特异性B淋巴细胞应答免疫学课件

1 第十七章特异性B淋巴细胞应答 中南大学基础医学院免疫学系田伟博士 教授 ImmunityandtheImmuneResponseSystem HumoralorB CellMediatedImmuneResponse Producessecretedantibodies proteins Bindtoantigensandidentifytheantigencomplexfordestruction EachBlymphocytemakesauniqueantibodymolecule immunoglobulinorIg OveramilliondifferentBlymphocytesareproducedineachindividual ActivationofBLymphocytesandProductionofAntibodies AntibodiesareproducedbyBlymphocytesandtheirprogeny NaiveBlymphocytesrecognizeantigensbutdonotsecreteantibodies Plasmacellssecreteantibody ImmunologicallyNaive NopreviousexperienceNomemory BCellReceptorComplex 第一节B细胞对TD抗原的免疫应答 11 13 活化辅助受体组成 CD19 CD21 CD81CD19胞浆区有9个Tyrosine残基 募集含SH2结构域的信号分子 加强了由BCR复合物传导的信号 明显降低抗原激活B细胞的阈值 从而大大提高了B细胞对抗原刺激的敏感性 14 信号1 BCR直接识别抗原表位 CD19 CD21 CD81为辅助受体 信号2 T细胞B细胞CD40L CD40ICAM 1 2 3 LFA 1细胞因子 IL 4 5 6 B细胞活化所需要的信号 15 Two SignalModelofHumoralImmuneResponse ActivationandMigration ActivatedhelperT cells effectorcells interactwithAg stimulatedB cellsatedgeoffolliclesinlymphoidtissue B CellActivation 20 BCR复合物与T细胞复合物介导的细胞信号转导的差别 GerminalCenters GC Function togenerateBcellsthatproduceantibodieswithincreasedaffinityfortheinducingantigen affinitymaturationGerminalCenterReaction ActivatedBcellsgiverisetoCentroblasts localizeinfollicle undergorapidcelldivisionandturnonmachinerythatcausessomaticmutationinV regionsCentroblastsgiverisetoCentrocytes SeveralimportantmodificationsoccurintheGC somatichypermutation affinitymaturationandisotypeswitching Ki67 FDC CD4T Somatichypermutation AffinityMaturation AffinityofAbproducedtoproteinAgincreaseswithprolongedorrepeatedexposurestothatAgAbbindingtomicrobeorAgincreasesifinfectionispersistentorrecurrentduetopointmutationsintheVregion AgbindinghypervariableregionhappensonlyinT dependentproteinAgmutationrate1 1000nucleotides somatichypermutation AffinityMaturation IsotypeSwitching Heavyclasschainisswitchedtoadifferentisotypetobroadenfunctionalcapabilities HelperT cellhelpwiththeswitchfromIgM IgDtoanotherisotype IsotypeSwitching Needtomakearesponsethatcanremovevariousmicrobes needstobemorethanIgMandIgD ClassswitchingismediatedbyCD40L CD40mediatedsignals differentcytokinesinvolvedcytokinesinfluenceswhichheavychainclassanindividualB cellandprogenywillswitchto WithoutCD40LorCD40 B cellssecreteonlyIgM AbmayhavenewheavychainbutthespecificityinthevariableregionisthesameasIgM VDJregionstaysthesame whereAbspecificityresides IgA plasmacellsingreen IgG plasmacellsinred X linkedHyperIgMsyndrome IgG IgA IgEdeficiency X LinkedHyperIgMSyndrome InactivatingmutationsinCD40LgeneontheX chromosome nofunctioningformsofCD40LMostlyIgMAbproducedduetothedefectiveheavychainswitching 初始T细胞多由树突状细胞活化 记忆T细胞可识别多种APC提成的抗原 再次应答过程中 记忆性B细胞作为APC摄取 处理抗原 并将抗原提呈给记忆性Th细胞 34 根据激活B细胞方式的不同 TI抗原又可分为TI 1抗原和TI 2抗原两类 第二节B细胞对TI抗原的免疫应答 35 TI 1 B细胞表位 B细胞有丝分裂原成分高浓度时 致多细胞克隆活化 低浓度时 只有带Ag特异BCR的B才能活化 无需Th参加成熟或不成熟B细胞均可被TI 1抗原激活 诱导产生低亲和力的IgM 不能形成免疫记忆TI 2 重复B表位 多为细菌胞壁与荚膜多糖 B细胞对TI抗原的免疫应答 使机体在TD抗原免疫应答建立之前 如感染初期 即可产生特异性抗体 针对某些胞外细菌TI 2抗原 如荚膜多糖 的特异性抗体 可促进巨噬细胞对病原体的吞噬 第三节体液免疫应答的一般规律 ThePrimaryImmuneResponse antigenchallenge lag logphase plateau decline antibodytiter time Fourphasesoftheprimaryresponse alagphasewhennoantibodyisdetectedalogphaseinwhichtheantibodytiterriseslogarithmicallyaplateauphaseduringwhichtheantibodytiterstabilizesaphase decline duringwhichtheantibodyisclearedorcatabolized Featuresofprimaryandsecondaryantibodyresponses Primaryandsecondaryantibodyresponsesdifferinseveralrespects Inaprimaryresponse naiveBcellsinperipherallymphoidtissuesareactivatedtoproliferateanddifferentiateintoantibody secretingcellsandmemorycells Someantibody secretingplasmacellsmaymigratetoandsurviveinthebonemarrowforlongperiods Featuresofprimaryandsecondaryantibodyresponses Inasecondaryresponse memoryBcellsareactivatedtoproducelargeramountsofantibodies oftenwithmoreheavychainclassswitchingandaffinitymaturation Manyofthefeaturesofsecondaryresponses e g heavychainisotypeswitching affinitymaturation areseenmainlyinresponsestoproteinantigens becausethesechangesinBcellsarestimulatedbyhelperTcellsandonlyproteinsactivateTcells TheAnamnesticImmuneResponse Time 1 10 100 1000 antibodytiter PrimaryResponse SecondaryResponse 第四节体液免疫应答的效应 Theeffectorfunctionsofantibodies antibodyresponsescanbelong lasting canexistforyearsaftertheinitialencounterorvaccination e g 10yearsfortetanustoxoidvaccination Theprocessofcoatingparticlesforsubsequentphagocytosisiscalledopsonization Thespleencontainslargenumbersofphagocytesandisanimportantsiteofphagocyticclearanceofopsonizedbacteria Antibodiescoatmicrobesandpromotetheiringestionbyphagocytes Antibody DependentCellularCytotoxicity Naturalkiller NK cellsandotherleukocytesmaybindtoantibody coatedcellsanddestroythesecells NKcellsexpressanFcreceptor calledFc RIII CD16 thatbindstoarraysofIgGantibodiesattachedtoacell AsaresultofFc RIII mediatedsignals theNKcellsareactivatedtodischargetheirgranules whichcontainproteinsthatkilltheopsonizedtargets SUMMARY Humoralimmunityismediatedbyantibodies whichbindtoextracellularmicrobesandtheirtoxins whicharetherebyneutralizedortargetedford