第一章 免疫學(xué)

MedicalImmunology

授課教師：胡雪梅

xue-mei-hu@163.com《醫(yī)學(xué)免疫學(xué)》濱州醫(yī)學(xué)院免疫學(xué)教研室醫(yī)學(xué)免疫學(xué)（MedicalImmunology）研究人體免疫系統(tǒng)（immunesystem）的結(jié)構(gòu)和功能免疫應(yīng)答（immuneresponse）的規(guī)律免疫功能異常與疾病為診斷、預(yù)防和治療免疫相關(guān)疾病奠定基礎(chǔ)*免疫學(xué)的地位：當(dāng)今生命科學(xué)的前沿學(xué)科和現(xiàn)代醫(yī)學(xué)的支撐學(xué)科之一教學(xué)教材(雙語(yǔ))授課教師考試(理論、實(shí)驗(yàn)）理論實(shí)驗(yàn)學(xué)習(xí)目的ReferencebooksReviews

TrendsinImmunology /science?

AnnualReviewofImmunology /loi/immunolNatureReviewImmunologyImmunologicalReviews

/links/toc/imrCurrentOpinioninImmunology /science?

ReferenceBooks&JournalsBasicImmunologyCellularandMolecularImmunologyImmunobiologyAnnualReviewofImmunologyScienceNatureTrendsinImmunologyCurrentopinioninImmunologyImmunityJournalofExperimentalMedicineJournalofClinicalInvestigation單位：免疫學(xué)教研室辦公地點(diǎn)：實(shí)驗(yàn)樓A411

免疫學(xué)主任辦公室實(shí)驗(yàn)室地點(diǎn)：實(shí)驗(yàn)樓A三層辦公電話(huà)：6913364IntroductionofImmunologyHistoryofImmunologyResearchandDevelopmentStrategiesofModernImmunologyGeneralIntroductiontotheImmunesystemAntigens(抗原)*免疫接種與抗感染免疫第一章免疫學(xué)發(fā)展的歷史回顧C(jī)hapter1

HistoryoftheImmunology*免疫學(xué)科學(xué)試驗(yàn)與理論研究*免疫學(xué)——一個(gè)獨(dú)立學(xué)科的誕生VaccinationandimmunityagainstInfectionDiseaseExperimentalandTheoreticalStudiesofImmunologyImmunology---AnIndependentDisciplineCameintoBeingImmunologydevelopedashumanscontinuedfightingagainstinfectiousdiseases(感染性疾病).

霍亂弧菌流感病毒第一節(jié)

免疫接種與抗感染免疫VaccinationandimmunityagainstInfectionDisease*人痘苗及其應(yīng)用(variolationanditsapplication)*牛痘苗的發(fā)明(Inventionofcowpoxvaccination)*減毒活疫苗(Live-attenuatedvaccine)Figure1-1Historicalreviewoftheinfluenza(a)Theinfluenzaepidemic(b)

VaccinationofinfluenzainNewYork1918(a)(b)

vaccinationVaccineNothingknownofmicroorganisms*人痘苗及其應(yīng)用(variolationanditsapplication)接種疫苗vaccinationEdwardJenner1749-1822VaccineNothingknownofmicroorganismsDiscoveredin1796thatcowpox,orvaccinia（牛痘）,inducedprotectionagainsthumansmallpox(天花)*牛痘苗的發(fā)明(Inventionofcowpoxvaccination)1796，Jennar:occupationalexposuretocowpoxpreventssmallpox------vaccination/vaccine經(jīng)驗(yàn)免疫學(xué)時(shí)期18世紀(jì)Theyshouldbevaccinatedfirst.Whydotheynotwanttoplaywithmykids?Figure1-2Vaccinationledtoaworld-wideeradicationofsmallpoxby1979SmallpoxeradicationWorldHealthOrganizationEradicationeffortbegan1966Lastnaturallyacquiredcase1977,SomaliaRobertKoch(1843-1910):infectiousdiseasescausedbymicroorganisms（微生物）；結(jié)核桿菌,

1905年NobelPrize

LouisPasteur(1822-1895):

cholera（霍亂）,anthrax（炭疽）rabiesvaccine（狂犬病疫苗）。免疫學(xué)作為一門(mén)科學(xué)誕生在Pasteur的實(shí)驗(yàn)室。Experimentalimmunology19世紀(jì)中葉Pauster

isolatemicroorganismsandculturebacterialsuccessfullyLouisPasteur

Thechickenwhichwereinjectedwithfowlcholerabacterium(oldculture)survivedfromasubsequentinjectionoffreshcultureofbacteria.

Aginghadweakenedthevirulenceofthepathogen.An

attenuated（減毒）

(weakened)straincouldprotectthechickensagainstthedisease.

Figure1-6KarlLandsteiner(1868～1943):epitope(表位)，20世紀(jì)初20世紀(jì)上葉奧地利科學(xué)家抗原的特異性?xún)H是由抗原分子中的特殊化學(xué)基團(tuán)所決定，這些化學(xué)基團(tuán)稱(chēng)為表位（epitope

）紅細(xì)胞表型的特異性是由其表面糖蛋白分子末端寡糖結(jié)構(gòu)所定，并根據(jù)其不同將紅細(xì)胞進(jìn)行ABO分型，提出了同型輸血的原則血型之父20世紀(jì)上葉Antibodies(抗體)1890年，VonBrhring/Kitasato將白喉抗毒素用于臨床，濟(jì)世成就1901年vonBehring

獲得第一屆諾貝爾生理學(xué)或醫(yī)學(xué)獎(jiǎng)*抗體研究的發(fā)展(Developmentofantibodyresearch)1.免疫球蛋白（Immunoglobulins)2.單克隆抗體（Monoclonalantibody)Abisglobin

1975年KohlerandMilstein將產(chǎn)生抗體免疫鼠（接受抗原注射）的脾細(xì)胞（含抗體產(chǎn)生細(xì)胞）與骨髓瘤細(xì)胞融合，形成了具有雙親細(xì)胞特點(diǎn)的雜交瘤細(xì)胞。ElieMetchnikoffCellularTheory: certainwhitebloodcells,whichhetermedphagocytes,wereabletoingest(phagocytose)microorganismsandotherforeignmaterial1883,cell-mediatedimmunity細(xì)胞免疫學(xué)派的形成1942年Chase等結(jié)核菌素的反應(yīng)是致敏T淋巴細(xì)胞，不是Ab1962年切除雞的腔上囊后仍可移植排斥。俄國(guó)科學(xué)家Figure1-7FrankMacfarlaneBurnet（1899～1985）1960年獲得諾貝爾獎(jiǎng)克隆選擇學(xué)說(shuō)Clonalselectiontheory(1)Therearevariouslymphocyteclonesinourbody,eachofthembearsauniquetypeofAgreceptorwhichcanrecognizeAgspecifically.(2)TheclonesoflymphocytesthatcanbeinteractedwithcorrespondingAgwillbeselectedandleadtoactivation,proliferation,produceantibodyandspecificmemorycells.---clonalselection(3)Theclonesoflymphocytesthatcanrecognizeself-Agswillbedestroyedorlearntotolerance(forbiddenclones)attheearlystageoftheirdevelopment.----clonaldeletion(Formationofimmunologysub-disciplines)1971年：免疫學(xué)作為一獨(dú)立學(xué)科誕生第二章現(xiàn)代免疫學(xué)研究及發(fā)展策略ResarchandDevelopmentStrategiesofModernImmunology

免疫學(xué)的概念、功能與表現(xiàn)

固有免疫及適應(yīng)性免疫

現(xiàn)代免疫學(xué)研究的熱點(diǎn)與發(fā)展策略（自學(xué))ConceptofImmunityandItsFunctionsandManifestationsInnateImmunityandAdaptiveImmunityHotSpotsinResearchandStrategiesofModernImmunology1.ConceptofImmunity

(p16)1)Historicalconcept----Immunitymeantprotectionagainstfromdisease,usuallyinfectiousdiseases.2)Modernconcept----Immunityreferstotheabilitytorespondtoforeignsubstances,includingmicrobesandmolecules.P390現(xiàn)代免疫是指機(jī)體識(shí)別和排除抗原性異物的功能

p16ImmuneFuntionsNormalManifestationsAbnormalManifestationsImmunedefenseImmunehomeostasisImmunesurveilanceresistinginvasionofpathogensNeutralizingtoxinsImmunetolerancetoselfcomponentsKillingtransformedcellsControllingpersistenceinfectionHypersensitivityImmunodeficiencydiseasesAutoimmunediseasestumorPersistentviralinfectionImmunefunctionsandMenifestations免疫功能免疫防御：指正常的免疫應(yīng)答可阻止和清除入侵的病原體及其毒素等，即抗感染免疫的作用。免疫自穩(wěn)：指機(jī)體對(duì)自身成分的耐受、對(duì)自身衰老和損傷的細(xì)胞的清除，通過(guò)免疫調(diào)節(jié)達(dá)到維持機(jī)體內(nèi)環(huán)境的穩(wěn)定的功能。免疫監(jiān)視：免疫系統(tǒng)識(shí)別、殺傷并清除體內(nèi)突變的細(xì)胞，防止腫瘤的發(fā)生。BonemarrowspleenBCRConstituteoftheimmunesystemMATLCDTCRImmuneorgancentralperpheralImmunocytesImmunemoleculemembrancesecretorythymusBursaoffibriciusLymphnodeSATLinnateadaptiveMHCCKRCAMIgcomplementcytokineTBmonocytesmacrophageDCneutrophilseosinophilsbasophilsMastcellserythrocytesplatelets免疫應(yīng)答的種類(lèi)和特點(diǎn)固有免疫InnateimmunityNaturalornativeimmunityNon-specificimmunityCongenitalimmunity適應(yīng)性免疫

AdaptiveimmunityAcquiredimmunitySpecificimmunity

HOSTDEFENSE=Innate+adaptiveimmunity第二節(jié)固有免疫及適應(yīng)性免疫InnateimmunityandAdaptiveimmunity

固有免疫細(xì)胞的識(shí)別特點(diǎn)

模式識(shí)別受體（patternrecognitionreceptor,PRR病原相關(guān)分子模式（pathogenassociatedmolecularpattern，PAMP）3.TypesofImmunityI.InnateImmunity：機(jī)體先天具備的免疫防御功能(ornaturalimmunity/non-specificimmunity)

II.AdaptiveImmunity：機(jī)體受抗原激發(fā)后而獲得的免疫能力(oracquiredimmunity/specificimmunity)細(xì)胞免疫體液免疫moleculesFigure2-13InfectionofhostepithelialcellsbySalmonellatyphi傷寒沙門(mén)菌Salmonellatyphi樹(shù)突狀細(xì)胞Dendriticcell（DC）Figure10-1RecognitionandcytolysismechanismsofNKcells(a)Recognitionofnormalselftissuecells;(b)Recognitionandcytolysisofvirus-infectedcells;(c)RecognitionandcytolysisoftargetcellsthatarecoatedwithantibodyNaturalkillercells,NKcells適應(yīng)性免疫應(yīng)答adaptiveimmunity識(shí)別階段活化增殖階段效應(yīng)階段InnateimmunityAdaptiveimmunityMannerofacquiringPhaseofeffectImmunememoryCongenital,existwithbornPRRNoAcquiredbyantigenstimmulationafterbirthTCRBCRHaveimmunememorycellsproducedComparisonofinnateimmunityandadaptiveimmunityNoantigenspecificityPromptDevelopsslowly,AntigenspecificityAntigenrecognitionreceptorFeaturesofInnateimmunityRapidresponsetoamicrobe(hours)LackofmemoryFeaturesofAdaptiveimmunitySlowerresponse(days)StrongmemoryresponseMorespecificTransferredSelf-restrictionAcquired(setupafterbirth)summary病原體入侵早期，發(fā)揮免疫防御作用慢特異性強(qiáng)免疫記憶、防止再感染QuestionsComparethecharacteristicsofinnateimmunityandadaptiveimmunity.Whatisthenewconceptofimmunity?Pleaseexplainthefunctionsofimmunity?中樞免疫器官（centralimmuneorgan）

組成：胸腺、骨髓 功能：免疫細(xì)胞發(fā)生、分化、發(fā)育和成熟的場(chǎng)所外周免疫器官（peripheralimmuneorgan）

組成：淋巴結(jié)、脾、粘膜免疫系統(tǒng) 功能：成熟的Ｔ細(xì)胞、Ｂ細(xì)胞定居的地方，也是產(chǎn)生免疫應(yīng)答的部位第三章免疫系統(tǒng)概述Chapter3GeneralIntroductiontotheImmuneSystemSitesofgenerationofallcirculatingbloodcells(各類(lèi)血細(xì)胞和免疫細(xì)胞發(fā)生的場(chǎng)所)(B分化成熟的場(chǎng)所)*體液免疫應(yīng)答的場(chǎng)所ThefunctionsofbonemarrowSitesofgenerationofallcirculatingbloodcellsandimmunecellsSitesofmaturationofBcellsSitesofsecondaryhumoralimmuneresponseoccurInbirdsBcellsmatureinthebursaofFabricius胸腺（thymus）Thymusstroma

cells,especiallyepithelialcells(nursecells):celltocellinteractioncytokineandthymulin-likemolecules(Thymosin胸腺肽，thymulin-胸腺素，thymopoietin胸腺生成素)producedbythymusepithelialcells:

Topromotetheproliferation,differentiationofthymuscellsExtracellularmatrix:enhancetheinteractionMicro-environmentsofthymus

lymphocytesselectedinthymus

Tcellsareselectedthroughaprocessofthymiceducationbeforebeingreleasedintotheperipherallymphoidorgansasmaturelymphocytespositiveselection(recognizeMHC)negativeselection(noresponsetoself-Ag)

ScanningelectronmicrographofthymusDevelopingTcellThymicstromaFunctionsofthymus:SitesofTcellmaturation

Immuneregulation:cytokinesandthymulin-likemolecules(Thymosin，thymulin-，thymopoietin)Barrierfunction:組成：淋巴結(jié)、脾、粘膜免疫系統(tǒng)第二節(jié)外周免疫器官（peripheralimmuneorgan）LymphnodeSpleen

MucosalAssociatedLymphoidTissue(MALT)

功能：成熟的Ｔ細(xì)胞、Ｂ細(xì)胞定居的地方，也是產(chǎn)生免疫應(yīng)答的部位ThesiteswherematureTandBcellsresidence.Thesiteswhereadaptiveimmuneresponsestoforeignantigensareinitiatedanddevelop.數(shù)量：500－600個(gè)分布：廣泛分布于全身非粘膜部位的淋巴通道上I.Lymphnode(LN)淋巴結(jié)Structure:CortexLymphoidfollicle

(Thymus-independentarea)Paracoticalarea

(Thymus-dependentarea)medulla

medullacords:

macrophageandplasmacells

medullasinus

Figure1-8part1of2Functionoflymphnode*SitesofmatureTandBresidence*Sitesofimmuneresponseinitiated*Participateinlymphocyterecirculation*FilteranddischargeofantigenLymphaticSystem淋巴系統(tǒng)

脾（spleen）---人體最大的免疫器官動(dòng)脈周?chē)馨颓始t髓白髓初級(jí)濾泡中央動(dòng)脈脾的結(jié)構(gòu)(StructureofSpleen)Functions:1)siteofTandBcellsresidence2)undergoimmuneresponse3)produceIFN,complement4)filtertheblo