医学免疫学教学课件：Introduction to Immunology

IntroductiontoImmunologyMedicalImmunologyWhatisMedicalImmunology?Immunologyisthestudyofthewaysinwhichthebodydefendsitselffrominfectiousagentsandotherforeignsubstancesinitsenvironment.Immunesystem骨髓脾脏淋巴结胸腺Immunology

-TheBasisofMedicinethephysiologicalfunctioningoftheimmunesysteminstatesofbothhealthanddisease;malfunctionsoftheimmunesysteminimmunologicaldisorders;thephysical,chemicalandphysiologicalcharacteristicsofthecomponentsoftheimmunesystem.ImmunologyMoleclules:Ag,Ig,MHC…

Immunecells:T,B,APC,NK…Immuneresponse:

InnateAdaptive(Cellular,Humoral)Hypersensitivity(Allergy)ImmunetoleranceImmunodeficiencyTumorimmunity…BasicImmunologyClinicalImmunology学科特点1、理论深奥、抽象；2、名词概念的英文缩略语多；3、分子及基因水平的内容多；4、前后知识联系特别紧密；5、是当今生命科学最重要的前沿学科之一。医学免疫学，金伯泉主编，人民卫生出版社，第5版AbbasAK,etal.BasicImmunoloy.3rded.ElsevierSaunders2008AbbasAK,etal.CellularandMolecularImmunology.7thed.ElsevierSaunders2012JanewayCA,etal.Immunobiology.7thed.GarlandSciencePublishing2007ReferencesselfnonselfimmuneresponseimmunetoleranceIntroductionContents:ConceptofImmunityBriefHistoryofImmunologyImmunologicalFunctionsImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyImmunity1.Immunity:referstoallmechanismsusedbythebodyasprotectionagainstenvironmentalsubstancesthatareforeigntothebody.(torecognizeandeliminateforeignsubstances)2.Substances:microorganisms(viruses,bacteriaetc)andtheirproducts,foods,chemicals,pollen,tumorcells,etc.3.Immunesystem:immunetissuesandorgans,immunecells,immunemoleculesIntroduction4.Immuneresponse:istheresponsemadebythehosttodefenditselfagainsttheintroductionofforeignsubstances.benefits;damagingeffects5.Immunology:studythestructureofimmunesystemanditsfunctions.BriefHistoryofImmunology

1.EmpiricalImmunology

2.ScientificImmunology

3.ModernImmunology

1）Thegeneticprincipleofdiversityandspecificityofantibodies

2）GenecloningofTcellreceptor

3）ImmunogeneticsandMHCrestriction

4）Cytokinesandreceptors

5）SignaltransductionWhatdiseasedoesthismanhave?ProgressionofSmallpoxDay7Day3Day5天花病毒(Poxvirus)

祖国医学：扶正祛邪、阴阳理论人痘苗(南宋时期)中国古代有关痘苗文献EdwardJenner(1749-1823)Vaccination(1796)最后一例天花患者阿里毛马林1979年10月26日世界卫生组织宣布消灭天花《备急千金药方》（孙思邈，唐朝581-682）；《肘后备急方》（葛洪，东晋283-363）Cao

X.Immunology

in

China:

the

past,

present

and

future.Nat

Immunol.

2008;9(4):339-42

LouisPasteur

Fowlcholera1879

Pasteurellamultocida……vaccineElie

Metchnikoff(Russia),1845-1916,1908nobelprizeEmilvonBehring(Germany),1854-1917,1901nobelprizeRobertKoch(Germany),1843-1910,1905nobelprizePaulEhrlich(Germany)，1854-1915,1908nobelprizephagocytosis/cellulartheoryfortheinvestigationsconcerningtuberculosis.

fortheworkonserumtherapyespeciallyitsapplicationagainstdiphtheria.

humoraltheory*Burnet（1957）ClonalselectiontheoryTopImmunologist1960NobelprizewinnerModernImmunology1）Thegeneticprincipleofdiversityandspecificityofantibodies

2）GenecloningofTcellreceptor

3）ImmunogeneticsandMHCrestriction

4）Cytokinesandreceptors

5）Signaltransduction……天然免疫识别受体（Toll样受体，TLR）：

BruceA.BeutlerJulesA.Hoffman树突状细胞（DC）：

RalphM.SteinmanImmunologicalFunctionsImmunologicaldefenseImmunologicalsurveillanceImmunologicalhomeostasis

immunetoleranceimmunoregulation免疫系统三大功能的生理和病理表现功能免疫防御免疫稳定免疫监视生理性反应(有利)抵御、清除病原体入侵清除体内衰老、损伤、变性的细胞识别、清除体内突变的细胞病理性反应(有害)超敏反应(过度)

免疫缺陷(不足)自身免疫病(过度)

发生肿瘤(不足)

Xuetao

Cao.ImmunologyinChina:thepast,presentandfuture.

NatImmunol.2008,9:339-342ImmuneResponseIntroduction

Innateimmuneresponse

naturalimmuneresponse

non-specificimmuneresponse

Adaptiveimmune

response

acquiredimmuneresponse

specificimmuneresponseInnateimmuneresponse

Physiologicalbarriersskinmucousmembranes

Phagocytosispolymorphonuclearleukocytes(PMN)monocytes/macrophages

Naturalkiller(NK)cell

Complementandacutephaseproteins

IntroductionInnateimmuneresponseIntroductionMacrophageAttackingE.coliTheNobelPrizeinPhysiologyorMedicine2011朱尔斯·霍夫曼（JulesA.Hoffmann）于1941年生于卢森堡Echternach。他在法国斯特拉斯堡大学学习，于1969年获得博士学位。在德国马尔堡大学从事博士后工作之后，他回到斯特拉斯堡，从1974年到2009年间担任一个研究实验室的负责人。他还担任过斯特拉斯堡分子细胞生物学研究所的主任，并在2007-2008年间担任法国科学院院长。

In1996,histeamreportedthattheTollgene,wasimportantforbattlinginfections.B.

Lemaitreetal.Cell86,973–983;1996布鲁斯·巴特勒（BruceA.Beutler）1957年出生于美国芝加哥。1981年在芝加哥大学获得医学博士学位（MD），之后在纽约的洛克菲勒大学和达拉斯的德克萨斯大学从事科学工作，并发现了LPS（细菌脂多糖）受体。从2000年开始，他成为美国LaJolla市斯科利普斯研究院（TheScrippsResearchInstitute）的遗传与免疫学教授。TheNobelPrizeinPhysiologyorMedicine2011HisteameventuallyfoundLPS-sensinggene,anditlookedremarkablylikeHoffmann'sToll.识别细菌脂多糖（LPS）的受体Toll-likereceptor4A.Poltoraket.al.Science282,2085–2088;1998AdaptiveimmuneresponseTheTcellsandBcellsinthebodyrecognizetheantigenand,inturn,becomeactivated.Theactivatedlymphocytesthenproliferateandcarryouttheirspecificeffectorfunctions.AdaptiveimmuneresponseIntroductionBCR(mIg)TCRαβAdaptiveimmuneresponseIntroduction1.Theactivationoflymphocytes

antigeninteractswithspecificreceptors:Bcell---BCR(Bcellreceptor):membraneIgTcell---TCR(Tcellreceptor)2.Proliferationanddifferentiationoflymphocytes

Bcell----cytokines(IL-4,etc.)Tcell----Antigen-TCR;co-stimulatorysignal;cytokines(IL-2,IL-7,IL-15)3.Effectorcellsandtheirfunctions

Bcell----Antibody;Tcell----CTL,Th4.MemorycellsTheinnateandadaptiveimmuneresponseIntroductionCharacteristicsCellsMoleculesInnateimmunityRespondsrapidlyNomemoryNoorlowspecificityPhysicalbarriersPhagocytes(PMNsandmacrophages)NaturalkillercellsHumoralfactorsComplementAcutephaseProteinsCytokinesAdaptiveimmunityRespondsSlowlyMemoryHighlyspecificTcellsBcellsDendriticcellsAntibodiesCytokinesGranzymesDownloadedfrom:StudentConsult(on31May200605:26PM)©2005ElsevierLinksbetweeninnateandadaptiveimmunityImmuneCellsIntroductionhematopoieticstemcell(HSC)MyeloidprogenitorLymphoidprogenitorGranulocytes(eosinophils,neutrophils,basophils)

Monocytes,macrophagesDendriticcellErythrocyteMegakaryocyteTlymphocyteBlymphocyteNKcellDendriticcell主要的免疫细胞PhagocyticcellsMonocytes(blood)/Macrophages(tissues)

functions:1.removeparticulateantigens2.takeup,processandpresentantigenicpeptidestoTcellsdistribution:KupffercellsinthelivermicroglialcellsinthebrainIntroductionPhagocyticcellsIntroductionmonocyteneutrophilPhagocyticcellsPolymorphonucleargranulocytes

1.neutrophils;basophils;eosinophils2.neutrophilsareshort-livedphagocyticcells

multilobednucleus;10-20

m3.neutrophilshavealargearsenalofantibioticproteinsgranules:lysosomes;lactoferrinIntroductionPhagocyticcellsIntroductioneosinophilneutrophil1.Lymphocytes(exceptNKcells)arewhollyresponsibleforthespecificimmunerecognitionofpathogens,sotheyinitiateadaptiveimmuneresponses.2.Lymphocytesarederivedfrombone-marrowstemcells.3.Blymphocytesdevelopinthebonemarrow.Tlymphocytesdevelopinthethymus.IntroductionLymphocytesLymphocytes(20-40percentofallbloodleukocytes)

BLymphocytes⑴BCR:asurfacereceptor(mIg)specificforaparticularantigen⑵Bcellsplasmacellsantibody(thesamespecificityastheBCR)⑶humoralimmunityIntroductionAgsecreteTCR:T-cellantigenreceptorTCR

+>95%

TCR

+1–5%1.CytotoxicTcells(CTL)2.helperTcells:Th1,Th2,Th33.RegulatoryTcells(Treg)andsuppressorTcells(Ts)IntroductionTLymphocytesIntroductionTLymphocytes

TlymphocyteIntroduction

TLymphocytesHumanT-lymphocyteAttackingFibroblastTumorCellsAntigenpresentingcells(APC)Macrophage:powerfulinantigenprocessinganddestruction,butlowinantigenpresentation.Dendriticcells(DC):suchasLangerhansCell(LC),powerfulinantigenprocessingandpresentation.IntroductionTheNobelPrizeinPhysiologyorMedicine2011拉尔夫·斯坦曼（RalphM.Steinman）【已故】1943年出生于加拿大蒙特利尔，在麦吉尔大学学习生物学和化学。之后在美国哈佛医学院学习医学，1968年获得医学博士学位（MD）。于1970年被纽约洛克菲勒大学接纳，从1988年起成为免疫学教授。担任该校免疫学与免疫性疾病中心主任。

发现树突状细胞Dendriticcells,DC是启动适应性免疫应答的关键细胞R.M.SteinmanandZ.A.Cohn.J.Exp.Med.137,1142–1162;1973

IntroductionNaturalkillercells(NK)1.10-15%ofbloodlymphocytes,LGL2.expressneitherT-cellnorB-cellantigenreceptorsIntroductionTissuesandorgansoftheimmunesystemPrimary(orcentral)lymphoidorgansthebonemarrowthethymusSecondary(orperipheral)lymphoidorgansthespleenlymphnodesMucosal-associatedlymphoidtissue(MALT)IntroductionDownloadedfrom:StudentConsult(on31May200605:26PM)©2005Elsevier

theplaceinwhichproliferationofHSCtakesplacetheplaceinwhichdevelopmentandmaturationofBcellsoccurThelymphoidprogenitorcellsaretransportedbycirculatingbloodtothethymusanddifferentiateintofunctionalTlymphocytesIntroductionBonemarrowThethymus

1.

Cells:thymicstromalcells(TSC)epithelialcells,monocytes(macrophage),TDCthymocytesTcell(

+)2.Structure:cortex---immaturethymocytesmedulla---maturethymocytesM

,TDC3.Function:ItisthesiteofTcellmaturation/selection;

ItdeterminesthespecificityoftheTCRexpressedontheTcellsreleasedtoperiphery

IntroductionThethymusisaprimarylymphoidorganandtheseatofTlymphocytedifferentiationandselection.Itisabi-lobedorganlocatedjustunderthesternumandislargestinpre-puberty.Itinvoluteswithage.ThelymphnodeHuman:2-10mmindiameterroundandkidneyshapedConsistsof:cortex(B-cellarea)paracortex(T-cellarea)centralmedulla(B-cellarea)IntroductionThelymphnodeIntroduction

180-250ggerminalcenter(B)1.thewhitepulpperiarteriallymphaticsheath(T)

theredpulp(B)

2.function:

destroytheAg,agedplatelets

immuneresponseIntroductionThespleenIntroductionThespleenMucosalimmunesystem(MIS)

1.non-encapsulatedlymphoidtissueinthelaminapropriaandsubmucosalareasofthegastrointestinal,respiratoryandgenitourinarytracts.2.tonsil,appendix,Peyer’spatches3.BcellIgAIELAdaptiveimmunity,

Tcell(Intraepitheliallymphocytes)4.function:local(mucosal)immunityIntroductionMucosal-associatedlymphoidtissue(MALT)LymphocyterecirculationLymphocytesleavethebloodviahigh-walledendotheliumofthepost-capillaryvenulesLymphocytetraffickingexposesantigentoalargenumberoflymphocytesIntroduction淋巴细胞再循环

初始T、B淋巴细胞(未接触抗原