浙江大學(xué)研究生免疫學(xué)英文課件1.introduction背景簡(jiǎn)介

IntroductionAdvancedImmunologyMolecularBiologyImmunologyCellBiologyTroikapromotingModernLifeScience:BriefHistoryofImmunology

1.EmpiricalImmunology

2.ScientificImmunology

3.ModernImmunology天花病人局部痂皮磨成粉鼻吸入預(yù)防兒童天花中國(guó)古代“種人痘”（16~17世紀(jì)）1717

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

Fowlcholera1879

Pasteurellamultocida狂犬病疫苗炭疽病疫苗vaccine梅奇尼科夫(Elie,1845-1916,俄國(guó)動(dòng)物學(xué)家、細(xì)菌學(xué)家,曾獲1908年諾貝爾生理學(xué)-醫(yī)學(xué)獎(jiǎng))貝林(Emilvon,1854-1917,德國(guó)細(xì)菌學(xué)家,曾獲1901年諾貝爾生理學(xué)-醫(yī)學(xué)獎(jiǎng))科赫(Robert,1843-1910,德國(guó)細(xì)菌學(xué)家,醫(yī)學(xué)家,結(jié)核菌、霍亂菌發(fā)現(xiàn)者,曾獲1905年諾貝爾生理學(xué)-醫(yī)學(xué)獎(jiǎng))歐立希（PaulEhrlich，1854-1915，德國(guó)免疫學(xué)家，曾獲1908年諾貝爾生理學(xué)-醫(yī)學(xué)獎(jiǎng)）提出體液免疫理論和抗體生成的側(cè)鏈學(xué)說(shuō)發(fā)現(xiàn)細(xì)胞吞噬作用，提出細(xì)胞免疫理論發(fā)現(xiàn)結(jié)核桿菌；提出病原菌致病的概念發(fā)現(xiàn)抗毒素并治愈一名白喉患者*Burnet（1957年）ClonalselectiontheoryTopImmunologist;1960NobelprizewinnerClonalselectiontheoryEachlymphocytebearsasingletypeofreceptorofuniquespecificity.Antigeninteractionleadstolymphocyteactivation.Daughtercellsbearidenticalantigenspecificitytotheparentcell.

20世紀(jì)獲得諾貝爾醫(yī)學(xué)生理學(xué)獎(jiǎng)的免疫學(xué)家

年代 學(xué)者姓名 國(guó)家 獲獎(jiǎng)成就1901 Behring 德國(guó) 發(fā)現(xiàn)抗毒素，開(kāi)創(chuàng)免疫血清療法1905 Koch 德國(guó) 發(fā)現(xiàn)結(jié)核桿菌，發(fā)明診斷結(jié)核病的結(jié)核菌素

1908 Ehrlich 德國(guó) 提出抗體生成側(cè)鏈學(xué)說(shuō)和體液免疫學(xué)說(shuō)

Metchnikoff 俄國(guó) 發(fā)現(xiàn)細(xì)胞吞噬作用，提出細(xì)胞免疫學(xué)說(shuō)1912 Carrel 法國(guó) 器官移植1913 Richet 法國(guó) 發(fā)現(xiàn)過(guò)敏現(xiàn)象1919 Bordet 比利時(shí) 發(fā)現(xiàn)補(bǔ)體,建立補(bǔ)體結(jié)合試驗(yàn)

1930 Landsteiner 奧地利 發(fā)現(xiàn)人紅細(xì)胞血型1951 Theler

南非 發(fā)明黃熱病疫苗1957 Bovet 意大利 抗組胺藥治療超敏反應(yīng)1960 Burnet 澳大利亞 提出抗體生成的克隆選擇學(xué)說(shuō)

Medawar 英國(guó) 發(fā)現(xiàn)獲得性移植免疫耐受性1972 Edelman 美國(guó) 闡明抗體的化學(xué)結(jié)構(gòu)

Porter 英國(guó) 闡明抗體的化學(xué)結(jié)構(gòu)1977 Yalow 美國(guó) 創(chuàng)立放射免疫測(cè)定法1980 Dausset 法國(guó) 發(fā)現(xiàn)人白細(xì)胞抗原

Snell 美國(guó) 發(fā)現(xiàn)小鼠H-2系統(tǒng)

Benacerraf 美國(guó) 發(fā)現(xiàn)免疫應(yīng)答的遺傳控制Jerne 丹麥 提出天然抗體選擇學(xué)說(shuō)和免疫網(wǎng)絡(luò)學(xué)說(shuō)

Kohler 德國(guó) 雜交瘤技術(shù)制備單克隆抗體

Milstein 阿根廷 單克隆抗體技術(shù)及Ig基因表達(dá)的遺傳控制

Tonegawa

日本 抗體多樣性的遺傳基礎(chǔ)

Murray 美國(guó) 第一例腎移植成功

Thomas 美國(guó) 第一例骨髓移植成功1996 Doherty 澳大利亞 提出MHC限制性，即T細(xì)胞的雙識(shí)別模式

Zinkernagel

瑞士 提出MHC限制性，即T細(xì)胞的雙識(shí)別模式潘建平邵傳森主編《醫(yī)學(xué)免疫學(xué)》浙江大學(xué)出版社2006何維主編《醫(yī)學(xué)免疫學(xué)》人民衛(wèi)生出版社2005AbbusAK,etal.CellularandMolecularImmunology.6thed.ElsevierSaunders2007JanewayCA,etal.Immunobiology.7thed.GarlandSciencePublishing2007龔非力主編《醫(yī)學(xué)免疫學(xué)》第二版科學(xué)出版社2004陳蔚峰主編《醫(yī)學(xué)免疫學(xué)》第五版人民衛(wèi)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