利用芯片技术分析不同宿主感染日本血吸虫前后基因的差异性表达
|
摘要
血吸虫病是由血吸虫感染引起的分布广泛、危害严重的人兽共患寄生虫病。本研究以血吸虫易感动物小鼠、非易感动物大鼠和对血吸虫具有天然抗病作用的东方田鼠作为动物模型,应用组织化学技术观察三种动物感染血吸虫后肺、肝组织病理学变化差异,应用芯片技术和生物信息学技术等比较分析三种动物感染血吸虫前后的基因差异表达,并重点对三种动物感染血吸虫后免疫相关分子、生长发育相关分子的表达差异进行深入分析,推测三种动物对血吸虫感染的可能应答机制,具体如下:
1.对感染日本血吸虫的东方田鼠、大鼠和小鼠的肺、肝进行组织病理学观察,从组织水平了解三种动物感染日本血吸虫后肺肝组织的组织学变化差异及其引起的病理学变化差异。结果显示与适宜性宿主小鼠相比,在感染早期日本血吸虫在非适宜性宿主大鼠以及具有天然抗病作用的东方田鼠体内引起更强烈的免疫应答和病理损害,HE染色呈现免疫效应细胞以嗜酸性粒细胞为主,同时还有中性粒细胞和巨噬细胞等,这可能是东方田鼠具有先天抗日本血吸虫病的主要原因之一。
2.利用大规模、高通量的全基因组寡核苷酸芯片技术,比较分析东方田鼠、WISTAR大鼠和BALB/c小鼠感染日本血吸虫前后肺和肝组织基因表达差异,应用SpotDataTM Pro V3.0软件和聚类软件对数据进行分析,采用实时定量PCR法进行验证。芯片杂交结果如下:
(1).攻虫感染十天后,东方田鼠、大鼠和小鼠与感染前相比肺上调基因数分别为2678、1980和364条;下调表达的基因数分别为1478、2306和16条;相应的肝上调表达基因基因数分别为330、1655和111条;下调表达基因数分别为190、540和179条。选择6个芯片杂交显示差异表达基因进行real time PCR验证,结果和芯片基本相符。
(2).分别筛选三种宿主肺中显著变化(Cy5/Cy3≥2.0和Cy5/Cy3≤0.5)的同源基因进行分层聚类分析,发现这类差异基因有1334条,为东方田鼠显著变化、大鼠相对变化而小鼠基本保持不变的基因。go的功能分析显示这些差异基因主要参与信号转导(signal transduction)、转录调节活性(transcription regulator activity)、细胞粘附(cell adhesion)、细胞凋亡(apoptosis)等;而肝中这类差异基因有265条,涉及细胞骨架构成(cytoskeleton construction)、催化活性(catalytic activity)、代谢作用(metabolism)、细胞分化(cell differentiation)、免疫应答(immune response)、生长发育(growth and development)等。
(3).通过聚类分析发现,肺肝组织共同差异表达基因有74条,其中东方田鼠显著上调基因46条,显著下调基因28条,这些基因主要参与了信号转导(Msr1、Scarb1、Pnrc1)、基因转录调控(Cnot2、Znrd1、Cited2、Xbp1、Gpbp1)、免疫应答(C1qa、C1ra、C1rb、Psmb8、Itgb2)等。
(4).感染日本血吸虫10d时东方田鼠肺、肝中一些与免疫相关的基因和一些细胞凋亡诱导基因表达上调,如肺中的补体成分1q(C1qa)、补体成分8a (C8a)、组织蛋白酶S(Ctss)、免疫球蛋白γFc受体1(cgr1)和免疫球蛋白γFc受体3 (cgr3)等;肝中有干扰素调节因子7(IRF-7)、组织蛋白酶S(Ctss)、CD74等;编程性细胞死亡6(Pdcd6)、半胱天冬酶7(Casp7)、酪氨酸蛋白激酶2(Jak2)等。而一些与生长发育相关的重要分子则在东方田鼠呈下调表达,如肺内甲状腺激素受体α(Thrα)、甲状腺激素应答基因(Thrsp)和类固醇11β脱氢酶1(Hsd11β1)基因,肝中胰岛素样生长因子1(IGF-1)基因。
(5).对基因表达谱进行深入分析还提示三种宿主肺、肝组织对血吸虫感染可能有不同的应答机制,东方田鼠通过Jak-STAT、VEGF、Notch以及FcεRⅠ等信号途径介导;大鼠通过补体级联途径介导;小鼠则通过多种细胞因子(主要是趋化因子和TNF)相互作用及Ca~(2+)信号途径介导。
本研究对深入探索东方田鼠抗日本血吸虫病的分子机理、发现东方田鼠抗血吸虫病的关键分子、阐明血吸虫与宿主的相互作用关系、开拓抗血吸虫疫苗和药物研究新途径都具有重要意义。
Schistosomiasis caused by schistosome, is a wide spread parasitic zoonosis that causes serious healthy problem to both human and animals. The research useed mouse, a susceptible host of schistosome, rat, a unsusceptible host, and Microtus fortis, a resistant host, as animal model. After challenge infection, the histopathological change in lungs and livers of the three kinds of animal was observated with histochemistry technique. Gene difference expression was analysed and compared with microarray and bioinformatics technique. The dissertation focused on the different expression of immune-associated genes and development-associated genes and infered the possible response mechanisms of three kinds of animal infected with schistosome. The results were as follows:
The histopathological change in lungs and livers of Microtus fortis, rat and mouse were observed by hematoxylin-eosin stain and Olympus light microscope.The Schistosoma japonicum caused more intensive immune response and pathological lesion in the body of Microtus fortis and rat than mouse, the susceptible host. Hematoxylin-eosin stain showed that the immune effector cells nearly were eosinophile granulocyte, supplemented by heterophil granulocyte, macrophage, et al, which may be one of the main reasons why Microtus fortis can naturally resist to Schistosoma japonicum.
Gene difference expression of the lung and the liver tissues between Microtus fortis,rats and mice infected with Schistosoma japonicum for 10d were analyzed by oligonucleotide chip.Data analysis was performed on the basis of a significant two-fold change in signal using SpotDataTM Pro V3.0 and cluster3.0 software in order to find out gene function cluster associated with schistosomiasis resistence.Real-time PCR were used for validation. The chief results are showed as fo11ows:
Ten days after challenge infection, in Microtus fortis,2678 lung and 330 liver genes with Gene Ontology annotation were up-regulated and 1748 lung and 190 liver genes were down-regulated in comparison with controls;in rats,1980 lung and 1655 liver genes were up-regulated and 2306 lung and 540 liver genes were down-regulated;in mice,364 lung and 111 liver genes were up-regulated and 16 lung and 179 liver genes were down-regulated. The differential expression was validated in 6 randomly selected genes using quantitative RT-PCR.
Homologous genes of Microtus fortis,rats and mice are highlighted on the basis of a significant(Cy5/Cy3≥2.0或≤0.5). Hierarchy cluster analysis showed that 1334 lung genes were identified as differentially regulated, which were significant different in Microtus fortis, relatively different in rats and nearly basically fixed in mouse. These genes could be functionally categorized into signal transduction,transcription regulator activity,signal,cell adhesion and apoptosis. These kind of genes in liver could be functionally categorized into cytoskeleton construction,catalytic activity,metabolism,cell differentiation, immune response, growth and development. Cluster analysis showed that 74genes,including Msr1,Cnot2,C1qa,Psmb8,Itgb2,and so on,were identified as differentially regulated between the two groups.
Some immune-associated genes (such as C1qa, C8a, Ctss, cgr1, cgr3, IRF-7 and CD74) in Microtus fortis infected with Schistosoma japonicum for 10 days were up-regulated. Some development-associated genes (such as Thrα, Thrsp, Hsd11β1 and IGF-1) were down-regulated while some apoptosis induction genes (such as Pdcd6, Casp7, Jak2) were up-regulated.
The profound analysis on gene expression pattern suggests that the lung tissues and liver tissues of three hosts infected with Schistosoma japonicum have different response mechanisms. Microtus fortis induces immune response via Jak-STAT, VEGF, Notch and FcεR. Rat induces immune response via complement cascade pathway. Mouse induces immune response via Ca~(2+) signal pathway and the interreaction between chemotatic factor and TNF.
The results reported here were meaningful for exploring the molecular mechanism of schistosoma-resistance of M.fortis , finding out the key molecule of resisting to Schistosoma japonicum, elucidate the interaction between Schistosoma japonicum and its host, bringing out a new way to develop anti-schistosomula vaccines and drugs.
1.对感染日本血吸虫的东方田鼠、大鼠和小鼠的肺、肝进行组织病理学观察,从组织水平了解三种动物感染日本血吸虫后肺肝组织的组织学变化差异及其引起的病理学变化差异。结果显示与适宜性宿主小鼠相比,在感染早期日本血吸虫在非适宜性宿主大鼠以及具有天然抗病作用的东方田鼠体内引起更强烈的免疫应答和病理损害,HE染色呈现免疫效应细胞以嗜酸性粒细胞为主,同时还有中性粒细胞和巨噬细胞等,这可能是东方田鼠具有先天抗日本血吸虫病的主要原因之一。
2.利用大规模、高通量的全基因组寡核苷酸芯片技术,比较分析东方田鼠、WISTAR大鼠和BALB/c小鼠感染日本血吸虫前后肺和肝组织基因表达差异,应用SpotDataTM Pro V3.0软件和聚类软件对数据进行分析,采用实时定量PCR法进行验证。芯片杂交结果如下:
(1).攻虫感染十天后,东方田鼠、大鼠和小鼠与感染前相比肺上调基因数分别为2678、1980和364条;下调表达的基因数分别为1478、2306和16条;相应的肝上调表达基因基因数分别为330、1655和111条;下调表达基因数分别为190、540和179条。选择6个芯片杂交显示差异表达基因进行real time PCR验证,结果和芯片基本相符。
(2).分别筛选三种宿主肺中显著变化(Cy5/Cy3≥2.0和Cy5/Cy3≤0.5)的同源基因进行分层聚类分析,发现这类差异基因有1334条,为东方田鼠显著变化、大鼠相对变化而小鼠基本保持不变的基因。go的功能分析显示这些差异基因主要参与信号转导(signal transduction)、转录调节活性(transcription regulator activity)、细胞粘附(cell adhesion)、细胞凋亡(apoptosis)等;而肝中这类差异基因有265条,涉及细胞骨架构成(cytoskeleton construction)、催化活性(catalytic activity)、代谢作用(metabolism)、细胞分化(cell differentiation)、免疫应答(immune response)、生长发育(growth and development)等。
(3).通过聚类分析发现,肺肝组织共同差异表达基因有74条,其中东方田鼠显著上调基因46条,显著下调基因28条,这些基因主要参与了信号转导(Msr1、Scarb1、Pnrc1)、基因转录调控(Cnot2、Znrd1、Cited2、Xbp1、Gpbp1)、免疫应答(C1qa、C1ra、C1rb、Psmb8、Itgb2)等。
(4).感染日本血吸虫10d时东方田鼠肺、肝中一些与免疫相关的基因和一些细胞凋亡诱导基因表达上调,如肺中的补体成分1q(C1qa)、补体成分8a (C8a)、组织蛋白酶S(Ctss)、免疫球蛋白γFc受体1(cgr1)和免疫球蛋白γFc受体3 (cgr3)等;肝中有干扰素调节因子7(IRF-7)、组织蛋白酶S(Ctss)、CD74等;编程性细胞死亡6(Pdcd6)、半胱天冬酶7(Casp7)、酪氨酸蛋白激酶2(Jak2)等。而一些与生长发育相关的重要分子则在东方田鼠呈下调表达,如肺内甲状腺激素受体α(Thrα)、甲状腺激素应答基因(Thrsp)和类固醇11β脱氢酶1(Hsd11β1)基因,肝中胰岛素样生长因子1(IGF-1)基因。
(5).对基因表达谱进行深入分析还提示三种宿主肺、肝组织对血吸虫感染可能有不同的应答机制,东方田鼠通过Jak-STAT、VEGF、Notch以及FcεRⅠ等信号途径介导;大鼠通过补体级联途径介导;小鼠则通过多种细胞因子(主要是趋化因子和TNF)相互作用及Ca~(2+)信号途径介导。
本研究对深入探索东方田鼠抗日本血吸虫病的分子机理、发现东方田鼠抗血吸虫病的关键分子、阐明血吸虫与宿主的相互作用关系、开拓抗血吸虫疫苗和药物研究新途径都具有重要意义。
Schistosomiasis caused by schistosome, is a wide spread parasitic zoonosis that causes serious healthy problem to both human and animals. The research useed mouse, a susceptible host of schistosome, rat, a unsusceptible host, and Microtus fortis, a resistant host, as animal model. After challenge infection, the histopathological change in lungs and livers of the three kinds of animal was observated with histochemistry technique. Gene difference expression was analysed and compared with microarray and bioinformatics technique. The dissertation focused on the different expression of immune-associated genes and development-associated genes and infered the possible response mechanisms of three kinds of animal infected with schistosome. The results were as follows:
The histopathological change in lungs and livers of Microtus fortis, rat and mouse were observed by hematoxylin-eosin stain and Olympus light microscope.The Schistosoma japonicum caused more intensive immune response and pathological lesion in the body of Microtus fortis and rat than mouse, the susceptible host. Hematoxylin-eosin stain showed that the immune effector cells nearly were eosinophile granulocyte, supplemented by heterophil granulocyte, macrophage, et al, which may be one of the main reasons why Microtus fortis can naturally resist to Schistosoma japonicum.
Gene difference expression of the lung and the liver tissues between Microtus fortis,rats and mice infected with Schistosoma japonicum for 10d were analyzed by oligonucleotide chip.Data analysis was performed on the basis of a significant two-fold change in signal using SpotDataTM Pro V3.0 and cluster3.0 software in order to find out gene function cluster associated with schistosomiasis resistence.Real-time PCR were used for validation. The chief results are showed as fo11ows:
Ten days after challenge infection, in Microtus fortis,2678 lung and 330 liver genes with Gene Ontology annotation were up-regulated and 1748 lung and 190 liver genes were down-regulated in comparison with controls;in rats,1980 lung and 1655 liver genes were up-regulated and 2306 lung and 540 liver genes were down-regulated;in mice,364 lung and 111 liver genes were up-regulated and 16 lung and 179 liver genes were down-regulated. The differential expression was validated in 6 randomly selected genes using quantitative RT-PCR.
Homologous genes of Microtus fortis,rats and mice are highlighted on the basis of a significant(Cy5/Cy3≥2.0或≤0.5). Hierarchy cluster analysis showed that 1334 lung genes were identified as differentially regulated, which were significant different in Microtus fortis, relatively different in rats and nearly basically fixed in mouse. These genes could be functionally categorized into signal transduction,transcription regulator activity,signal,cell adhesion and apoptosis. These kind of genes in liver could be functionally categorized into cytoskeleton construction,catalytic activity,metabolism,cell differentiation, immune response, growth and development. Cluster analysis showed that 74genes,including Msr1,Cnot2,C1qa,Psmb8,Itgb2,and so on,were identified as differentially regulated between the two groups.
Some immune-associated genes (such as C1qa, C8a, Ctss, cgr1, cgr3, IRF-7 and CD74) in Microtus fortis infected with Schistosoma japonicum for 10 days were up-regulated. Some development-associated genes (such as Thrα, Thrsp, Hsd11β1 and IGF-1) were down-regulated while some apoptosis induction genes (such as Pdcd6, Casp7, Jak2) were up-regulated.
The profound analysis on gene expression pattern suggests that the lung tissues and liver tissues of three hosts infected with Schistosoma japonicum have different response mechanisms. Microtus fortis induces immune response via Jak-STAT, VEGF, Notch and FcεR. Rat induces immune response via complement cascade pathway. Mouse induces immune response via Ca~(2+) signal pathway and the interreaction between chemotatic factor and TNF.
The results reported here were meaningful for exploring the molecular mechanism of schistosoma-resistance of M.fortis , finding out the key molecule of resisting to Schistosoma japonicum, elucidate the interaction between Schistosoma japonicum and its host, bringing out a new way to develop anti-schistosomula vaccines and drugs.
引文
[1]陈贤义,姜庆五,王立英,等.2001年全国血吸虫病疫情通报[J].中国血吸虫病防治杂志, 2002, 14 (4):241-243.
[2]周述龙,林建银,蒋明森.血吸虫学[M].北京科学出版社, 2001.
[3]郝阳,吴晓华,夏刚,等, 2004年全国血吸虫病疫情通报.中国血吸虫病防治杂志,2005,7(6):401-404.
[4]郑江.关于我国血吸虫病防治的策略问题[J].热带医学杂志,2006 ,6 (12):1237-1239.
[5]于恩庶.中国人畜共患病学[M].福建科学技术出版社,1988,676-686.
[6] Lanzer M, Gross U. Mechanisms of parasite persistence and immune evasion[J]. Parasitol Today, 1997, 13 (2):123-125
[7] Fishelson Z. Novel mechanism of immune evasion by Schistosoma mansoni[J]. Mem Inst 1995, 9(5):289-292.
[8] Fishelson Z, Amiri P, Friend DS,et al.Schistosoma mansoni: cell-specific expression and secretion of a serine protease during development of cercariae[J]. Exp Parasitol, 1992,75(3):87-98.
[9] Cocude C, Pierrot C, Cetre C,et al. Molecular characterization of a partial sequence encoding a novel Schistosoma mansoniserine protease[J].J Parasitol, 1997,115:395-402.
[10] Ghendler Y, Parizade M, Arnon R,et al.Schistosoma mansoni:Evidence for a 28 kDa membrane-anchored protease on schistosomula[J].Exp Parasitol, 1996,83:73-82.
[11] Ghendler Y, Arnon R, Fishelson Z.Schistosoma mansoni: Isolation and characterization of Smpi56, a novel serine protease inhibitor[J]. Exp Parasitol, 1994,78:121-131.
[12] Ghendler Y, Arnon R, Fishelson Z.Schistosoma mansoni: Isolation and characterization of Smpi56, a novel serine protease inhibitor[J]. Exp Parasitol, 1994,78:121-131.
[13] Horta MF, Ramalho-Pinto FJ. Role of human decay accelerating factor in the evasion ofSchistosoma mansonifrom the complement-mediated killingin vitro[J]. J Exp Med, 1992,175:619.
[14] Parizade M, Arnon R, Lachmann PJ,et al. Functional and antigenic similarities between a 94 kD protein ofSchistsoma mansoni(SCIP-1) and human CD59[J]. J Exp Med, 1994,179:1625-1636
[15] Duvaux-Miret O, Stefano GB. Proopiomelanocortin-derived peptides as tools of immune evasion for the human trematode Schistosoma mansoni [J]. Acta Biol Hung, 1992,43:281-286.
[16] Duvaux-Miret O, Capron A. Proopiomelanocortin in helminth Schistosoma mansoni. synthesis ofβ-endorphin, ACTH andα-MSH. existence of POMC-related sequences[J]. Annals of the New York Academy of Sciences, 1992,650:245-250.
[17] Salzet M, Capron A, Stefano GB. Molecurlar crosstalk in host-parasite relationships: schistosome and Leech-host interactions[J]. Parasitol Today, 2000,16:536-540.
[18] Salzet M. Invertebrate molecular neuroimmune processes [J]. Brain Review, 2000,34: 69-79.
[19] Pearce EJ, Sher A. Functional dichotomy in CD4+T cell response to Schistosoma mansoni[J]. Exp Parasitol, 1991,73: 463-472.
[20] Pearce EJ, Caspar P, Grzych JM,et al. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by parasitic helminth Schistosoma mansoni[J]. J Exp Med, 1991,173:159-166.
[21] Duvaux-Miret O, Stefano GB, Smith EM, et al. Immunosup pression in the definitive and intermediate hosts of the human parasite Schistosoma mansoniby release of immunoactive neuropeptides[J]. Proc Natl Acad Sci USA, 1992,89:778-781.
[22] Leung MK, Dissous C, Capron A,et al. Schistosoma mansoni: the presence and potential use of opiate-like substances[J]. Exp Parasitol,1995,81:208-15.
[23] Pryor SC, Elizee R. Evidence of opiates and opiod neuropeptides and their immune effects in parasitic invertebrates representing three phyla: Schistosoma mansoni, Theromyzon tessulatum, Trichinella spiralis[J].Acta Biol Hung, 2000,51:331-341.
[24] Xavier EM, Lucena-Silva N, Werkhauser RP,et al. The tegument of Schistosoma mansoni: genes, antigens and the host-parasite relationship[J]. Mem Inst Oswaldo Cruz, 1998,93(Suppl):85-86.
[25] Abath FG, Werkhauser RC. The tegument ofSchistosoma mansoni: functional and immunological features[J]. Parasit Immunol, 1996,18:15-20.
[26] Brouwers JF, Skelly PJ, Van Golde LM,et al. Studies on phospholipid turn over argue against sloughing of tegument membranes in adult Schistosoma mansoni[J]. Parasitology, 1999,119(pt3):287-294.
[27] Simpson AJG. Schistosome surface antigens: development expression and immunological function[J]. Parasitol Today, 1990,6:40-45.
[28] Mountford AP, Trottein F. Schistosomes in the skin: a balance between immune priming and regulation[J]. Trends in Parasitology, 2004,20(5):221-226.
[29] Francois T, Sophie N, Ve ronique A. Schistosoma mansoni schistosomula reduce E-selectin and VCAM-1 expression in TNF-α-simulated lung Microvascular endothelial cells by interfering with the NF-κB pathway[J].Eur J Immuol,1999, 29(11):3691-3701
[30] Tato C, Hunter C. Host-pathogen Interactions: Subversion and Utilization of the NF-κB Pathway during Infection[J]. Infection and immunity,2002,70(7):3311-3317.
[31] Capron A, Riveau G, Carpron M. Schistosomes: the road from host-parasite interactions to vaccines in clinical trials[J].Trends in Parasitology, 2005,21(3):143-149
[32]李浩.何艳燕,林矫矫,等.东方田鼠抗日本血吸虫现象的观察[J].中国兽医寄生虫病,2000,8(2):12—15.
[33]李浩.何艳燕,林邦发,等.东方田鼠重复感染日本血吸虫试验初步研究[J].中国兽医寄生虫病,2001,9(3):15—17.
[34]朱国正,汪英华,雷观愚,等.东方田鼠的实验室饲养及其抗血吸虫感染特性[J].上海实验动物科学,1991,ll(4):l93—198.
[35]王庆林,易新元,曾宪芳,等.东方田鼠感染日本血吸虫后肺和肝的组织细胞反应及虫体的扫描电镜观察.中国人兽共患病杂志,2002,18(4):65～67.
[36]李浩,何艳燕,林矫矫,等.东方田鼠抗日本血吸虫病现象的观察.中国兽医寄生虫病,2000,8(2):12～15.
[37]王庆林,易新元,曾宪芳,等.东方田鼠感染日本血吸虫后肺和肝的组织细胞反应及虫体的扫描电镜观察.中国人兽共患病杂志,2002,18(4):65～67.
[38] Zhou XN, Chen MG, Don MM, et al. Schistosomiasis control in the 21st century proceedings of the international symposium on schistosomiasis,Shanghai. July 4-6,2001.Acta Tropica, 2002(82): 95～114.
[39]张新跃,何永康,李毅,等.正常东方田鼠血清及脾细胞体外杀血吸虫童虫作用的初步观察[J].中国血吸虫病防治杂志。2001,13(4):206—208.
[40]刘金明,傅志强,李浩,等.东方田鼠血清体外杀伤日本血吸虫童虫效果的初步观察[J].中国人兽共患病杂志,2002,18(2):82—84.
[41] He Y,Luo X,Zhang X,et al. Immunological characteristics of natural resistance in Microtus fortis to infection with Schistosoma japonicum [J].Chin Med J,1999,112(7):649—654
[42]何永康,罗新松,张新跃,等.东方田鼠天然抗血吸虫感染免疫特性的研究.中国血吸虫病防治杂志,1998,10(增刊):73～77.
[43]蒋守富,魏梅雄,林娇娇,等.东方田鼠抗日本血吸虫抗体IgG亚类的初步研究.中国血吸虫病防治杂志,2001,13(1):1～3.
[44]傅志强,刘金明,蒋守富,等.东方田鼠抗日本血吸虫抗体水平监测与分析.中国兽医寄生虫病,2001,9(4):6～8.
[45]张新跃,何永康,李毅,等.正常东方田鼠血清及脾细胞体外杀血吸虫童虫作用的初步观察[J].中国血吸虫病防治杂志。2001,13(4):206—208.
[46]刘金明,傅志强,李浩.东方田鼠ADCC体外杀伤日本血吸虫童虫效果的初步观察[J].寄生虫与医学昆虫学报,2001,8(4):212—219.
[47]罗新松,何永康等,东方田鼠血清被动转移小白鼠抗血吸虫感染的保护性研究[J].中国人兽共患病杂志,1998,14(5): 75-76.
[48] Vignali DA, Bickle QD, Taylor MG, et al. Comparision of the role of complement in immunity to Schistosoma mansoni in rats and mice. Immunology. 1988, 63(1): 55-61.
[49]刘金明,傅志强,李浩,等.东方田鼠血清体外杀伤日本血吸虫童虫效果的初步观察.中国人兽共患病杂志,2002,18(2):82-84.
[50] Widmer MB. Regulation of cytolytic T-lymphocyte generation by B cell stimulatory factor. Nature, 1987, 326:795.
[51] Snapper CM, Finkelman FD, Paul WE. Differential regulation of IgG1 and IgE synthesis by interleukin 4. The Journal of Experimental Medicine, 1988,167:183.
[52]何永康,罗新松,张新跃,等.东方田鼠天然抗血吸虫感染免疫特性的研究.中国血吸虫病防治杂志,1998,10(增刊):73～77.
[53]阎玉涛,刘述先,宋光承,等.东方田鼠天然抗体相关的日本血吸虫抗原基因筛选和克隆.中国寄生虫学与寄生虫病杂志,2001(19):153～156.
[54]张亮,程国锋,傅志强,等.血吸虫新抗原基因SjMF4的克隆、表达及功能分析.生物化学与生物物理学报,2003,35(12):1099～1104.
[55]王庆林,易新元,曾宪芳,等.东方田鼠感染血清免疫筛选日本血吸虫成虫cDNA文库.中国生物化学与分子生物学学报,2001,17(5):547～551.
[56]欧阳理,王庆林,曾宪芳,等.从随机多肽库中筛选日本血吸虫抗原模拟表位诱导保护性免疫的研究.中国热带医学,2002,2(2):132～135.
[57] Shoemaker DD, Schad, A rmour CD, et al. Experimental annotation of the human genome using microarray technology. Nature, 2001; 409 (6822) : 922-927.
[58]安利峰,胜利.基因芯片及其应用进展[J].西北民族学院学报,2002,23:40-42.
[59]马旭.基因芯片技术及其研究现状和应用前景[J].中国医疗器械信息,2002,8(l):4-7.
[60] Jells CL.Defining critical residues in the epitope for HIV-neutralizing monoclonal antibody using phage display and peptide array technologies. Gene ,1993,137910:63-68
[61] Heller RA,Schena M,Chai A et al.Discovery and analysis of inflammatory disease-related genes using cDNA microarrays.Proc Natl Acad Sci USA,1997,94:2150-2155
[62] XZ Wang, J J Lin,XG Feng, Gene expression patterns during development of schistosoma japoncium in mamman host〔J〕.Mol Bio parasitol (under review)
[63] Nisbet A J,Gasse R B. Profiling of gender-specific gene expression for Trichostrongylus vitrinus(Nematoda:Strongylida)by microarray analysis of expressed sequence tag libraries constructed by suppressive-subtractive hybridization〔J〕. Int J Parasitol,2004,34:633 - 643.
[64]季旻珺,苏川等,日本血吸虫感染过程中抑制性因子的表达特征[J].中国人兽共患病杂志,2005,21(5): 379-382
[65] Morimoto M,Zarlenga D,Beard H,et al. Ascaris suum:cDNA microarray analysis of 4th stage larvae(L4)during self-cure from the intestine〔J〕. Exp Parasitol,2003,104(3 - 4):113 - 121.
[66] Deng M,Lancto C A,Abrahamsen M S. Cryptosporidium parvum regulation of human epithelial cell gene expression. International〔J〕. Int J Parasitol,2004,34:73 - 82.
[67] Celis J E,Kruhoffer M,Gromova I,et al. Gene expression profiling:monitoring transcription and translation products using DNA microarrays and proteomics〔J〕. FEBS Lett,2000,480(1):2 - 16.
[68]何毅勋,杨惠中,毛守白.日本血吸虫宿主特异性研究之一:各哺乳动物体内虫体的发育率、分布及存活情况[J].中华医学杂志,1960,46(6):470-475.
[69] Fukuda K,Fujino T,Oguma T et a1.Studies on host specificity in Paragonimus westermani:ultrastructural study of inflammatory reactions to the parasite in rat muscles[J].Int J Parasitol,1993,23(6):757-763.
[70]何毅勋,郁平,郁琪芳。等.不同宿主感染日本血吸虫尾蚴的皮肤组织反应[J].中国奇生虫学与奇生虫病杂志,1989,7(1):15-18.
[71] Kojima S,Yamamoto N,Kanazawa T et a1.Monoclonal IgE—dependent eosinophil cytotoxicity to haptenated schistosomula of Schistosoma japonicum:enhancement of the cytotoxicity and expressaion of Fc receptors for IgE by Nippostrongy brasiliensis infection[J].J Immunol,1985,134(4):2719～2722.
[72]张弘,徐亚雄.嗜酸性粒细胞在日本血吸虫(中国大陆株)感染小鼠体内的作用[J].中国血吸虫病防治杂志,1993,5(2):86～90.
[73] Meeusen ENT and balic A.Do eosinophils have a role in the killing of helminth parasites[J].Parasitol Today,2000,16(3):95～101.
[74] Chitsulo L,Engels D,Montresor A,et a1.The global status of schistosomiasis and its control[J].Acta Trop,2000,77(1):41—51.
[75]贺宏斌,左家铮,周利红,等.东方田鼠实验感染日本血吸虫的研究[J].湖南医学,1992,9(2):65—67.
[76]黎申恺,朱祖林,金壁如,等.1965.东方田鼠对日本血吸虫的不感染性[J].寄生虫学报,2(1):103～105.
[77]刘杰生,容寿铭,陈佩玑,等.几种鼠类人工感染日本血吸虫的实验观察.中国血吸虫病防治杂志,1992,4(6):350～351
[78]李浩,何艳燕,林矫矫,等.东方田鼠抗日本血吸虫病现象的观察[J].中国兽医寄生虫病,2000,8(2):12-15.
[79] V. Tusher, R. Tibshirani, and G. Chu. Significance analysis of microarrays applied to transcriptional responses to ionizing radiation. [J]. Proc. Natl. Acad. Sci. USA,2001., 98:5116–5121,
[80]孙军,林矫矫,程国锋,等.利用基因表达谱芯片研究东方田鼠和小鼠感染日本血吸虫前后基因的差异性表达[J].北京大学学报(自然科学版),2004,40(4):532～537.
[81] Attila L. Szvetko, Ashleigh Jones, An investigation of the C77G and C772T variations within the human protein tyrosine phosphatase receptor type C gene for association with Multiple Sclerosis in an Australian population[J].Brain Research,2003,2 (5):154—158.
[82] Badovinac VP,Tvirnnereim AR,Harry JT.Regulation of antigen specific CD8+ T cell homeostasis by perforin and interferon-β[J].Science,2000,290(5495):1354—1358.
[83] Byungsuk Kwon, Byung-S Youn, Byoung S Kwon. Functions of newly identified members of the tumor necrosis factor receptor/ligand superfamilies in lymphocytes [J].Current Opinion in Immunology, 1999,11,(3): 340-345
[84] Ken B. Reid, Maurice Colomb, Franz Petry. Complement component C1 and the collectins– first-line defense molecules in innate and acquired immunity[J].Trends in Immunology, 2002,23,(3):115-117
[85] Hogarth PM, Hulett MD, Osman N. Fcγreceptor : gene structure and receptor function [J ]. Immunol Res ,1992,11: 217～225.
[86] HIBBS ML , SELVARAJ P, CARPEN O , et al. Mechanisms for regulating expression of membrane isoforms of FcγrIII (CD16) [ J ]. Science,1989, 246:1608 -1611.
[87] Butterworth AE,Dunne DW.Fulford AJ,et al. Human immunity to Schistosoma mansoni:observation On mechanisms and implications for control[J].Immunot Invest.1992,91(5):391-396.
[88] Ph. Berthelot, C. Guglielminotti, A. Fresard, F. Zeni, F. Lucht .Les immunoglobulines en thérapeutique anti-infectieuse [ J ]. Médecine et Maladies Infectieuses, 1998, 28(5): 414-417
[89] Stanislava Stosic-Grujicic, Ivana Stojanovic, Ferdinando Nicoletti .MIF in autoimmunity and novel therapeutic approaches [ J ].Autoimmunity Reviews, 2009, 8, (3):244-249
[90] E. Mamessier, K. Botturi, D. Vervloet, A. Magnan.Lymphocytes T régulateurs, atopie et asthme : un nouveau concept en trois dimensions [ J ].Revue des Maladies Respiratoires, 2005,22, (2), : 305-311.
[91] Matthew J. Cotter, Daniel A. Muruve. Isolation of neutrophils from mouse liver: A novel method to study effector leukocytes during inflammation[ J ].Journal of Immunological Methods, 2006,312 (30) :68-78
[92] Travis R. Wolter, Randall Wong, Suparna A. Sarkar .DNA microarray analysis for the identification of innate immune pathways implicated in virus-induced autoimmune diabetes [ J ].Clinical Immunology, 2004,3 (30) :248-253
[93] LIU W, SPERO D M. Cysteine protease cathepsin S as a key step in antigen presentation[J].Drug News Perspect,2004,17:357-363
[94] Richard J. Riese, Paula R. Wolf, Dieter Br?mme,et al. Essential Role for Cathepsin S in MHC Class II–Associated Invariant Chain Processing and Peptide Loading [J].Immunity, 1996, 4(4), 357-366
[95] Renaud Seigneuric, Maud H.W. Starmans. Impact of supervised gene signatures of early hypoxia on patient survival[J].Radiotherapy and Oncology, 2007,83, (3):374-382 .
[96] Lo CG, Lu TT, Cyster JG. Integrin-dependence of lymphocyte entry into the splenic white pulp [J].J Exp Med, 2003,197(3):353-361
[97] Saule P,Adriaenssens E,Delacre M,et al. Early variations of host thyroxine and interleukin-7 favor Schistosoma mansoni development. [J]. J Parasito1.2002,88(5):849—855
[98] Briggs MH.metabolism of steroid hormones by Schistosomes [J].Biochim Biophys Acta,1972,280:481—485.
[99] Wei Hu, Qing Yan, Da-Kang Shen.Evolutionary and biomedical annotation of schistosoma japonicum complementary DNA resourceNature[J].Genetics,2003,35:139～147
[100]贾人初,孙毅,刘金明,日本血吸虫童虫裂解物对东方田鼠肝脏T7噬菌体展示cDNA文库的筛选及阳性克隆分析[J].生物工程学报2008,24(5):733-739
[2]周述龙,林建银,蒋明森.血吸虫学[M].北京科学出版社, 2001.
[3]郝阳,吴晓华,夏刚,等, 2004年全国血吸虫病疫情通报.中国血吸虫病防治杂志,2005,7(6):401-404.
[4]郑江.关于我国血吸虫病防治的策略问题[J].热带医学杂志,2006 ,6 (12):1237-1239.
[5]于恩庶.中国人畜共患病学[M].福建科学技术出版社,1988,676-686.
[6] Lanzer M, Gross U. Mechanisms of parasite persistence and immune evasion[J]. Parasitol Today, 1997, 13 (2):123-125
[7] Fishelson Z. Novel mechanism of immune evasion by Schistosoma mansoni[J]. Mem Inst 1995, 9(5):289-292.
[8] Fishelson Z, Amiri P, Friend DS,et al.Schistosoma mansoni: cell-specific expression and secretion of a serine protease during development of cercariae[J]. Exp Parasitol, 1992,75(3):87-98.
[9] Cocude C, Pierrot C, Cetre C,et al. Molecular characterization of a partial sequence encoding a novel Schistosoma mansoniserine protease[J].J Parasitol, 1997,115:395-402.
[10] Ghendler Y, Parizade M, Arnon R,et al.Schistosoma mansoni:Evidence for a 28 kDa membrane-anchored protease on schistosomula[J].Exp Parasitol, 1996,83:73-82.
[11] Ghendler Y, Arnon R, Fishelson Z.Schistosoma mansoni: Isolation and characterization of Smpi56, a novel serine protease inhibitor[J]. Exp Parasitol, 1994,78:121-131.
[12] Ghendler Y, Arnon R, Fishelson Z.Schistosoma mansoni: Isolation and characterization of Smpi56, a novel serine protease inhibitor[J]. Exp Parasitol, 1994,78:121-131.
[13] Horta MF, Ramalho-Pinto FJ. Role of human decay accelerating factor in the evasion ofSchistosoma mansonifrom the complement-mediated killingin vitro[J]. J Exp Med, 1992,175:619.
[14] Parizade M, Arnon R, Lachmann PJ,et al. Functional and antigenic similarities between a 94 kD protein ofSchistsoma mansoni(SCIP-1) and human CD59[J]. J Exp Med, 1994,179:1625-1636
[15] Duvaux-Miret O, Stefano GB. Proopiomelanocortin-derived peptides as tools of immune evasion for the human trematode Schistosoma mansoni [J]. Acta Biol Hung, 1992,43:281-286.
[16] Duvaux-Miret O, Capron A. Proopiomelanocortin in helminth Schistosoma mansoni. synthesis ofβ-endorphin, ACTH andα-MSH. existence of POMC-related sequences[J]. Annals of the New York Academy of Sciences, 1992,650:245-250.
[17] Salzet M, Capron A, Stefano GB. Molecurlar crosstalk in host-parasite relationships: schistosome and Leech-host interactions[J]. Parasitol Today, 2000,16:536-540.
[18] Salzet M. Invertebrate molecular neuroimmune processes [J]. Brain Review, 2000,34: 69-79.
[19] Pearce EJ, Sher A. Functional dichotomy in CD4+T cell response to Schistosoma mansoni[J]. Exp Parasitol, 1991,73: 463-472.
[20] Pearce EJ, Caspar P, Grzych JM,et al. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by parasitic helminth Schistosoma mansoni[J]. J Exp Med, 1991,173:159-166.
[21] Duvaux-Miret O, Stefano GB, Smith EM, et al. Immunosup pression in the definitive and intermediate hosts of the human parasite Schistosoma mansoniby release of immunoactive neuropeptides[J]. Proc Natl Acad Sci USA, 1992,89:778-781.
[22] Leung MK, Dissous C, Capron A,et al. Schistosoma mansoni: the presence and potential use of opiate-like substances[J]. Exp Parasitol,1995,81:208-15.
[23] Pryor SC, Elizee R. Evidence of opiates and opiod neuropeptides and their immune effects in parasitic invertebrates representing three phyla: Schistosoma mansoni, Theromyzon tessulatum, Trichinella spiralis[J].Acta Biol Hung, 2000,51:331-341.
[24] Xavier EM, Lucena-Silva N, Werkhauser RP,et al. The tegument of Schistosoma mansoni: genes, antigens and the host-parasite relationship[J]. Mem Inst Oswaldo Cruz, 1998,93(Suppl):85-86.
[25] Abath FG, Werkhauser RC. The tegument ofSchistosoma mansoni: functional and immunological features[J]. Parasit Immunol, 1996,18:15-20.
[26] Brouwers JF, Skelly PJ, Van Golde LM,et al. Studies on phospholipid turn over argue against sloughing of tegument membranes in adult Schistosoma mansoni[J]. Parasitology, 1999,119(pt3):287-294.
[27] Simpson AJG. Schistosome surface antigens: development expression and immunological function[J]. Parasitol Today, 1990,6:40-45.
[28] Mountford AP, Trottein F. Schistosomes in the skin: a balance between immune priming and regulation[J]. Trends in Parasitology, 2004,20(5):221-226.
[29] Francois T, Sophie N, Ve ronique A. Schistosoma mansoni schistosomula reduce E-selectin and VCAM-1 expression in TNF-α-simulated lung Microvascular endothelial cells by interfering with the NF-κB pathway[J].Eur J Immuol,1999, 29(11):3691-3701
[30] Tato C, Hunter C. Host-pathogen Interactions: Subversion and Utilization of the NF-κB Pathway during Infection[J]. Infection and immunity,2002,70(7):3311-3317.
[31] Capron A, Riveau G, Carpron M. Schistosomes: the road from host-parasite interactions to vaccines in clinical trials[J].Trends in Parasitology, 2005,21(3):143-149
[32]李浩.何艳燕,林矫矫,等.东方田鼠抗日本血吸虫现象的观察[J].中国兽医寄生虫病,2000,8(2):12—15.
[33]李浩.何艳燕,林邦发,等.东方田鼠重复感染日本血吸虫试验初步研究[J].中国兽医寄生虫病,2001,9(3):15—17.
[34]朱国正,汪英华,雷观愚,等.东方田鼠的实验室饲养及其抗血吸虫感染特性[J].上海实验动物科学,1991,ll(4):l93—198.
[35]王庆林,易新元,曾宪芳,等.东方田鼠感染日本血吸虫后肺和肝的组织细胞反应及虫体的扫描电镜观察.中国人兽共患病杂志,2002,18(4):65～67.
[36]李浩,何艳燕,林矫矫,等.东方田鼠抗日本血吸虫病现象的观察.中国兽医寄生虫病,2000,8(2):12～15.
[37]王庆林,易新元,曾宪芳,等.东方田鼠感染日本血吸虫后肺和肝的组织细胞反应及虫体的扫描电镜观察.中国人兽共患病杂志,2002,18(4):65～67.
[38] Zhou XN, Chen MG, Don MM, et al. Schistosomiasis control in the 21st century proceedings of the international symposium on schistosomiasis,Shanghai. July 4-6,2001.Acta Tropica, 2002(82): 95～114.
[39]张新跃,何永康,李毅,等.正常东方田鼠血清及脾细胞体外杀血吸虫童虫作用的初步观察[J].中国血吸虫病防治杂志。2001,13(4):206—208.
[40]刘金明,傅志强,李浩,等.东方田鼠血清体外杀伤日本血吸虫童虫效果的初步观察[J].中国人兽共患病杂志,2002,18(2):82—84.
[41] He Y,Luo X,Zhang X,et al. Immunological characteristics of natural resistance in Microtus fortis to infection with Schistosoma japonicum [J].Chin Med J,1999,112(7):649—654
[42]何永康,罗新松,张新跃,等.东方田鼠天然抗血吸虫感染免疫特性的研究.中国血吸虫病防治杂志,1998,10(增刊):73～77.
[43]蒋守富,魏梅雄,林娇娇,等.东方田鼠抗日本血吸虫抗体IgG亚类的初步研究.中国血吸虫病防治杂志,2001,13(1):1～3.
[44]傅志强,刘金明,蒋守富,等.东方田鼠抗日本血吸虫抗体水平监测与分析.中国兽医寄生虫病,2001,9(4):6～8.
[45]张新跃,何永康,李毅,等.正常东方田鼠血清及脾细胞体外杀血吸虫童虫作用的初步观察[J].中国血吸虫病防治杂志。2001,13(4):206—208.
[46]刘金明,傅志强,李浩.东方田鼠ADCC体外杀伤日本血吸虫童虫效果的初步观察[J].寄生虫与医学昆虫学报,2001,8(4):212—219.
[47]罗新松,何永康等,东方田鼠血清被动转移小白鼠抗血吸虫感染的保护性研究[J].中国人兽共患病杂志,1998,14(5): 75-76.
[48] Vignali DA, Bickle QD, Taylor MG, et al. Comparision of the role of complement in immunity to Schistosoma mansoni in rats and mice. Immunology. 1988, 63(1): 55-61.
[49]刘金明,傅志强,李浩,等.东方田鼠血清体外杀伤日本血吸虫童虫效果的初步观察.中国人兽共患病杂志,2002,18(2):82-84.
[50] Widmer MB. Regulation of cytolytic T-lymphocyte generation by B cell stimulatory factor. Nature, 1987, 326:795.
[51] Snapper CM, Finkelman FD, Paul WE. Differential regulation of IgG1 and IgE synthesis by interleukin 4. The Journal of Experimental Medicine, 1988,167:183.
[52]何永康,罗新松,张新跃,等.东方田鼠天然抗血吸虫感染免疫特性的研究.中国血吸虫病防治杂志,1998,10(增刊):73～77.
[53]阎玉涛,刘述先,宋光承,等.东方田鼠天然抗体相关的日本血吸虫抗原基因筛选和克隆.中国寄生虫学与寄生虫病杂志,2001(19):153～156.
[54]张亮,程国锋,傅志强,等.血吸虫新抗原基因SjMF4的克隆、表达及功能分析.生物化学与生物物理学报,2003,35(12):1099～1104.
[55]王庆林,易新元,曾宪芳,等.东方田鼠感染血清免疫筛选日本血吸虫成虫cDNA文库.中国生物化学与分子生物学学报,2001,17(5):547～551.
[56]欧阳理,王庆林,曾宪芳,等.从随机多肽库中筛选日本血吸虫抗原模拟表位诱导保护性免疫的研究.中国热带医学,2002,2(2):132～135.
[57] Shoemaker DD, Schad, A rmour CD, et al. Experimental annotation of the human genome using microarray technology. Nature, 2001; 409 (6822) : 922-927.
[58]安利峰,胜利.基因芯片及其应用进展[J].西北民族学院学报,2002,23:40-42.
[59]马旭.基因芯片技术及其研究现状和应用前景[J].中国医疗器械信息,2002,8(l):4-7.
[60] Jells CL.Defining critical residues in the epitope for HIV-neutralizing monoclonal antibody using phage display and peptide array technologies. Gene ,1993,137910:63-68
[61] Heller RA,Schena M,Chai A et al.Discovery and analysis of inflammatory disease-related genes using cDNA microarrays.Proc Natl Acad Sci USA,1997,94:2150-2155
[62] XZ Wang, J J Lin,XG Feng, Gene expression patterns during development of schistosoma japoncium in mamman host〔J〕.Mol Bio parasitol (under review)
[63] Nisbet A J,Gasse R B. Profiling of gender-specific gene expression for Trichostrongylus vitrinus(Nematoda:Strongylida)by microarray analysis of expressed sequence tag libraries constructed by suppressive-subtractive hybridization〔J〕. Int J Parasitol,2004,34:633 - 643.
[64]季旻珺,苏川等,日本血吸虫感染过程中抑制性因子的表达特征[J].中国人兽共患病杂志,2005,21(5): 379-382
[65] Morimoto M,Zarlenga D,Beard H,et al. Ascaris suum:cDNA microarray analysis of 4th stage larvae(L4)during self-cure from the intestine〔J〕. Exp Parasitol,2003,104(3 - 4):113 - 121.
[66] Deng M,Lancto C A,Abrahamsen M S. Cryptosporidium parvum regulation of human epithelial cell gene expression. International〔J〕. Int J Parasitol,2004,34:73 - 82.
[67] Celis J E,Kruhoffer M,Gromova I,et al. Gene expression profiling:monitoring transcription and translation products using DNA microarrays and proteomics〔J〕. FEBS Lett,2000,480(1):2 - 16.
[68]何毅勋,杨惠中,毛守白.日本血吸虫宿主特异性研究之一:各哺乳动物体内虫体的发育率、分布及存活情况[J].中华医学杂志,1960,46(6):470-475.
[69] Fukuda K,Fujino T,Oguma T et a1.Studies on host specificity in Paragonimus westermani:ultrastructural study of inflammatory reactions to the parasite in rat muscles[J].Int J Parasitol,1993,23(6):757-763.
[70]何毅勋,郁平,郁琪芳。等.不同宿主感染日本血吸虫尾蚴的皮肤组织反应[J].中国奇生虫学与奇生虫病杂志,1989,7(1):15-18.
[71] Kojima S,Yamamoto N,Kanazawa T et a1.Monoclonal IgE—dependent eosinophil cytotoxicity to haptenated schistosomula of Schistosoma japonicum:enhancement of the cytotoxicity and expressaion of Fc receptors for IgE by Nippostrongy brasiliensis infection[J].J Immunol,1985,134(4):2719～2722.
[72]张弘,徐亚雄.嗜酸性粒细胞在日本血吸虫(中国大陆株)感染小鼠体内的作用[J].中国血吸虫病防治杂志,1993,5(2):86～90.
[73] Meeusen ENT and balic A.Do eosinophils have a role in the killing of helminth parasites[J].Parasitol Today,2000,16(3):95～101.
[74] Chitsulo L,Engels D,Montresor A,et a1.The global status of schistosomiasis and its control[J].Acta Trop,2000,77(1):41—51.
[75]贺宏斌,左家铮,周利红,等.东方田鼠实验感染日本血吸虫的研究[J].湖南医学,1992,9(2):65—67.
[76]黎申恺,朱祖林,金壁如,等.1965.东方田鼠对日本血吸虫的不感染性[J].寄生虫学报,2(1):103～105.
[77]刘杰生,容寿铭,陈佩玑,等.几种鼠类人工感染日本血吸虫的实验观察.中国血吸虫病防治杂志,1992,4(6):350～351
[78]李浩,何艳燕,林矫矫,等.东方田鼠抗日本血吸虫病现象的观察[J].中国兽医寄生虫病,2000,8(2):12-15.
[79] V. Tusher, R. Tibshirani, and G. Chu. Significance analysis of microarrays applied to transcriptional responses to ionizing radiation. [J]. Proc. Natl. Acad. Sci. USA,2001., 98:5116–5121,
[80]孙军,林矫矫,程国锋,等.利用基因表达谱芯片研究东方田鼠和小鼠感染日本血吸虫前后基因的差异性表达[J].北京大学学报(自然科学版),2004,40(4):532～537.
[81] Attila L. Szvetko, Ashleigh Jones, An investigation of the C77G and C772T variations within the human protein tyrosine phosphatase receptor type C gene for association with Multiple Sclerosis in an Australian population[J].Brain Research,2003,2 (5):154—158.
[82] Badovinac VP,Tvirnnereim AR,Harry JT.Regulation of antigen specific CD8+ T cell homeostasis by perforin and interferon-β[J].Science,2000,290(5495):1354—1358.
[83] Byungsuk Kwon, Byung-S Youn, Byoung S Kwon. Functions of newly identified members of the tumor necrosis factor receptor/ligand superfamilies in lymphocytes [J].Current Opinion in Immunology, 1999,11,(3): 340-345
[84] Ken B. Reid, Maurice Colomb, Franz Petry. Complement component C1 and the collectins– first-line defense molecules in innate and acquired immunity[J].Trends in Immunology, 2002,23,(3):115-117
[85] Hogarth PM, Hulett MD, Osman N. Fcγreceptor : gene structure and receptor function [J ]. Immunol Res ,1992,11: 217～225.
[86] HIBBS ML , SELVARAJ P, CARPEN O , et al. Mechanisms for regulating expression of membrane isoforms of FcγrIII (CD16) [ J ]. Science,1989, 246:1608 -1611.
[87] Butterworth AE,Dunne DW.Fulford AJ,et al. Human immunity to Schistosoma mansoni:observation On mechanisms and implications for control[J].Immunot Invest.1992,91(5):391-396.
[88] Ph. Berthelot, C. Guglielminotti, A. Fresard, F. Zeni, F. Lucht .Les immunoglobulines en thérapeutique anti-infectieuse [ J ]. Médecine et Maladies Infectieuses, 1998, 28(5): 414-417
[89] Stanislava Stosic-Grujicic, Ivana Stojanovic, Ferdinando Nicoletti .MIF in autoimmunity and novel therapeutic approaches [ J ].Autoimmunity Reviews, 2009, 8, (3):244-249
[90] E. Mamessier, K. Botturi, D. Vervloet, A. Magnan.Lymphocytes T régulateurs, atopie et asthme : un nouveau concept en trois dimensions [ J ].Revue des Maladies Respiratoires, 2005,22, (2), : 305-311.
[91] Matthew J. Cotter, Daniel A. Muruve. Isolation of neutrophils from mouse liver: A novel method to study effector leukocytes during inflammation[ J ].Journal of Immunological Methods, 2006,312 (30) :68-78
[92] Travis R. Wolter, Randall Wong, Suparna A. Sarkar .DNA microarray analysis for the identification of innate immune pathways implicated in virus-induced autoimmune diabetes [ J ].Clinical Immunology, 2004,3 (30) :248-253
[93] LIU W, SPERO D M. Cysteine protease cathepsin S as a key step in antigen presentation[J].Drug News Perspect,2004,17:357-363
[94] Richard J. Riese, Paula R. Wolf, Dieter Br?mme,et al. Essential Role for Cathepsin S in MHC Class II–Associated Invariant Chain Processing and Peptide Loading [J].Immunity, 1996, 4(4), 357-366
[95] Renaud Seigneuric, Maud H.W. Starmans. Impact of supervised gene signatures of early hypoxia on patient survival[J].Radiotherapy and Oncology, 2007,83, (3):374-382 .
[96] Lo CG, Lu TT, Cyster JG. Integrin-dependence of lymphocyte entry into the splenic white pulp [J].J Exp Med, 2003,197(3):353-361
[97] Saule P,Adriaenssens E,Delacre M,et al. Early variations of host thyroxine and interleukin-7 favor Schistosoma mansoni development. [J]. J Parasito1.2002,88(5):849—855
[98] Briggs MH.metabolism of steroid hormones by Schistosomes [J].Biochim Biophys Acta,1972,280:481—485.
[99] Wei Hu, Qing Yan, Da-Kang Shen.Evolutionary and biomedical annotation of schistosoma japonicum complementary DNA resourceNature[J].Genetics,2003,35:139～147
[100]贾人初,孙毅,刘金明,日本血吸虫童虫裂解物对东方田鼠肝脏T7噬菌体展示cDNA文库的筛选及阳性克隆分析[J].生物工程学报2008,24(5):733-739