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抗体种类繁多,你知道原因么?
发布时间:2019-02-25   点击次数:188次

彩搜网RENLEISHENGHUOZAIFUZADUOBIANDEHUANJINGZHONG,MEISHIMEIKEDOUHUIJIECHUDAOGEZHONGGEYANGDEWEISHENGWU,SHOUDAOYIXIELEISIKANGYUANWUZHIDEQINRAO,CONGERSHIJITIZHIBING。WEILEDIYUZHEIXIEWAILAIQINRAO,SHIZISHENDEYIJIXUSHENGCUN,RENTIBIXUXINGCHENGJISHIWAN、JIBAIWANSHENZHIGENGDUOZHONGXIANGYINGDETEYIXINGKANGTIYIDIKANGWAIJIEDEKANGYUANWUZHI,CAINENGMIANZAOQIHAI,BAOHUZIJI。WOMENHUICONGKANGTIDECHANSHENGJIDUOYANGXINGJINXINGQIYUANYINDECHANSHUYUFENXI。


1.抗原的呈递

KANGYUANCHENGDIXIBAO(antigen presenting cell, APC)DEKANGYUANCHENGDIZUOYONGSHIYIGESHEJIKANGYUANSHEQU、CHULIYUCHENGDIDEFUZAGUOCHENG。ZHUYAODEKANGYUANCHENGDIFENZISHIZHUYAOZUZHIXIANGRONGXINGFUHEWU(majorhistocompatibility complex, MHC)。MHCFENWEILIANGGEDALEI:MHC-IHEMHC-II,TAMENCHENGDIDEKANGYUANDANBAILAIYUANBUTONG,JIANGJIEKANGYUANDEFANGSHIBUTONG,JIEHETAIDUANZHANGDUYEBUTONG,KEYIFENBIEJIANGKANGYUANCHENGDIJIXIBAODUXINGTXIBAO (CD8 T cell) HEFUZHUXINGTXIBAO (CD4 T cell) 。JIEHE

XIANYIMHC-IICHENGDIWAIYUANXINGDANBAIWEILIJIANSHUKANGYUANTICHENGGUOCHENG。


彩搜网外源性抗原经APC吞噬或吞饮作用,被摄入胞内形成吞噬体,后者与溶酶体融合形成吞噬溶酶体。抗原在吞噬溶酶体内酸性环境中被蛋白水解酶降解为小分子多肽,其中具有免疫原性的称为抗原肽。内质网中合成的MHC-II类分子进入高尔基体后,由分泌小泡携带,通过与吞噬溶酶体融合,使抗原肽与小泡内MHC-Ⅱ类分子结合形成抗原肽-MHCⅡ类分子复合物。所形成的复合物可能在高尔基复合体参与下被转运到细胞膜表面,被T细胞受体(TCR)识别并呈递给TH细胞[6]。供TCR识别的先决条件是两种细胞的直接接触并相互作用。这种细胞间的相互作用涉及APC与TH表面多种分子。除了TCR特异性地同时识别多肽-MHC-Ⅱ分子的复合物外,某些粘附分子也参与抗原呈递过程。活化的TH细胞可分泌各种细胞因子,用于B细胞、Tc细胞等的激活过程,产生可清除抗原的特异性抗体。


2.B细胞分化及抗体的产生

彩搜网BURULEIDONGWUBXIBAODEFENHUAGUOCHENGZHUYAOKEFENWEIQIANBXIBAO、BUCHENGSHUBXIBAO、CHENGSHUBXIBAO、HUOHUABXIBAOHEJIANGXIBAOWUGEJIEDUAN。QIZHONGQIANBXIBAOHEBUCHENGSHUBXIBAODEFENHUASHIKANGYUANFEIYILAIDE,QIFENHUAGUOCHENGZAIGUSUIZHONGJINXING,BUCHENGSHUBXIBAOKAISHIBIAODAMOJIEHEXINGIgM(mIgM)。KANGYUANYILAIJIEDUANSHIZHICHENGSHUBXIBAO(MOBIAOMIANTONGSHIBIAODAmIgMHEmIgD)ZAIKANGYUANCIJIHOU,ZAIAPCHETHXIBAODEFUZHUXIACHENGWEIHUOHUABXIBAO(mIgZHUJIANJIANGDI,FENMIXINGIgZHUJIANZENGJIA,BINGKEFASHENGIgJIYINZHONGLIANDELEIBIEZHUANHUAN),BINGJIXUFENHUAWEIHECHENGHEFENMIKANGTIDEJIANGXIBAO,FAHUITIYEMIANYIDEGONGNENG,ZHEIGEJIEDUANDEFENHUAZHUYAOSHIZAIWAIZHOUMIANYIQIGUANZHONGJINXINGDE。

彩搜网YINCI,KANGTICUNZAIYUJIZHUIDONGWUDEXUEYEDENGTIYEZHONG,JIQIBXIBAODEXIBAOMOBIAOMIAN,QIZHUYAOGONGNENGSHIYUKANGYUANJIEHEHOU,YOUXIAODIQINGCHUQINRUJITINEIDEWEISHENGWU、JISHENGCHONGDENGYIWU。

 

KANGTISHIJUYOU4TIAODUOTAILIANDEDUICHENGJIEGOU,QIZHONG2TIAOJIAOZHANG、XIANGDUIFENZILIANGJIAODADEXIANGTONGDEZHONGLIAN(HLIAN);2TIAOJIAODUAN、XIANGDUIFENZILIANGJIAOXIAODEXIANGTONGDEQINGLIAN(LLIAN)。LIANJIANYOUERLIUJIANHEFEIGONGJIAJIANLIANJIEXINGCHENGYIGEYOU4TIAODUOTAILIANGOUCHENGDEDANTIFENZI。QINGLIANYOUκHEλLIANGZHONG,ZHONGLIANYOUγ、μ、α、εHEδWUZHONG[7],YIJUZHONGLIANFENXINGBUTONGIgFENWEIIgM、IgG、IgA、IgDHEIgE WULEI。

ZHENGGEKANGTIFENZIKEFENWEIHENGDINGQUHEKEBIANQULIANGBUFEN。ZAIJIDINGDEWUZHONGZHONG,BUTONGKANGTIFENZIDEHENGDINGQUDOUJUYOUXIANGTONGDEHUOJIHUXIANGTONGDEANJISUANXULIE。KEBIANQUWEIYU"Y"DELIANGBEIMODUAN,YECHENGKANGYUANJIEHEPIANDUAN(antigen-binding fragment, Fab),YIGEKANGTIFENZISHANGDELIANGGEKANGYUANJIEHEBUWEISHIXIANGTONGDE;"Y"DEBINGBUCHENGJIEJINGPIANDUAN(crystalline fragment, FC)。


3.免疫球蛋白多样性

KANGTIDEZUCHENGJIWEIFUZA,SHIYOUCHENGQIANSHANGWAN、DUOZHONGDUOYANGDEIgFENZISUOZUCHENG。ZHEIXIEIgFENZIZAIXINGZHUANG、DAXIAO、JIEGOUYIJIANJISUANDEZUCHENGHEPAILIESHANG,JIXIANGSI,YOUYOUCHABIE。


3.1可变区异质性

恒定区的基因可以决定Ig分子的类别和亚类,为造成Ig分子多样性的原因之一,但造成免疫球蛋白分子多样性的主要原因在于可变区的异质性。
彩搜网   在可变区内有一小部分氨基酸残基变化特别强烈,这些氨基酸的残基组成和排列顺序更易发生变异,称高变区。高变区位于分子表面,多由17个氨基酸残基构成,少则只有2~3个。高变区是抗原结合位,与抗原表位互补,又称为互补决定区(complement-determiningregions,CDRs),其氨基酸序列决定了该抗体结合抗原抗原的特异性。重链及轻链各含有三个CDR,在三维空间结构中呈现为环状,分布在抗体分子表面与抗原特异性结合。


3.2 V(D)J重组

彩搜网KANGTIDELLIANYOUC、V、JSANGEJIYINCUBIANMA

HLIANYOUC、V、D、JSIGEJIYINCUBIANMA

RENLEIKONGZHIMIANYIQIUDANBAIHLIANDEJIYINWEIDIANZAIDI14HAORANSETIZHANGBEISHANG,YOUBIANMAKEBIANQUDEVJIYINPIANDUAN(VH)、DJIYINPIANDUAN(DH)、JJIYINPIANDUAN(JH)、CJIYINPIANDUAN(CH)4LEIJIYINPIANDUANZUCHENG,QIZHONGVHYOU45ZHONG、DHYOU23ZHONG、JHYOU6ZHONG、CHYOU9ZHONG。HLIANSHANGDEHENGDINGQUYOUCJIYINPIANDUANKONGZHI,YIBANSHIHENGDINGBUBIANDE;HLIANSHANGDEKEBIANQUYOUVH、DH、JH 3ZHONGJIYINPIANDUANKONGZHI。ZAIJIANGXIBAOCHENGSHUGUOCHENGZHONGZHONGLIANJIYINDEVH、JH、DH 3ZHONGJIYINPIANDUANJIANKEYIFASHENGSUIJIZHONGZU,BUTONGDEZUHEDAOZHICHANSHENGBUTONGJIEGOUDEZHONGLIANJIYIN。

 

GENJUTIXIBAOJIYINZHONGPAIXUESHUO,BXIBAOZAIWANCHENGZHONGLIANKEBIANQUJIYINDEZHONGPAIHOU,KAISHIQINGLIAN(LλLIANHELκLIAN)KEBIANQUJIYINDEZHONGPAI。RENLEIKONGZHILλLIANDEJIYINWEIDIANZAIDI22HAORANSETIZHANGBEISHANG,YOUVλ、JλHECλ 3LEIJIYINPIANDUAN,QIZHONGVλYOU30ZHONG、JλYOU4ZHONG、CλYOU4ZHONG。LλLIANSHANGDEHENGDINGQUYOUCλJIYINPIANDUANKONGZHI,YIBANSHIHENGDINGBUBIAN;LλLIANSHANGDEKEBIANQUYOUVλHEJλ 2ZHONGJIYINPIANDUANKONGZHI。ZAIJIANGXIBAOCHENGSHUGUOCHENGZHONG,LλLIANJIYINDEVλHEJλ 2ZHONGJIYINPIANDUANJIANKEYIFASHENGSUIJIZHONGZU,BUTONGDEZUHECHANSHENGBUTONGJIEGOUDELλLIANJIYIN。RENLEIKONGZHILκLIANDEJIYINWEIDIANZAIDI2HAORANSETIDUANBEISHANG,YOUVκ、Jκ、Cκ 3LEIJIYINPIANDUAN,QIZHONGVκYOU40ZHONG、JκYOU5ZHONG、CκJIN1ZHONG。

彩搜网ZHEIXIEWAIXIANZIZAIZHONGZUMEI(RE)DEZUOYONGXIA,TONGGUODUOZHONGDUOYANGDEZHONGPAI,SUOHECHENGCHUDETAILIAN,HAIYAOZAIJINYIBUJINXINGLHEHLIANZUHE,ZHEIYANGHOUSHENGCHENGDEKANGTIZHONGLEIJIUFEICHANGDUOLE。KANGTIJIYINZHONGPAIFASHENGZAILINBAXIBAOFENHUADESHIHOU。


3.3类别转换

彩搜网YIGEBLINBAXIBAOKELONGZAIFENHUAGUOCHENGDECHUQI,BUCHENGSHUBXIBAOZHIBIAODAmIgMHEmIgD,ZHEILIANGZHONGIgJUYOUXIANGTONGDEKANGYUANJIEHEQUYU。KANGYUANJIHUOBXIBAOHOU,MOSHANGBIAODAHEFENMIDEIgLEIBIEHUICONGIgMZHUANHUANCHENGIgG、IgA、IgEDENGQITALEIBIEHUOYALEIDEIg。CISHIVHJIYINPIANDUANBAOCHIBUBIAN,ERFASHENGCHJIYINJIEDUANDEZHONGPAI,JIJIEHEKANGYUANDETEYIXINGXIANGTONG,DANQIZHONGLIANLEIXING(HENGDINGQU)FASHENGGAIBIAN。ZHEIYANG,TONGYIBXIBAODEZIDAIXIBAOJIUKEYICHANSHENGZHENDUITONGYIKANGYUANDE、TEYIXINGDE、BUTONGLEIBIEDEKANGTI。JUBUWEIHUANJINGHEXIBAOYINZIKEYINGXIANGHEDIAOJIEMIANYIQIUDANBAIDELEIXINGZHUANHUAN。

 

XIBAOYINZIDIAOJIEBXIBAOIgLEIBIEZHUANHUANDEJILIKENENGSHI:(1)CIJIMOUXIEXIBAODEKELONGXUANZEXINGDEZENGZHI,SHIFENMIMOUTEDINGLEI、YALEIKANGTIDEKELONGXIBAOZENGJIA,RUIL-5、IL-6CUJINIgACHANSHENGCHUTONGGUOTONGZHONGXINGZHUANHUANJINXINGDIAOJIEWAI,HAIKEXUANZEXINGCUJINIgADINGXIANGXIBAOFENHUAZENGZHIWEIIgAFENMIXIBAO。(2)TONGGUOYOUDAOTEDINGWEIZHISHANGLIANGGEZHUANHUANQUDEZHONGZU,YOUDAOBXIBAOYOUFENMIIgMXIANGMOUYITONGZHONGXINGIgZHUANHUAN。


3.4体细胞高频突变和抗体的亲和力成熟

BXIBAOZAIWANCHENGZHONGLIANJIYIN、QINGLIANJIYINDEZHONGPAIHOU,CHENGSHUDEBXIBAOZAIWAIZHOULINBAQIGUANSHENGFAZHONGXINJIESHOUKANGYUANCIJIHOUHUIFASHENGGAOPINDUDETUBIAN,ZHUYAOZAIZHONGLIANQUJIYINFASHENGJIANJIDIANTUBIAN,CHENGWEITIXIBAOGAOPINTUBIAN(somatic hypermutation)。TIXIBAODEGAOPINTUBIANJIDAZENGJIALEMIANYIQIUDANBAIJIYINDEDUOYANGXING,TONGSHIHAIKEYISHIXINGCHENGDEKANGTIQINHELIJINYIBUCHENGSHU。

 

彩搜网TUBIANHOUCHANSHENGDEGEZHONGBXIBAOKELONGDEBCRQINHELIGEBUXIANGTONG,ZAIQIBIAOMIANBIAODAGAOQINHELIKANGTIDEBXIBAOHUIZAIYUQITAXIBAODEFANYINGZHONGHUODEQIANGLIEDECUNHUOXINHAO,ERBIAODADIQINHELIKANGTIDEBXIBAOZEZHUJIANDIAOWANG。QIZONGTIJIEGUOSHI,HOUDAIBXIBAOJIQICHANSHENGDEKANGTIDUIKANGYUANDEPINGJUNQINHELIDEDAOLETISHENG,CHENGWEIKANGTIDEQINHELICHENGSHU(affinity maturation),SHISUOFENMIDEKANGTIKEGENGYOUXIAODIBAOHUJITIMIANSHOUWAILAIKANGYUANDEZAICIQINXI。ZHIYOUNEIXIEBIAODAGAOQINHELIKANGYUANSHOUTIDEBXIBAO,CAINENGYOUXIAODEJIEHEKANGYUAN,BINGZAIKANGYUANTEYIDEThXIBAOZENGZHI,CHANSHENGGAOQINHELIKANGTI。

 

ZAIYISHANGDUOYANGXINGKANGTIJIYINZHIDAOXIA,XINGCHENGLEDUOZHONGDUOYANGDEZHONGLIANDANBAIZHIFENZIHEQINGLIANDANBAIZHIFENZI。CIWAI,SHOUTIBIANJI、MIANYIQIUDANBAIDELEIBIEZHUANHUANDENGYINSUYEKEYIDADAZENGJIAMIANYIQIUDANBAIJIEGOUDEDUOYANGXING。KEYISHUO,ZIRANJIEYOUDUOSHAOZHONGKANGYUANWUZHI,RENTIJIUNENGCHANSHENGDUOSHAOZHONGMIANYIQIUDANBAIFENZI,JIUNENGXINGCHENGDUOSHAOZHONGKANGTI。

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