浙江大学研究生免疫学英文课件1.introduction背景简介

IntroductionAdvancedImmunologyMolecularBiologyImmunologyCellBiologyTroikapromotingModernLifeScience:BriefHistoryofImmunology

1.EmpiricalImmunology

2.ScientificImmunology

3.ModernImmunology天花病人局部痂皮磨成粉鼻吸入预防儿童天花中国古代“种人痘”（16~17世纪）1717

England:LadyMaryMontagu“Thesmallpox,sofatal,sogeneralamongstus,isentirelyharmlessherebytheinventionofingrafting….IampatriotenoughtobringthisinventionintofashioninEngland.EdwardJenner(1749-1823)Jenner种牛痘图LouisPasteur

Fowlcholera1879

Pasteurellamultocida狂犬病疫苗炭疽病疫苗vaccine梅奇尼科夫(Elie,1845-1916,俄国动物学家、细菌学家,曾获1908年诺贝尔生理学-医学奖)贝林(Emilvon,1854-1917,德国细菌学家,曾获1901年诺贝尔生理学-医学奖)科赫(Robert,1843-1910,德国细菌学家,医学家,结核菌、霍乱菌发现者,曾获1905年诺贝尔生理学-医学奖)欧立希（PaulEhrlich，1854-1915，德国免疫学家，曾获1908年诺贝尔生理学-医学奖）提出体液免疫理论和抗体生成的侧链学说发现细胞吞噬作用，提出细胞免疫理论发现结核杆菌；提出病原菌致病的概念发现抗毒素并治愈一名白喉患者*Burnet（1957年）ClonalselectiontheoryTopImmunologist;1960NobelprizewinnerClonalselectiontheoryEachlymphocytebearsasingletypeofreceptorofuniquespecificity.Antigeninteractionleadstolymphocyteactivation.Daughtercellsbearidenticalantigenspecificitytotheparentcell.

20世纪获得诺贝尔医学生理学奖的免疫学家

年代 学者姓名 国家 获奖成就1901 Behring 德国 发现抗毒素，开创免疫血清疗法1905 Koch 德国 发现结核杆菌，发明诊断结核病的结核菌素

1908 Ehrlich 德国 提出抗体生成侧链学说和体液免疫学说

Metchnikoff 俄国 发现细胞吞噬作用，提出细胞免疫学说1912 Carrel 法国 器官移植1913 Richet 法国 发现过敏现象1919 Bordet 比利时 发现补体,建立补体结合试验

1930 Landsteiner 奥地利 发现人红细胞血型1951 Theler

南非 发明黄热病疫苗1957 Bovet 意大利 抗组胺药治疗超敏反应1960 Burnet 澳大利亚 提出抗体生成的克隆选择学说

Medawar 英国 发现获得性移植免疫耐受性1972 Edelman 美国 阐明抗体的化学结构

Porter 英国 阐明抗体的化学结构1977 Yalow 美国 创立放射免疫测定法1980 Dausset 法国 发现人白细胞抗原

Snell 美国 发现小鼠H-2系统

Benacerraf 美国 发现免疫应答的遗传控制Jerne 丹麦 提出天然抗体选择学说和免疫网络学说

Kohler 德国 杂交瘤技术制备单克隆抗体

Milstein 阿根廷 单克隆抗体技术及Ig基因表达的遗传控制

Tonegawa

日本 抗体多样性的遗传基础

Murray 美国 第一例肾移植成功

Thomas 美国 第一例骨髓移植成功1996 Doherty 澳大利亚 提出MHC限制性，即T细胞的双识别模式

Zinkernagel

瑞士 提出MHC限制性，即T细胞的双识别模式潘建平邵传森主编《医学免疫学》浙江大学出版社2006何维主编《医学免疫学》人民卫生出版社2005AbbusAK,etal.CellularandMolecularImmunology.6thed.ElsevierSaunders2007JanewayCA,etal.Immunobiology.7thed.GarlandSciencePublishing2007龚非力主编《医学免疫学》第二版科学出版社2004陈蔚峰主编《医学免疫学》第五版人民卫生出版社2008ReferencesContents：ConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyImmunity1.Immunity:referstoallmechanismsusedbythebodyasprotectionagainstenvironmentalagentsthatareforeigntothebody.

(torecognizeandeliminateforeignsubstances)2.Agents:microorganisms(viruses,bacteriaetc)andtheirproducts,foods,chemicals,pollen,tumorcells,etc.3.Immunesystem:immunetissuesandorgans,immunecells,immunemolecules4.Immuneresponse:

collectiveandcoordinatedresponsetotheintroductionofforeignsubstances.benefits;damagingeffects5.Immunology:

studythestructureofimmunesystemanditsfunctions.ImmuneResponseIntroduction

Innateimmuneresponse

naturalimmuneresponse

non-specificimmuneresponse

Adaptiveimmune

response

acquiredimmuneresponse

specificimmuneresponseInnateimmuneresponse

Physiologicalbarriersskinmucousmembranes

Phagocytosis

polymorphonuclearleukocytes(PMN)

monocytes/macrophages

Naturalkiller(NK)cell

Complementandacutephaseproteins

IntroductionInnateimmuneresponseIntroduction(Lung)MacrophageAttackingE.coli

AdaptiveimmuneresponseTheTcellsandBcellsinthebodyrecognizetheantigenand,inturn,becomeactivated.Theactivatedlymphocytesthenproliferateandcarryouttheirspecificeffectorfunctions.AdaptiveimmuneresponseIntroduction1.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(PMNs

andmacrophages)NaturalkillercellsHumoralfactorsComplementAcutephaseProteinsCytokinesAdaptiveimmunityRespondsSlowlyMemoryHighlyspecificTcellsBcellsDendriticcellsAntibodiesCytokinesGranzymesDownloadedfrom:StudentConsult(on31May200605:26PM)©2005ElsevierLinksbetweeninnateandadaptiveimmunityImmuneCellsIntroductionhematopoieticstemcell(HSC)MyeloidprogenitorLymphoidprogenitorGranulocytes(eosinophils,neutrophils,basophils)

Monocytes,macrophagesDendriticcellErythrocyteMegakaryocyteTlymphocyteBlymphocyteNKcellDendriticcellIntroductionImmuneCells1.Lymphocytes(exceptNKcells)arewhollyresponsibleforthespecificimmunerecognitionofpathogens,sotheyinitiateadaptiveimmuneresponses.2.Lymphocytesarederivedfrombone-marrowstemcells.3.Blymphocytesdevelopinthebonemarrow.Tlymphocytesdevelopinthethymus.IntroductionLymphocytesBLymphocytes⑴BCR:asurfacereceptor(mIg)specificforaparticularantigen⑵Bcellsplasmacellsantibody(thesamespecificityastheBCR)⑶humoralimmunityIntroductionAgsecreteTCR:T-cellantigenreceptorTCR

+>95%

TCR

+1–5%1.CytotoxicTcells(CTL)2.helperTcells:Th0,Th1,Th2,Th3,Th173.RegulatoryTcells(Treg)andsuppressorTcells(Ts)IntroductionTLymphocytesIntroductionTLymphocytesHumanT-lymphocyteAttackingFibroblastTumorCellsAntigenpresentingcells(APC)Dendriticcells(DC):powerfulinantigenprocessingandpresentation.Macrophage:powerfulinantigenprocessinganddestruction,butlowinantigenpresentation.IntroductionAntigenpresentingcellsIntroductionNaturalkillercells(NK)1.5-10%ofbloodlymphocytes,LGL2.expressneitherT-cellnorB-cellantigenreceptorsIntroductionPhagocyticcellsMonocytes(blood)/Macrophages(tissues)

functions:1.removeparticulateantigens2.takeup,processandpresentantigenicpeptidestoTcellsdistribution:Kupffercellsintheliver

microglialcellsinthebrainIntroductionPhagocyticcellsIntroductionmonocyteneutrophilPhagocyticcellsPolymorphonucleargranulocytes

1.neutrophils;basophils;eosinophils2.neutrophilsareshort-livedphagocyticcells

multilobednucleus;10-20

m3.neutrophilshavealargearsenalofantibioticproteinsgranules:lysosomes;lactoferrin

IntroductionPhagocyticcellsIntroductioneosinophilneutrophilTissuesandorgansoftheimmunesystemPrimary(orcentral)lymphoidorgansbonemarrowthymusSecondary(orperipheral)lymphoidorgansspleenlymphnodesMucosal-associatedlymphoidtissue(MALT)Introduction

TheplaceinwhichproliferationofHSCtakesplaceTheplaceinwhichdevelopmentandmaturationofBcellsoccur.ThelymphoidprogenitorcellsaretransportedbycirculatingbloodtothethymusanddifferentiateintofunctionalTlymphocytes.IntroductionBonemarrowThethymus1.

Cells:thymic

stromalcells(TSC)epithelialcells,monocytes(macrophage),TDC

thymocytesTcell(

+)2.Structure:cortex---immaturethymocytes

medulla---maturethymocytesM

,TDC3.Function:thesiteofTcellmaturation/selection;

ItdeterminesthespecificityoftheTCRexpressedontheTcellsreleasedtoperiphery.IntroductionThelymphnodeHuman:2-10mmindiameterRoundandkidneyshapedConsistsof:cortex(B-cellarea)

paracortex(T-cellarea)centralmedulla(B-cellarea)Introduction