醫(yī)學免疫學英文版課件：Introduction

IntroductionIMMUNOLOGY曹雪濤主編《醫(yī)學免疫學》第六版人民衛(wèi)生出版社2013金伯泉主編《醫(yī)學免疫學》第五版人民衛(wèi)生出版社2008龔非力主編《醫(yī)學免疫學》第三版科學出版社2009AbbasAK,etal.CellularandMolecularImmunology.7thed.ElsevierSaunders,2012JanewayCA,etal.Immunobiology.8thed.GarlandSciencePublishing,2012References

ImmunologyisonfrontiersoflifesciencesImmunologyisoneofthemainpillarsfordevelopmentofbasicandclinicalmedicineImmunologyisconnectedtightlywithbiotechnologyanditsindustrializationAnumberofmysteriesareunderexplorationinimmunologyWhystudyImmunology?ImmunologyisadifficultFirst,therearelotsofdetails,andsometimesthesedetailsgetinthewayofunderstandingtheconcepts.Aseconddifficultyinlearningimmunologyisthatthereisanexceptiontoeveryrule.Thethirddifficultyinstudyingimmunologyisthatourknowledgeoftheimmunesystemisstillevolving.IntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyImmunity1.Immunity:referstoallmechanismsusedbythebodyasprotectionagainstenvironmentalagentsthatareforeigntothebody.(torecognizeandeliminateforeignsubstances)2.Agents:microorganisms(viruses,bacteriaetc)andtheirproducts,foods,chemicals,pollen,tumorcells,etc.3.Immunesystem:immunetissuesandorgans,immunecells,immunemoleculesIntroduction4.Immuneresponse:thecoordinatedreactionofthemoleculesandcellsintheimmunesystemtoaforeignagent.Benefits:protectthehostfromdiseasesDamagingeffects:causetissuedamage5.Immunology

isthestudyofthewaysinwhichthebodydefendsitselffrominfectiousagentsandotherforeignsubstancesinitsenvironment.Threefunctionsofimmunesystem:

(1)immunologicdefence(2)immunologicsurveillance(3)immunologichomeostasisTheDangerModel:ARenewed

SenseofSelfPollyMatzingerTheSelf-NonselfModelsTheInfectious-Nonself(INS)ModelTheDangerModelIntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponseImmuneResponseIntroduction

Innateimmuneresponse

naturalimmuneresponse

non-specificimmuneresponse

Adaptiveimmune

response

acquiredimmuneresponse

specificimmuneresponseInnateimmunityItreferstoanyinbornimmunitythatisalreadypresentthefirsttimeapathogenisencountered.Itdoesnotrequirepriorexposureandisnotmodifiedsignificantlybyrepeatedexposurestothepathogenoverthelifeofanindividual.IntroductionInnateimmuneresponse

Physiologicalbarriersskinmucousmembranes

Phagocytosispolymorphonuclearleukocytes(PMN)monocytes/macrophages

Naturalkiller(NK)cell

Complementandacutephaseproteins

IntroductionTheprincipalmechanismsofinnateandadaptiveimmunityInnateimmunitymechanismofrecognitionPathogenassociatedmoleculespatterns(PAMPs）:LPS,DNA,RNA,ProteinDanger-associatedmolecularpatterns(DAMPS):DNA,HSPPatternrecognitionreceptors(PRR):

Toll-likereceptor(TLR),C-lectinrecptor(CLR),RIG-I-Likerecptor(RLR),NOD-likeReceptor(NLR)Toll-likereceptor(TLR)TLRManydifferenttypesofbloodcellsparticipateintheimmuneresponsetomicrobes:Innateimmunecells:“phagocytes”macrophage,neutrophils,dendriticcellsAdaptiveimmunecells:“l(fā)ymphocytes”Tcells,Bcells,APCInnateimmuneresponseIntroduction(Lung)MacrophageAttackingE.coli

InnateimmuneresponseIntroductionMacrophageAttackingE.coliAlthoughinnateimmunitycaneffectivelycombatmanyinfections,microbesthatpathogenicforhumanhaveevolvedtoresistinnateimmunity.Defenseagainsttheseinfectionsarethetaskoftheadaptiveimmuneresponse,andthisiswhydefectsintheadaptiveimmunesystemresultinincreasedsusceptibilitytoinfections.AdaptiveimmuneresponseAdaptiveimmuneresponseTheTcellsandBcellsinthebodyrecognizetheantigenand,inturn,becomeactivated.Theactivatedlymphocytesthenproliferateandcarryouttheirspecificeffectorfunctions.TypesofadaptiveimmunityTwotypesofadaptiveimmunityHumoralimmunity:mediatedbyBcellsanddefenseagainstextracellularmicrobes.Cell-mediatedimmunity:mediatedbyTcellsanddefenseagainstintracellularmicrobes.Cell-mediatedimmunity: Phagocytosis(cellulareating) cytotoxcity(cellularkilling)Humoralimmunity: antibodies:(alsocalledimmunoglobulin)proteinssecretedbyBcellsthatbinddirectlyandspecificallytopathogens.Aplement:groupofserumproteinsthatcandirectlykillpathogens.ImmuneEffectorMechanisms?2005ElsevierTypesofadaptiveimmunity.AdaptiveimmuneresponseIntroduction1.Theactivationoflymphocytes

antigeninteractswithspecificreceptors:Bcell---BCR(Bcellreceptor):membraneIgTcell---TCR(Tcellreceptor),co-stimulatorysignal2.Proliferationanddifferentiationoflymphocytes

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

Bcell----Antibody;Tcell----Th,CTL4.MemorycellsAdaptiveimmuneresponseIntroductionBCR(mIg)TCRαβThetwo-signalrequirementforlymphocyteactivation.Signal1isprovidedbyantigenrecognition.Signal2isprovidedbycomponentsofthemicrobesorsubstancesproducedduringtheinnateimmuneresponse.AdaptiveimmuneresponseIntroduction1.Theactivationoflymphocytes

antigeninteractswithspecificreceptors:Bcell---BCR(Bcellreceptor):membraneIgTcell---TCR(Tcellreceptor),co-stimulatorysignal2.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.MemorycellsDownloadedfrom:StudentConsult(on31May200605:26PM)?2005ElsevierDownloadedfrom:StudentConsult(on31May200605:26PM)?2005ElsevierLinksbetweeninnateandadaptiveimmunityTheinnateandadaptiveimmuneresponseIntroductionCharacteristicsCellsMoleculesInnateimmunityRespondsrapidlyNomemoryNoorlowspecificityPhysicalbarriersPhagocytes(PMNsandmacrophages)NaturalkillercellsHumoralfactorsComplementAcutephaseProteinsCytokinesAdaptiveimmunityRespondsSlowlyMemoryHighlyspecificTcellsBcellsDendriticcellsAntibodiesCytokinesGranzymesIndividualBandTcellspossesstheabilitytomakeaspecificreceptor(eachcellmakesadifferentreceptormolecule)AntigenbindstothecellsurfacereceptorandactivatesthecellProcesstakesseveraldays.Effectorcellsandmemorycellsareproduced.Memorycellscanthusbeactivatedfaster.ClonalselectiontheoryFrankM.BurnetTheclonalselectionhypothesisTheNobelPrizeinPhysiologyorMedicine1987"forhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity"SusumuTonegawa（利川根進）

ThegenesencodingtheantigenreceptorsofTandBcellsareassembledbyDNArearrangementasthesecellsdevelop.AsaresultofV(D)Jrecombination,everyBandTcellsexpressesauniqueversionoftheantigenreceptor.GenerearrangementofIgIntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponseImmuneCellsIntroductionhematopoieticstemcell(HSC)MyeloidprogenitorLymphoidprogenitorGranulocytes(eosinophils,neutrophils,basophils)

Monocytes,macrophagesDendriticcellErythrocyteMegakaryocyteTlymphocyteBlymphocyteNKcellDendriticcellMostbloodcellsacttofightinfection.AdaptiveimmunityInnateimmunityBloodcellslineages.1.Lymphocytes(exceptNKcells)arewhollyresponsibleforthespecificimmunerecognitionofpathogens,sotheyinitiateadaptiveimmuneresponses.2.Lymphocytesarederivedfrombone-marrowstemcells.3.Blymphocytesdevelopinthebonemarrow.Tlymphocytesdevelopinthethymus.IntroductionLymphocytesLymphocytesareextremelyheterogeneousinlineage,functionandphenotypeandarecapableofcomplexbiologicresponsesandactivities.Lymphocytesareoftendistinguishedbysurfaceproteinsthatmaybeidentifiedbypanelsofmonoclonalantibodies.Thestandardnomenclaturefortheseproteinsisthe“CD”(clusterofdifferentiation)numericaldesignation.

BLymphocytes⑴BCR:asurfacereceptor(mIg)specificforaparticularantigen⑵Bcellsplasmacellsantibody(thesamespecificityastheBCR)⑶humoralimmunityIntroductionAgsecrete

BLymphocytesIntroductionTCR:T-cellantigenreceptorTCR+>95%

TCR+1–5%1.CytotoxicTcells(CTL)2.helperTcells:Th1,Th2,Th173.RegulatoryTcells(Treg)andsuppressorTcells(Ts)IntroductionTLymphocytesPropertiesofTH1,TH2,andTH17subsetsofCD4+helperTcells.IntroductionTLymphocytes

TlymphocyteIntroduction

TLymphocytesHumanT-lymphocyteAttackingFibroblastTumorCellsSpecializedcellsthatdisplayantigenstoTcellsandprovidesecondsignal.ProfessionalAPCsincludedendriticcells(DCs),macrophages(M)andBcells.Antigenpresentingcells(APC)Macrophage:powerfulinantigenprocessinganddestruction,butlowinantigenpresentation.Dendriticcells(DC):suchasLangerhanscell(LC),powerfulinantigenprocessingandpresentation.IntroductionAntigenpresentingcellsIntroductionNaturalkillercells(NK)1.10-15%ofbloodlymphocytes,LGL2.expressneitherT-cellnorB-cellantigenreceptorsIntroductionPhagocyticcellsMonocytes(blood)/Macrophages(tissues)

functions:1.removeparticulateantigens2.takeup,processandpresentantigenicpeptidestoTcellsdistribution:KupffercellsinthelivermicroglialcellsinthebrainIntroductionPhagocyticcellsPolymorphonucleargranulocytes

1.neutrophils;basophils;eosinophils2.neutrophilsareshort-livedphagocyticcells

multilobednucleus;10-20m3.neutrophilshavealargearsenalofantibioticproteinsgranules:lysosomes;lactoferrinIntroductionPhagocyticcellsIntroductionPhagocyticcellsIntroductionmonocyteneutrophilPhagocyticcellsIntroductioneosinophilneutrophilPhagocyticcellsIntroduction

neutrophilactivatederythrocyteplateletIntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponseTissuesoftheimmunesystemPrimary(orcentral)lymphoidorgansthebonemarrowthethymusSecondary(orperipheral)lymphoidorgansthespleenlymphnodesCutaneousandmucosalimmunesystemIntroductionGenerativelymphoidorgans:theorgansinwhichTandBlymphocytesmatureandbecomecompetenttorespondtoantigens.Peripherallymphoidorgans:theorgansinwhichadaptiveimmuneresponsestoforeignantigens(suchasmicrobes)areinitiated.Maturationoflymphocytes.Maturelymphocytesleavethegenerativelymphoidorgansandentercirculationandtheperipherallymphoidorgans,wheretheyrespondtoforeignantigensandfromwheretheyrecirculateinthebloodandlymph.

theplaceinwhichproliferationofHSCtakesplacetheplaceinwhichdevelopmentandmaturationofBcellsoccurThelymphoidprogenitorcellsaretransportedbycirculatingbloodtothethymusanddifferentiateintofunctionalTlymphocytesIntroductionBonemarrowThethymus1.

Cells:thymicstromalcells(TSC)epithelialcells,monocytes(macrophage),TDCthymocytesTcell(+)2.Structure:cortex---immaturethymocytesmedulla---maturethymocytesM,TDC3.Function:ItisthesiteofTcellmaturation/selection;

ItdeterminesthespecificityoftheTCRexpressedontheTcellsreleasedtoperiphery

IntroductionThelymphnodeHuman:2-10mmindiameterroundandkidneyshapedConsistsof:cortex(B-cellarea)paracortex(T-cellarea)centralmedulla(B-cellarea)IntroductionThelymphnodeIntroductionDownloadedfrom:StudentConsult(on1June200602:08PM)?2005ElsevierThemorphologyoflymphnodes.Thestructuralorganizationandbloodflowinalymphnode.Lightmicrographshowsacross-sectionofalymphnodewithnumerousfolliclesinthecortex,someofthemcontaingerminalcenters,andthecentralmedulla.

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

theredpulp(B)

2.function:

destroytheAg,agedplatelets

immuneresponseIntroductionThespleenIntroductionThespleenDownloadedfrom:StudentConsult(on1June200602:08PM)?2005ElsevierThemorphologyofthespleen.Asplenicarteriolesurroundedbytheperiarteriolarlymphoidsheath(PALS)andtheattachedfolliclecontainingaprominentgermianlcenter.LightmicrographofasectionshowsanarteriolewiththePALSandasecondaryfollicle.Withintheperipherallymphoidorgans,TcellsandBcellsaresegregatedintodifferentanatomiccompartments.Downloadedfrom:StudentConsult(on31May200605:26PM)?2005ElsevierSegregationofTandBcellsindifferentregionsofperipherallymphoidorgans.Thepathbywhichna?veTandBcellsmigratetodifferentareasofalymphnode.ImmunofluorescenceshowsthattheBcellsandTcellslocateinthefolliclesandintheparafollicularcortex,respectively.Mucosalimmunesystem(MIS)

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

(intraepitheliallymphocytes)Adaptiveimmune(Tcells)4.function:local(mucosal)immunityIntroductionMucosal-associatedlymphoidtissue(MALT)McellsandProductionofIgAMcells:epithelialcellslackingthemicrovilli,havingadeeppocketinthebasolateralplasmamembraneLymphocyterecirculationLymphocytesleavethebloodviahigh-walledendotheliumofthepost-capillaryvenules.Lymphocytetraffickingexposesantigentoalargenumberoflymphocytes.Introduction

LymphocyterecirculationIntroductionRecirculationofTcells.NaiveTcellsmigratefrombloodthroughHEVintotheTcellareasofalymphnode,whereTcellsareactivatedbyantigens.ActivatedTcellsexitthelymphnode,enterbloodstream,andmigratepreferentiallytoperipheraltissuesatsitesofinfectionandinflammation,whereinfectiousmicrobesareeliminated.IntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponseImmunopathology

Hypersensitivity-overactiveimmuneresponseImmunodeficiency-ineffectiveimmuneresponseAutoimmunity-inappropriatereactiontoselfantigensCancerIntroductionConceptofImmunityImmuneResponseImmuneCellsTissuesandOrgansoftheImmuneSystemImmunopathologyBriefhistoryofImmuneResponse

BriefHistoryofImmunology1.EmpiricalImmunology(AD1700-1900)2.ScientificImmunology(1900-1950s)3.ModernImmunology(1960s-Present)DocumentsshowthatasearlyasAD1000,theancientChinesecustomexistedofhavingchildreninhalepowdersmadefromthecrustyskinlesionsofpatientsrecoveringfromsmallpoxEdwardJenner(1749-1823)JennervaccinationAliMaaliWhyCanweeradicatethesmallpox??Noanimalreservoir?Lifelongimmunity?Subclinicalcasesrare?Oneserotype?Effectivevaccine?MajorcommitmentbygovernmentsLouisPasteur

Fowlcholera1879

Pasteurellamultocida狂犬病疫苗炭疽病疫苗ScientificImmunologyTheNobelPrizeinPhysiologyorMedicine1901EmilvonBehring"forhisworkonserumtherapy,especiallyitsapplicationagainstdiphtheria,bywhichhehasopenedanewroadinthedomainofmedicalscienceandtherebyplacedinthehandsofthephysicianavictoriousweaponagainstillnessanddeaths".TheNobelPrizeinPhysiologyorMedicine1905RobertKoch"forhisinvestigationsanddiscoveriesinrelationtotuberculosis".TheNobelPrizeinPhysiologyorMedicine1908IlyaIlyichMech