抗原免疫原和其识别.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,获得性免疫,(,Acquired Immunity),适应性免疫,(,Adaptive Immunity),特异性免疫,(,Specific Immunity),固有免疫,(,Innate Immunity),先天免疫,(,Native Immunity),非特异性免疫,(,Nonspecific Immunity),种系发育，进化形成,生来具备，应答迅速,非特异性抗感染免疫,也参与特异性免疫,固有免疫应答和适应性免疫应答的比较,固有免疫应答 适应性免疫应答,长期进化中逐渐形成 抗原激发,种系共有，可遗传 个体特有，不可遗传,无免疫记忆、作用时间短 有免疫记忆、作用时间长,粘膜和上皮细胞、吞噬细胞、,NK T,细胞、,B,细胞、,APC,gd,T,细胞、,B,1 B,细胞,不针对特定抗原（反应广泛）针对特定抗原（反应特异性）,作用迅速、范围广泛 抗原识别、增殖分化、效应阶段,免疫（,Immunity,）,固有免疫（,Innate immunity,）,适应性免疫（,Adaptive immunity,）,抗原,/,免疫原的概念,免疫原（,Immunogen,）,-,启动免疫应答的物质,抗原（,antigen,Ag,）,-,启动适应性免疫应答的物质,固有免疫原（,Innagen,，,Ing,）,-,启动固有免疫应答的物质,固有免疫识别的效应,产生活性氧、活性氮、抗菌肽,细胞因子、粘附分子、急性期蛋白,共刺激分子（,B7.1,、,B7.2),PAMP,、,DAMP,启动、激发以炎症反应为主,的免疫应答，清除病原体和凋亡细胞,固有免疫识别的效应,Ag,启动、激发以特异性,CTL,和,Ab,为主,的免疫应答，清除病原体和靶细胞,产生致敏的淋巴,T,细胞和,Ab,适应性免疫识别的效应,适应性免疫识别的效应,Immunogen,Innagen(INg)/Innate Molecular Pattern(IMP),Antigen(Ag),PAMP,DAMP,Others?,Immunogenicity,Reactigenicity,熊思东,.,道亦道,非故道,-,试论固有免疫中的抗原和,免疫原的定义,.,现代免疫学,2007,27(6):441-443,抗原,/,免疫原的概念,抗原的特性,免疫原性（,immunogenicity,）,抗原性（,antigenicity,）,Ag,T,B,T,浆细胞,致敏,T,细胞,抗体,免疫原性,(immunogenecity),指抗原分子能够刺激机体产生免疫应,答,(,产生特异性抗体及免疫效应细胞,),的性质。,Ag,T,B,T,浆细胞,致敏,T,细胞,抗原性,指抗原分子与免疫应答产物,(,抗体或免疫,效应细胞,),发生特异性结合的性质。,抗原性,(antigenicity),antigenicity,immuogenicity,T,T,T,Ag,免疫原的特点,固有免疫原,抗 原,不限于特定类别的成分或单一分子,启动、诱导固有免疫应答,免疫原性、免疫反应性分离,免疫原性、免疫反应性一致,启动、诱导适应性免疫应答,以表位为识别基础,就免疫应答始动因素而言,异物性是抗原免疫原性的本质。,非己就是异物，抗原来源与宿主的关系越远，异物越强,免疫原性也越强。,抗原的异物性,抗原特异性,概念,-,指某一抗原分子只能诱导相应淋巴细胞发生免,疫应答的专一性，以及只能与相应抗体或效应,细胞特异性结合的专一性。,意义,-,是免疫学诊断与防治的理论依据,(1),两对半：检测,HBV,(2),接种牛痘：消灭天花,决定抗原,特异性的物质基础,表位,T,细胞抗原受体及其识别抗原的特点,MHC,与,peptides,只识别表达于细胞表面非己,MHC,或与自身,MHC,分子结合,成复合物的多肽,只识别氨基酸一级序列的多肽线性决定簇,TCR,识别抗原肽受到自身,MHC,的限制,CD4,+,T,只识别与,MHC-II,分子结合的肽段,CD8,+,T,只识别与,MHC-I,分子结合的肽段,只有,A,图中,TCR,可识别,APC,所递呈的抗原，形成,TCR-,抗原肽三分子复合体,产生,TH,细胞活化的第一信号,Primary activation of,na,ve,T cells requires two independent signals,signal 1:,specific but weak,interaction between,MHC:peptide complex and,TCR/CD4 or TCR/CD8,signal 2,(co-stimulator),interactions between:,B7 and CD28(required),adhesion molecules,(optional,increase contact),O =C -C H,2,-C H,2,Antigen,C H,2,-O H,CH,2,-CH,2,-NH,3,+,C -C H,2,-C H,2,=,O,-,O,CH,2,CH,2,-CH,2,CH,2,CH,2,-CH,2,CH,2,CH,2,-CH,2,-CH2,CH,2,CH,2,-CH,2,CH,2,CH,2,-C,=,O,-,O,+,H,3,N -C H,2,Ionic bond,van der Waals interactions,Hydrophobic interactions,Hydrogen bond,Ionic bond,Antibody,Resting B cell,Crosslinked B cell,Antigen,B-cell,membrane,Ig-/,Cytoplasm,ITAM,Fyn,Blk,Lck,ITAM sequence,Src Syk,Kinases,固有免疫的分子识别,一般概念,PRRs,PAMPs,天然免疫分子识别的机制,一般概念,固有免疫机制存在对,“,异己,”,的分子识别,分子识别可区分,“,有害,”,和,“,无害,”,物质,分子识别依赖多种受体和细胞膜分子,分子识别并非针对某一特点的抗原,bacterium,sig1,(stimulation),1959,original SNS model:,lymphocytes are activated by recognition of foreign things.,B cell,Sir FM Burnet,(1899-1985),Cohn M,Mitchison NA,Paul WE et al.,Reflections on the clonal-selection theory.Nat Rev Immunol.2007,7:823-30.,Clonal selection,The Self-Nonself Model,Burnets original model,each lymphocyte expresss mutiple copies of a single surface receptor specific for a foreign entity.,signaling through this surface receptor initiates the immune response.,the self-reactive lymphocytes are deleted early in life,1969 Bretscher&Cohn,B cells die when they see antigen(signal one)unless rescued by help(signal two),sig1,B cell,T cell,sig1,(stimulation),Two signal model,Costimulation,Sig2,(co-stimulation),1975 Lafferty&Cunningham,T helper cells die when they see antigen unless rescued by co-stimulation(signal two)from APCs.,bacterium,PRRs,1989 Janeway,APCs do not co-stimulate unless activated via PRRs(receptors for evolutionarily distant infectious non-self)PRRs-PAMPs,C.A.Janeway,Jr.,M.D.,The Infectious-Nonself Model,(1943-2003,),APCs are activated by danger/alarm signals from injured cells,such as those exposed to pathogens,toxins,mechanical damage,and so forth,The Danger model,Polly Matzinger,1994 Polly Matzinger,APCs are activated by endogenous cellular alarm signals from distressed or injured cells,Distressed cell,Normal cell,Steinman RM,Cohn ZA.,Identification of a novel cell type in peripheral lymphoid,organs of mice.I.Morphology,quantitation,tissue distribution.,J Exp Med.1973,May 1;137(5):1142-62.,Steinman RM,Cohn ZA.,Identification of a novel cell type in peripheral lymphoid,organs of mice.II.Functional properties in vitro.,J Exp Med.1974 Feb 1;139(2):,380-97.,Steinman RM,Lustig DS,Cohn ZA.,Identification of a novel cell type in peripheral,lymphoid organs of mice.3.Functional properties in vivo.,J Exp Med.1974 Jun 1;,139(6):1431-45.,Steinman RM,Adams JC,Cohn ZA.,Identification of a novel cell type in peripheral,lymphoid organs of mice.IV.Identification and distribution in mouse spleen.,J Exp Med.1975 Apr 1;141(4):804-20.,Steinman RM,Kaplan G,Witmer MD,Cohn ZA.,Identification of a novel cell type,in peripheral lymphoid organs of mice.V.Purification of spleen dendritic cells,new,surface markers,and maintenance in vitro.,J Exp Med.1979 Jan 1;149(1):1-16.,DC,的发现,www.rockefeller.edu/research/abstract.php?id=150,Ralph M Steinman.Dendritic cells:versatile controllers of the immune system.,Nature Medicine,2007,13,1155-1159,steinmarockefeller.edu,Ralph M Steinman,Cohn ZA and Ralph M Steinman,Cohn ZA and Ralph M Steinman,Michel Nussenzweig,Kayo Inaba and Wesley van Voorhis,www.ascb.org/files/0801profile.pdf,固有免疫识别受体及其配体,模式识别受体及其配体,自身抗原识别受体及其配体,模式识别受体（,Pattern recognition receptors,PRRs,）,分泌型受体,MBL,LBP,sCD14,细胞表面受体,CD14,TLR(,Toll-like receptors,，,TLRs),PGRP,（昆虫细胞）,巨噬细胞甘露糖受体,巨噬细胞清道夫受体,细胞内受体,NODs,（,nucleotide-binding oligomerization domain,，,NODs,）,Mannan-binding lectin forms a complex with serine proteases,LRR domain,（,leucine-rich repeat,）,Cysteine rich domain,TIR domain,1921,年,Little&Snake,研究肿瘤时，发现移植排斥抗原,B,系小鼠肿瘤过继与,A,系小鼠，肿瘤发生排斥。,H-1,、,H-2,、,H-3,多基因决定移植排斥。,小鼠,MHC=H-2,人,MHC=HLA,Jean Dausset,1916-,Nobel Prize 1980,在研究抗原免疫反应时，发现,MHC,基因可控制免疫反应，称为免疫反应基因,(Ir),。,1974,，,Peter Doherty and Rolf Zinkernagle,MHC,限制性,Dr.Zinkernagel Visited Department of Immunology,Fudan University in 2005,淋巴细胞脉络丛脑膜炎病毒,阳性选择获得,MHC,限制性,The world is very dangerous,抗原识别的重要性及意义,TCR,抗原肽,MHC-II,T,细胞,APC,细胞,MHC分子与抗原肽的相互作用,“,识 别,”,才 是 硬 道 理,!,Antibody,TCR,MHC,HIV peptide,How is the pathogen recognized?,感谢上帝赐予免疫系统！,School of Medicine,Fudan University,Thank you!,