第一章 免疫学

MedicalImmunology

授课教师：胡雪梅

xue-mei-hu@163.com《医学免疫学》滨州医学院免疫学教研室医学免疫学（MedicalImmunology）研究人体免疫系统（immunesystem）的结构和功能免疫应答（immuneresponse）的规律免疫功能异常与疾病为诊断、预防和治疗免疫相关疾病奠定基础*免疫学的地位：当今生命科学的前沿学科和现代医学的支撑学科之一教学教材(双语)授课教师考试(理论、实验）理论实验学习目的ReferencebooksReviews

TrendsinImmunology /science?

AnnualReviewofImmunology /loi/immunolNatureReviewImmunologyImmunologicalReviews

/links/toc/imrCurrentOpinioninImmunology /science?

ReferenceBooks&JournalsBasicImmunologyCellularandMolecularImmunologyImmunobiologyAnnualReviewofImmunologyScienceNatureTrendsinImmunologyCurrentopinioninImmunologyImmunityJournalofExperimentalMedicineJournalofClinicalInvestigation单位：免疫学教研室办公地点：实验楼A411

免疫学主任办公室实验室地点：实验楼A三层办公电话：6913364IntroductionofImmunologyHistoryofImmunologyResearchandDevelopmentStrategiesofModernImmunologyGeneralIntroductiontotheImmunesystemAntigens(抗原)*免疫接种与抗感染免疫第一章免疫学发展的历史回顾Chapter1

HistoryoftheImmunology*免疫学科学试验与理论研究*免疫学——一个独立学科的诞生VaccinationandimmunityagainstInfectionDiseaseExperimentalandTheoreticalStudiesofImmunologyImmunology---AnIndependentDisciplineCameintoBeingImmunologydevelopedashumanscontinuedfightingagainstinfectiousdiseases(感染性疾病).

霍乱弧菌流感病毒第一节

免疫接种与抗感染免疫VaccinationandimmunityagainstInfectionDisease*人痘苗及其应用(variolationanditsapplication)*牛痘苗的发明(Inventionofcowpoxvaccination)*减毒活疫苗(Live-attenuatedvaccine)Figure1-1Historicalreviewoftheinfluenza(a)Theinfluenzaepidemic(b)

VaccinationofinfluenzainNewYork1918(a)(b)

vaccinationVaccineNothingknownofmicroorganisms*人痘苗及其应用(variolationanditsapplication)接种疫苗vaccinationEdwardJenner1749-1822VaccineNothingknownofmicroorganismsDiscoveredin1796thatcowpox,orvaccinia（牛痘）,inducedprotectionagainsthumansmallpox(天花)*牛痘苗的发明(Inventionofcowpoxvaccination)1796，Jennar:occupationalexposuretocowpoxpreventssmallpox------vaccination/vaccine经验免疫学时期18世纪Theyshouldbevaccinatedfirst.Whydotheynotwanttoplaywithmykids?Figure1-2Vaccinationledtoaworld-wideeradicationofsmallpoxby1979SmallpoxeradicationWorldHealthOrganizationEradicationeffortbegan1966Lastnaturallyacquiredcase1977,SomaliaRobertKoch(1843-1910):infectiousdiseasescausedbymicroorganisms（微生物）；结核杆菌,

1905年NobelPrize

LouisPasteur(1822-1895):

cholera（霍乱）,anthrax（炭疽）rabiesvaccine（狂犬病疫苗）。免疫学作为一门科学诞生在Pasteur的实验室。Experimentalimmunology19世纪中叶Pauster

isolatemicroorganismsandculturebacterialsuccessfullyLouisPasteur

Thechickenwhichwereinjectedwithfowlcholerabacterium(oldculture)survivedfromasubsequentinjectionoffreshcultureofbacteria.

Aginghadweakenedthevirulenceofthepathogen.An

attenuated（减毒）

(weakened)straincouldprotectthechickensagainstthedisease.

Figure1-6KarlLandsteiner(1868～1943):epitope(表位)，20世纪初20世纪上叶奥地利科学家抗原的特异性仅是由抗原分子中的特殊化学基团所决定，这些化学基团称为表位（epitope

）红细胞表型的特异性是由其表面糖蛋白分子末端寡糖结构所定，并根据其不同将红细胞进行ABO分型，提出了同型输血的原则血型之父20世纪上叶Antibodies(抗体)1890年，VonBrhring/Kitasato将白喉抗毒素用于临床，济世成就1901年vonBehring

获得第一届诺贝尔生理学或医学奖*抗体研究的发展(Developmentofantibodyresearch)1.免疫球蛋白（Immunoglobulins)2.单克隆抗体（Monoclonalantibody)Abisglobin

1975年KohlerandMilstein将产生抗体免疫鼠（接受抗原注射）的脾细胞（含抗体产生细胞）与骨髓瘤细胞融合，形成了具有双亲细胞特点的杂交瘤细胞。ElieMetchnikoffCellularTheory: certainwhitebloodcells,whichhetermedphagocytes,wereabletoingest(phagocytose)microorganismsandotherforeignmaterial1883,cell-mediatedimmunity细胞免疫学派的形成1942年Chase等结核菌素的反应是致敏T淋巴细胞，不是Ab1962年切除鸡的腔上囊后仍可移植排斥。俄国科学家Figure1-7FrankMacfarlaneBurnet（1899～1985）1960年获得诺贝尔奖克隆选择学说Clonalselectiontheory(1)Therearevariouslymphocyteclonesinourbody,eachofthembearsauniquetypeofAgreceptorwhichcanrecognizeAgspecifically.(2)TheclonesoflymphocytesthatcanbeinteractedwithcorrespondingAgwillbeselectedandleadtoactivation,proliferation,produceantibodyandspecificmemorycells.---clonalselection(3)Theclonesoflymphocytesthatcanrecognizeself-Agswillbedestroyedorlearntotolerance(forbiddenclones)attheearlystageoftheirdevelopment.----clonaldeletion(Formationofimmunologysub-disciplines)1971年：免疫学作为一独立学科诞生第二章现代免疫学研究及发展策略ResarchandDevelopmentStrategiesofModernImmunology

免疫学的概念、功能与表现

固有免疫及适应性免疫

现代免疫学研究的热点与发展策略（自学)ConceptofImmunityandItsFunctionsandManifestationsInnateImmunityandAdaptiveImmunityHotSpotsinResearchandStrategiesofModernImmunology1.ConceptofImmunity

(p16)1)Historicalconcept----Immunitymeantprotectionagainstfromdisease,usuallyinfectiousdiseases.2)Modernconcept----Immunityreferstotheabilitytorespondtoforeignsubstances,includingmicrobesandmolecules.P390现代免疫是指机体识别和排除抗原性异物的功能

p16ImmuneFuntionsNormalManifestationsAbnormalManifestationsImmunedefenseImmunehomeostasisImmunesurveilanceresistinginvasionofpathogensNeutralizingtoxinsImmunetolerancetoselfcomponentsKillingtransformedcellsControllingpersistenceinfectionHypersensitivityImmunodeficiencydiseasesAutoimmunediseasestumorPersistentviralinfectionImmunefunctionsandMenifestations免疫功能免疫防御：指正常的免疫应答可阻止和清除入侵的病原体及其毒素等，即抗感染免疫的作用。免疫自稳：指机体对自身成分的耐受、对自身衰老和损伤的细胞的清除，通过免疫调节达到维持机体内环境的稳定的功能。免疫监视：免疫系统识别、杀伤并清除体内突变的细胞，防止肿瘤的发生。BonemarrowspleenBCRConstituteoftheimmunesystemMATLCDTCRImmuneorgancentralperpheralImmunocytesImmunemoleculemembrancesecretorythymusBursaoffibriciusLymphnodeSATLinnateadaptiveMHCCKRCAMIgcomplementcytokineTBmonocytesmacrophageDCneutrophilseosinophilsbasophilsMastcellserythrocytesplatelets免疫应答的种类和特点固有免疫InnateimmunityNaturalornativeimmunityNon-specificimmunityCongenitalimmunity适应性免疫

AdaptiveimmunityAcquiredimmunitySpecificimmunity

HOSTDEFENSE=Innate+adaptiveimmunity第二节固有免疫及适应性免疫InnateimmunityandAdaptiveimmunity

固有免疫细胞的识别特点

模式识别受体（patternrecognitionreceptor,PRR病原相关分子模式（pathogenassociatedmolecularpattern，PAMP）3.TypesofImmunityI.InnateImmunity：机体先天具备的免疫防御功能(ornaturalimmunity/non-specificimmunity)

II.AdaptiveImmunity：机体受抗原激发后而获得的免疫能力(oracquiredimmunity/specificimmunity)细胞免疫体液免疫moleculesFigure2-13InfectionofhostepithelialcellsbySalmonellatyphi伤寒沙门菌Salmonellatyphi树突状细胞Dendriticcell（DC）Figure10-1RecognitionandcytolysismechanismsofNKcells(a)Recognitionofnormalselftissuecells;(b)Recognitionandcytolysisofvirus-infectedcells;(c)RecognitionandcytolysisoftargetcellsthatarecoatedwithantibodyNaturalkillercells,NKcells适应性免疫应答adaptiveimmunity识别阶段活化增殖阶段效应阶段InnateimmunityAdaptiveimmunityMannerofacquiringPhaseofeffectImmunememoryCongenital,existwithbornPRRNoAcquiredbyantigenstimmulationafterbirthTCRBCRHaveimmunememorycellsproducedComparisonofinnateimmunityandadaptiveimmunityNoantigenspecificityPromptDevelopsslowly,AntigenspecificityAntigenrecognitionreceptorFeaturesofInnateimmunityRapidresponsetoamicrobe(hours)LackofmemoryFeaturesofAdaptiveimmunitySlowerresponse(days)StrongmemoryresponseMorespecificTransferredSelf-restrictionAcquired(setupafterbirth)summary病原体入侵早期，发挥免疫防御作用慢特异性强免疫记忆、防止再感染QuestionsComparethecharacteristicsofinnateimmunityandadaptiveimmunity.Whatisthenewconceptofimmunity?Pleaseexplainthefunctionsofimmunity?中枢免疫器官（centralimmuneorgan）

组成：胸腺、骨髓 功能：免疫细胞发生、分化、发育和成熟的场所外周免疫器官（peripheralimmuneorgan）

组成：淋巴结、脾、粘膜免疫系统 功能：成熟的Ｔ细胞、Ｂ细胞定居的地方，也是产生免疫应答的部位第三章免疫系统概述Chapter3GeneralIntroductiontotheImmuneSystemSitesofgenerationofallcirculatingbloodcells(各类血细胞和免疫细胞发生的场所)(B分化成熟的场所)*体液免疫应答的场所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:组成：淋巴结、脾、粘膜免疫系统第二节外周免疫器官（peripheralimmuneorgan）LymphnodeSpleen

MucosalAssociatedLymphoidTissue(MALT)

功能：成熟的Ｔ细胞、Ｂ细胞定居的地方，也是产生免疫应答的部位ThesiteswherematureTandBcellsresidence.Thesiteswhereadaptiveimmuneresponsestoforeignantigensareinitiatedanddevelop.数量：500－600个分布：广泛分布于全身非粘膜部位的淋巴通道上I.Lymphnode(LN)淋巴结Structure:CortexLymphoidfollicle

(Thymus-independentarea)Paracoticalarea

(Thymus-dependentarea)medulla

medullacords:

macrophageandplasmacells

medullasinus

Figure1-8part1of2Functionoflymphnode*SitesofmatureTandBresidence*Sitesofimmuneresponseinitiated*Participateinlymphocyterecirculation*FilteranddischargeofantigenLymphaticSystem淋巴系统

脾（spleen）---人体最大的免疫器官动脉周围淋巴鞘红髓白髓初级滤泡中央动脉脾的结构(StructureofSpleen)Functions:1)siteofTandBcellsresidence2)undergoimmuneresponse3)produceIFN,complement4)filtertheblo