醫(yī)學(xué)免疫學(xué)教學(xué)課件：Chapter 4 Immunoglobulin

Chapter4Immunoglobulin1901vonBering血清治療1908Ehrlich&Metchnikoff抗體生成、吞噬1972Edelman&Poter抗體分子結(jié)構(gòu)1977Yalow放射免疫測(cè)定1984Koler,Milstein&Jerne單克隆抗體1987TonegawaIg基因結(jié)構(gòu)與抗體有關(guān)的諾貝爾獎(jiǎng)獲得者RodneyPorter1917-1985NobelPrizein1972GeraldEdelman1929--NobelPrizein1972SusumuTonegamaNobelPrize1987Thefirstevidencetoshowantibodyisoneofserumproteinfractions1939,A.TiseliusandE.A.KabatToimmunizerabbitswithovalbuminBelongto-globulinfractionimmunoglobulinUntreatedantiserumTreatedantiserum抗體（Antibody,Ab)

是由B細(xì)胞識(shí)別抗原后增殖分化為漿細(xì)胞所產(chǎn)生的一類能與相應(yīng)抗原特異性結(jié)合，具有免疫功能的球蛋白。免疫球蛋白（Immunoglobulin,Ig)：具有抗體活性或化學(xué)結(jié)構(gòu)與抗體相似的球蛋白，亦稱球蛋白。分泌型：存在于體液中，具有抗體的各種功能膜型：B細(xì)胞膜上的抗原受體Ab=Ig,Ig≠Ab；Ab是功能描述，Ig是化學(xué)結(jié)構(gòu)描述；BasicImmunoglobulinStructureHeavy&LightChainsDisulfidebondsInter-chainIntra-chainImmunoglobulinStructure1.重鏈和輕鏈

Ig的兩條長(zhǎng)鏈稱為重鏈（heavyChain，H鏈）分為μ、γ、α、δ、ε兩條輕鏈（lightChain，L鏈）分為κ、λ型。每個(gè)分子的兩條輕鏈完全相同。ImmunoglobulinStructureDomainsVL&CLVH&CH1-CH3 (orCH4)CH1VLCLVHCH2CH3HingeRegionCarbohydrateDisulfidebondImmunoglobulinStructureVariable&ConstantRegionsVL&CLVH&CHHingeRegionCH1VLCLVHCH2CH3HingeRegionCarbohydrateDisulfidebondStructureoftheVariableRegionHypervariableregion(HVR)orcomplementaritydeterminingregions(CDR)Frameworkregions

0102030405060708090100110120130140150160170180190200210220

5040302010

0CDR1CDR2CDR3

抗體分子的多樣性酸殘基的變異率相應(yīng)位置上氨基抗原B細(xì)胞表位抗體CDR表位AbAgIg的水解片段ImmunoglobulinFragments:Structure/FunctionRelationshipsFabAgbindingValence=1SpecifictydeterminedbyVHandVLPapainFcFabFcEffectorfunctionsImmunoglobulinFragments:Structure/FunctionRelationshipsF(ab’)2pFc'PepsinFcPeptidesF(ab’)2Ig的J鏈和分泌片（一）連接鏈（J鏈）由漿細(xì)胞合成的一種糖蛋白。

IgA和IgM含有J鏈（二）分泌片secretorycomponents是分泌型IgA(sIgA）的一個(gè)輔助成分，由粘膜上皮細(xì)胞合成和分泌。保護(hù)sIgA的鉸鏈區(qū)免受蛋白酶的水解破壞介導(dǎo)IgA二聚體的轉(zhuǎn)運(yùn)Ig的其它成分Ig的其它成分a、同種型（isotype)是指同一種屬所有正常個(gè)體Ig分子共同具有的抗原特異性標(biāo)志。同種型決定簇主要存在于Ig恒定區(qū)內(nèi)。IgM(kappa)IgG1(kappa)Ig的抗原性b、同種異型（Allotype)同一種屬不同個(gè)體所產(chǎn)生的同一類型Ig的遺傳標(biāo)記不同，而表現(xiàn)的抗原性差異。IgG1(kappa)Person2IgG1(kappa)Person1c、獨(dú)特型（idiotype)免疫球蛋白V區(qū)所具有的抗原特異性標(biāo)志獨(dú)特型、Ig的超變區(qū)和抗原結(jié)合部位——同一物質(zhì)結(jié)構(gòu)?？躬?dú)特型抗體（抗抗體）IgG1(kappa)Person2anti-BIgG1(kappa)Person1anti-A獨(dú)特型抗原idiotypicantigen

BCR、TCR、IgV區(qū)特異性的氨基酸序列ImmunoglobulinFragments:Structure/FunctionRelationshipsAgBindingComplementBindingSitePlacentalTransferBindingtoFcReceptors抗體抗原結(jié)合所致的分子和細(xì)胞效應(yīng)抗體結(jié)合抗原借助其他分子和細(xì)胞清除抗原由C區(qū)決定必須在結(jié)合抗原以后：暴露分子細(xì)胞的結(jié)合位點(diǎn)Fc受體聚集

Ab的生物學(xué)活性PreventingBacterial

AdherenceToxinNeutralizationVirus-blockingAntibodies通過胎盤和黏膜：IgG所獨(dú)有，是嬰兒獲得天然被動(dòng)免疫的主要原因，主要借助胎盤滋養(yǎng)層細(xì)胞表面的FcR進(jìn)行的?？贵w并非都對(duì)機(jī)體有利

C.HumanImmunoglobulinClassesIgG-Gamma(γ)heavychainsIgM-Muheavy(μ)chainsIgA-Alphaheavy(α)chainsIgD-Deltaheavy(δ)chainsIgE-Epsilonheavy(ε)chains五類Ig的結(jié)構(gòu)IgGPropertiesⅠ4subclassesⅡ

MajorserumIg:IgGaccountsforabout75-80%ofthetotalserumimmunoglobulininnormaladultⅢ

Theabundantantibodyproducedduringsecondary

humoralimmuneresponsesinthebloodⅣ

Placental

transfer–DoesnotrequireAgbinding(except

IgG2)ⅤFixes

complement

(exceptIgG4)ⅥBindstoFcreceptors(exceptIgG2,IgG4)Phagocytes-opsonizationNKcells-ADCC

IgMStructurePentamer(19S)Extradomain(CH4)JchainCH4JChainBCellAntigenReceptor(BcR)Ig-αIg-αIg-βIg-βIgMPropertiesThe

largest，

nohingregionExpressedonthesurfacesofBcells（BCR）First

IgmadebyfetusandBcells（臍帶血IgM升高的意義）ThekeyimmunoglobulinoftheprimaryresponseFixescomplement:anefficientactivatoroftheclassicalcomplementpathway天然的血型抗體、類風(fēng)濕因子是IgMIgAStructureSerum-monomerSecretions(sIgA)Dimer(11S)JchainSecretorycomponentJChainSecretoryPieceIgAPropertiesMajorsecretoryIg(MucosalorLocalImmunity)Tears,saliva,gastricandpulmonarysecretionsneutralizepathogensDoesnotfixcomplement(unlessaggregated)IgDStructureMonomerTailpieceTailPieceIgDPropertiesBcellsurfaceIg(Bcellmaturation)DoesnotbindcomplementIgEStructureMonomerExtradomain(CH4)CH4IgEPropertiesLeastcommonserumIgBindstobasophilsandmastcells(DoesnotrequireAgbinding)Allergic

reactionsParasitic

infectionsBindstoFcreceptoroneosinophilsDoesnotfixcomplement人工制備抗體a.多克隆抗體用抗原免疫動(dòng)物后獲得的免疫血清（抗血清）由不同克隆的B細(xì)胞針對(duì)不同抗原決定簇所產(chǎn)生

針對(duì)不同抗原表位的抗體組成的復(fù)合物b.單克隆抗體一個(gè)B細(xì)胞針對(duì)一個(gè)抗原決定簇所產(chǎn)生雜交瘤技術(shù)制備，1975年骨髓瘤細(xì)胞—無限增殖，脾細(xì)胞－產(chǎn)生抗體，雜交瘤細(xì)胞－大量無限增殖且合成抗體McAb概念：識(shí)別一種抗原表位的B細(xì)胞克隆所產(chǎn)生的均一性抗體