免疫学课件-抗感染免疫

Anti-InfectionImmunity

抗感染免疫OutlineMechanismofspecificimmunityandnon-specificimmunityAntibacterialimmunityAntiviralimmunity

Nonspecificimmunity

Specificimmunity

(Innateimmunity)(Acquiredimmunity)SpecificImmunityInnateImmunitySpecificImmunityInnateImmunity&AcquiredimmunityNon-specificimmunitySpecificimmunity

notantigenspecificHeritableImmediateresponse

Exposuredoesnotresultininductionofmemorycells

AntigenspecificNon-heritableAlagtimebetweenexposureandmaximalresponse

ExposureresultininductionofmemorycellsNonspecificImmunityBarrierstructureMacrophageSkinandmucosaBarrier(antibacterialeffectsofnormalflora)BloodBrainBarrierPlacentalBarrier

NeutrophilMononuclearphagocytesystemAnti-bacterialsubstanceinserumandbodyfluidComplementsCytokinesLysozymeInterferonNaturalKillerCellSpecificImmunityHumoralImmunityCellImmunityMucosalimmunesystem(MIS)

Mechanismofanti-infectionimmunityUseothermicrobesasguard-dogsthatkillintruders

Thesearelistedfirstbecausetheyareontheoutsideofthebody,andthusformthefirstlineofdefense.MicrobesPhagocytosis•phagocytes*neutrophil*mononuclearphagocytesystem•processandmechanism•outcome*completephagocytosis*incompletephagocytosis*tissuedamageNeutrophilMonocyteMarcrophages中性粒细胞吞噬脑膜炎奈瑟菌StepOne:ChemotaxiscapillarybloodvesselphagocyteendotheliumbasementmembranePAVEMENTINGDIAPEDESISCHEMOTAXISC5aSiteofinflammation,tissuedamageandimmunereactionsC567C3aStepTwo:ContactStepThree:Phagocytosis/PinocytosisStepFour:Digest&DissolutionOxygenDependentROI&RNIMyeloperoxidase,MPOOxygenIndependentAcidLysosomeandotherenzymesNK细胞

自然杀伤细胞，存在于外周血和脾脏中，因含嗜天青颗粒，又称大颗粒淋巴细胞。颗粒内主要含穿孔素和颗粒酶主要通过ADCC作用杀伤靶细胞

*releasekillermediator

perforin(穿孔素)→necrosis

granzyme(颗粒酶)→apoptosis

TNF→necrosis/apoptosis

*mediateADCC•Recognitionandactivation•Killtargetcells(1)non-specific,Abindependent,non-MHCrestriction(2)MechanismofkillingtargetcellTcell分布：粘膜和上皮组织〔外周血含量少〕CD4-CD8-抗原识别谱：－－位于不同组织中的T细胞表达不同特异性的TCR，具有不同的抗原识别特性；－－同一部位组织的T具有相同的抗原识别特性，仅对同一抗原产生应答多聚C9形成的膜攻击复合物MAC的电镜结果补体诱导的细胞膜穿孔损伤

GGGG

ooooMMMM

obobobob

GGGG

oooo

MMMMobobobob

GGGGooooMMMMaaaaccccddddaaaaccccddddxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxN-乙酰葡萄糖胺β-1,4糖苷键N-乙酰胞壁酸四肽侧链

甘氨酸五肽(五肽交联桥)金黄色葡萄球菌细胞壁肽聚糖结构示意图溶菌酶作用点聚糖骨架

PrincipalleukocytesfibroblastslymphocytescellsourceNKcellIFNinducersdsRNAdsRNAmitogensvirusvirusorantigenAntiviralinfection

+++++Anti-tumor++++Immunoregulation++++

PropertyIFN-

IFN-

IFN-

Interferon

(IFN)⑴

definition

干扰素是由病毒或其他干扰素诱生剂刺激机体多种细胞所产生的一种具有抗病毒、抗肿瘤和免疫调节等多种生物学活性的糖蛋白⑵typesandpropertiesbindstosurfacereceptorofneighboringcells⑶

Mechanismofantiviralactivitythesynthesis

ofantiviralprotein(AVP)

induceIFNbyblockingthetranslationofviralproteinsinhibitthereplicationofviruses

AVP:•

2’-5’Asynthetase(2’-5’A合成酶)•proteinkinaseR(蛋白激酶,PKR)•

phosphodiesterase(磷酸二脂酶)(degradeviralmRNA)(inhibittranslationofviralprotein)(inactivateinitiationfactorofprotein-synthesis)

⑷Featureofantiviralactivity

•inhibitreplicationofavarietyofviruses•onlyinhibitreplicationofvirus•species-specific

i.e.broadspectrum(广谱)/non-specific

(notkilldirectlyvirus)thebody’sfirst-linedefenseagainstviralinfection⑸ActionofIFNinantitumorandimmunoregulation

Pathogen-associatedmolecularpatterns,PAMPPatternrecognitionreceptors,PRRToll-likereceptors,TLRPathogen-associatedmolecularpatternsCHALLENGE:Howcanthehostdiscriminatelargenumbersofdiversepathogensfromeachother&/orfromselfusingarestrictednumberofreceptors?SOLUTION:AllmulticellularorganismsareabletorecognizeandeliminatepathogensDespitetheirextremeheterogeneity,pathogenssharehighlyconservedmolecules,called“pathogen-associatedmolecularpatterns〞(PAMPs)2.Mechanismofspecificimmunity(对特异性抗原产生的应答,并获得特异免疫功能)(alsocalledadaptiveimmunity)

Mucosalimmunity

Humoralimmunity(HI)

Cell-mediatedimmunity(CMI)Mucosalimmunity•Unencapsulatedsubepitheliallymphoidfoundinthegastrointestinal,respiratoryandurogenitaltracts•Function*secreteSIgA*takepartinlocalimmuneresponseandsystemicimmuneresponse(i.e.localimmunity)(suchasGALT,BALT,tonsil)

physicalbarrierslikecastlewalls,fencesandpalisades.

Mucosalimmunesystemarenotonlyphysicalbarriersbutalsomightbethehuntinggroundsofprobioticorganisms.Skin,membranesandMISDC’sfunctioninmucosalimmunityImmatureDCdistributewidelyinmucousmembranePlayasabridgeconnectingthenon-specificimmuneresponseandspecificimmuneresponseInteractionbetweenCDandSIgATcelleffectorTcellCD4+Th1CD8+T(CTL)TmBcellplasmacellAb

BmHIAgCMI

Th2(CK)specificimmunity:specificandmemoryHumoralimmunity(HI)•effectormolecule•effectantibodyCell-mediatedimmunity(CMI)

orcellularimmunity•effectorcell

•effect*CD8+

CytotoxicTlymphocyte(CTL)*

CD4+Th1killtargetcelldirectly(feature,mechanism)

*secretecytokine(IL-2,IFN-,TNF-)*inducecellularimmunityandDTH

CTL:CD4+Th1:毒力毒素侵袭力外毒素内毒素入侵门户入侵数量SectionII:Anti-bacteriaimmunity

I.pathogenesisofbacteria黏附与穿入：菌毛繁殖扩散：侵袭性酶抗吞噬与杀伤：荚膜、胞壁等Mechanism1.Immunityofanti-extracellularbacterialinfection2.Immunityofanti-intracellularbacterialinfection

1.Immunityofanti-extracellularbacterialinfectionextracellularbacteria

↓exotoxin/↓endotoxin/↓invasiveenzymelocalpyrogenicinflammation

Barrierstructure

Phagocytosisofphagocyte

Effectofantibodyandcomplement

•preventadhesion

•opsonization•activatecomplement•nutralizeexotoxin

Cellularimmunity

(CD4+Th2→→cytokine)

Others:NKcell,lysozyme,defensin2.Immunityofanti-intracellularbacterialinfection

intracellularbacterial

↓(intracellularparasitism)↓byimmunopathologic↓injury

chronicinfection

Phagocytosisofphagocyte

Cellularimmunity

Mucosalimmunity•CD4+Th1→cytokine→DTH•CTLSIgA:interfereinadhesion

LastedtimeofimmunityNonspecificimmunitySpecificimmunityⅢ.AntiviralimmunityLastedtimeofimmunity

Systemicviralinfectionwithviremia

Viralinfectionwithsingleserotype

Viralinfectionofmuchvariableinantigenicity---transientimmunity---long-lastingimmunity---long-lastingimmunity1.Nonspecificimmunity

Barriers

Effectsofcells

Antiviralsubstancesinnormaltissuesandbodyfluid

(placentabarrier)(M,NK

cell)•virus-neutralizingantibodies

*neutralizeinfectivityofvirus*types(IgG/IgM/sIgA)andmechanism•hemagglutinationinhibitionAb

(inhibithemagglutination;IgG/IgM)•complementfixationAb

(opsonization)2.SpecificimmunityViralprotein

induceB---HIT---CMI(processingandpresenting)

Humo