Chapter2Cellsandorgansoftheimmunesystem•knowtheconceptandcomponentofimmunesystem;•Knowimmuneorgans(componentandfunctioninimmunesystem);•Knowimmunecells(concept,category);•MasterthesurfacemarkersontheTandBcells,andthefunctionandsubsetofTandBcells;•UnderstandthematurationanddistributionoftheTandBcells•Understandtherecirculationoflymphocytes;ImmuneorgansImmunecellsImmunemoleculesBasicComponentsoftheImmuneSystemPeripherallymphoidorganCentrallymphoidorganWherematurationoflymphocytetakesplaceTrapantigenandprovidesitesformaturelymphocytestointeractwiththatantigen.ImmuneorgansSection1Centrallymphoidorgans中央淋巴器官1Bonemarrow2ThymusOrganortissuethatprovidesamicroenvironmentnecessaryforlymphocytesmaturationIBoneMarrow1maturationofimmunecelltakesplace2thesideofB-cellmaturation3.thesideofacquiredimmunitytakesplace2ThymusCortex(皮质):immatureTcells,calledthymocytes.Medulla(髓质):issparselypopulatedwiththymocytes.Function:Secretevarioushormones;Promotethedifferentiationofthymocytes.抗原非依赖性分化抗原依赖性分化二级淋巴器官前体T细胞T细胞免疫缺陷先天性胸腺发育不全(DiGeorge综合症)•Digeoge综合征:•胚胎三、四咽囊发育障碍→先天胸腺发育不良,伴随甲状旁腺、主动脉弓、唇、耳发育不良•细胞水平:T细胞不能成熟(随年龄增长T细胞能在胸腺外成熟)•表现:血中Tcell缺乏,细胞免疫缺陷•症状:易患病毒、真菌感染,•移植物抗宿主反应,•自身免疫病,恶性肿瘤原发性T细胞缺陷症无胸腺的裸鼠是T细胞选择性缺陷的天然动物模型TumorsformedbyRat1cellsSection2Peripherallymphoidorgan3.mucosa-associatedlymphoidsystem2.spleen1.Lymphnodes4.Cutaneous-associatedlymphoidsystemInitiationofimmuneresponse1LymphnodeHEVCortexsinus皮质窦capillarytrabecula小梁afferentlymphaticvesselefferentlymphaticvessel输出淋巴管VeinArteryMedullarysinus髓质窦Germinalcentre生发中心Medulla髓质MedullarycordsCapsule囊RightlymphoticductCervicalnodesThoracicductthoracicductaxillaryCysternachyliParavertebralnodesInguinalnodeslymphaticvesselLymphnodesareencapsulatedstructuresthatarestrategicallyplacedthroughoutthebodytoreceiveandfilterantigensandcellsfromperipheralinterstitialfluidandlymph.Alllymphnodeseventuallydrainintothethoracicductandbacktotheperipheralblood.DrainsintoleftsubclavianveinDrainsintorightsubclavianveinHighendothelialvenule,HEV(高内皮毛细血管后微静脉)HEVarespecializedvenules(小静脉)foundinlymphoidtissues.Lymphocytesmigratefrombloodintolymphoidtissuesbyattachingtoandmigratingacrossthehighendothelialcellsofthevessels.GerminalcentersinsecondarylymphoidtissuesaresitesofintenseBcellproliferation,selection,anddeathduringAbresponses.Germinalcentersformaroundfolliculardendriticcell(滤泡树突状细胞)networkwhenactivatedBcellsmigrateintolymphoidfollicles.*germinalcenter生发中心germinalcenter生发中心:在淋巴小结产生淋巴细胞时,有淋巴母细胞(成淋巴细胞lymphoblast)位于淋巴小结的中央部(称此为原始滤泡primaryfollicle),随着反复分裂而逐渐变小,遂成为淋巴细胞而被推向于淋巴小结的周边部位,这样在活泼的不断产生淋巴细胞的淋巴小结内,由于有处于分裂的淋巴母细胞占据中央部位,所以称此部位为生发中心或淋巴母细胞中心。顶部亮区底部亮区冠状区体细胞高频突变树突状细胞上抗原的阳性选择类型转换外套区2Spleen1.Bloodfiltering2.thesideofimmuneresponse3.theeffectofretentionoflymphocytes动脉周围淋巴鞘白髓边缘区3.MALT•黏膜相关淋巴组织:在各种腔道粘膜下有大量的淋巴组织聚集,称为粘膜相关淋巴组织(MALT);其中最重要的是胃肠道粘膜相关淋巴组织(GALT)和支气管相关淋巴组织(BALT),以及鼻相关淋巴组织(NALT)4.CALT•皮肤相关淋巴组织表皮和真皮层中免疫细胞的总称。包括角质形成细胞、朗格汉斯细胞、表皮内淋巴细胞和皮肤淋巴细胞等,其不仅是免疫应答的激发部位,且是免疫应答的效应部位。1.Appendixofa10yearold2.Appendixfroma36-yearoldmanAsolitary孤立的lymphoidnoduleinthelargeintestine.Thisnoduleislocalizedinthemucosaandsubmucosaoftheintestinalwall.ThIgAsIgABMcellMucosalepitheliumImmuneresponseinintestinallymphsystemMacrophagePlasmacellSection3LymphocyteandlymphocyterecirculationLymphocyterecirculationandhoming1Lymphocyterecirculation从中枢免疫器官向外周免疫器官的转移从淋巴结向血液循环的转移从脾脏向血液循环的转移从散在淋巴组织向血液循环的转移2Homing1.淋巴细胞经淋巴循环及血液循环,运行并再分布于全身各处淋巴器官及淋巴组织中。2.淋巴循环汇集于胸导管,再入上腔静脉,进入血液循环。3.血液循环中的淋巴细胞及各类免疫细胞在毛细血管后微静脉处,穿越高内皮细胞微静脉(high-walledendotheliumofthepost-capillaryvenues,HEV),进入淋巴组织及淋巴器官,再由此入淋巴循环。从而使淋巴循环和血液循环互相沟通,免疫细胞得以畅流全身。Lymphocyterecirculation淋巴细胞经HEV离开血液循环进入淋巴结相应区域内定居,并通过输出淋巴管,胸导管返回血循环,经脾动脉进入脾脏的淋巴细胞穿过血管壁进入白髓区,然后移向脾索,脾血窦,最后经脾静脉返回血循环。淋巴细胞归巢(lymphocytehoming)是淋巴细胞的定向游动,包括淋巴干细胞向中枢淋巴器官归巢,成熟淋巴细胞向外周淋巴器官归巢,淋巴细胞再循环以及淋巴细胞向炎症部位(如皮肤,肠道粘膜和关节滑膜等炎症部位)迁移。其分子基础是淋巴细胞表面称之为淋巴细胞归巢受体(lymphocytehomingreceptor,LHR)与内皮细胞上相应的血管地址素(vascularaddressin)的相互作用。Section4ImmunecellThecellsthatparticipateintheimmuneresponse,includingprogenitor前体mediateinnateandadaptiveimmunityrespectively.SmalllymphocyteBasophil嗜碱性粒细胞RedbloodcellsEosinophil嗜酸性粒细胞LargelymphocyteMonocyte单核细胞Neutrophil中性粒细胞PlateletsImmunecellLymphocytesareaclassofwhitebloodcellsthatbearvariablecellsurfacereceptorsforantigens.Therearetwomainclassesoflymphocytes-BandTcells-whichmediatehumoralandcellularimmunityrespectively.LymphocytesGeneralcharacteristicsoflymphocytesRestBandTlymphocytesaresmall,motile能动的,nonphagocyticcells,whichcannotbedistinguishedmorphologically形态学.Knownassmalllymphocytes,thesecellsareonlyabout6µmindiameter(left),Smalllymphocyteshavedenselypackedchromtin染色小体,feworganellea细胞器(right).Restinglymphocyteshavelittlecytoplasm(细胞质)andcondensednuclearchromatin(浓缩的核小体).Uponactivation,thecellenlargestoformalymphoblast(淋巴集落)andthenproliferatesanddifferentiatesintoanantigen-specificeffectorcell.PCSmalllymphocyte(TorB)6µmlymphoblast(TorB)15µmPlasmacell(B)15µmMemorycell(TorB)CLPNKBTThCTLPCLymphocytesubsets淋巴细胞亚型TCELLSBCELLSCommonLymphoidprecursorTHELPERCELLSCYTOTOXICTCELLSPLASMACELLSActivateBcellsAndmacrophagesKillvirusInfected