increase at the same time, and it is presumed that these inhibitory cytokines may be present in the differentiation of Th17 cells 3. Mouse peritoneal injection of rm-IL-17 cytokine (to mimic the state of IL-17 above normal in vivo) and control PBS, or injection of anti-IL-17 neutralizing antibody (to mimic normal concentration of IL-17 in vivo) The results showed that the increase or decrease of the IL-17 concentration in the mice can more or less influence the antibody response level, but it is not effective to enhance (or inhibit) the Th cell response which is closely related to the high protective force of the host anti-schistosome infection, and the Tre The proportion of g cells is obviously reduced. According to our existing experimental evidence, it is not possible to give clear tips to indicate that changes in these antibodies and cell levels may be In spite of the significant increase in the level of cytokines that promote and inhibit the differentiation of Th17 cells, we have observed that the Th17 cells themselves However, decreasing the L-17 concentration in the body of the mouse seems to have a certain increase in the protective immunity of the host against the schistosome infection, but according to our present study In conclusion, we have found that Th17 cells, together with Th1, Th2 and Treg cells, present a synchronization in the course of natural infection. The trend of growth suggests that these factors, Th1, Th2 and Treg cells, have been widely demonstrated in in vitro or single (simple) experimental factors to significantly inhibit the growth of Th17 cells in complex in-vivo infections, with the growth of Th17 cells We found that SEA can lead to the differentiation of Th1/ Th2 cells. In addition, we found that in the course of the infection of Schistosoma japonicum, Th17 cells and their secreted cytokines IL-17 were sensitive to the host anti-schistosome. The effect of the immune protective force of the dye is not obvious. In conclusion, in a specific and complex pathogen infection process, the interaction between the cell subsets, the cytokines, the interaction between the cells and the cytokines, the mutual inhibition and the coordination of other factors together form a complex modulation.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R392
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 劉光偉;趙勇;;CD4~+T細(xì)胞的新亞型:Th17細(xì)胞及其生物效應(yīng)[J];生物化學(xué)與生物物理進(jìn)展;2007年04期
2 吳長有;;Th17細(xì)胞:一種新的效應(yīng)CD4~+T細(xì)胞亞群[J];細(xì)胞與分子免疫學(xué)雜志;2006年06期
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