医学免疫学教学课件：MHC complement

TheMHCComplementMHC

MajorHistocompatibility

ComplexHuman:HLAMouse:H-2T-cellsrecogniseantigenthatis:a)Processedintopeptides

then:b)PresentedbyMHC MHC

2mainversions:

MHCclassIfoundonallnucleatedcellsinthebody

MHCclassIIfoundon‘professionalantigen-presentingcells’(APC):Dendriticcells,macrophages,B-cells

(alsoonthymicepitheliumandactivatedhumanT-cells)

MHCclassIspecializedforalertingcytotoxicT-cellstointracellularinfection

MHCclassIIspecializedforactivatinghelperT-cellsHumanMHCClassI:HLA-A,-B,-CHumanMHCClassII:HLA-DP,-DQ,-DRMouseMHCClassI:H-2K,H-2D,H-2LMouseMHCClassII:I-A,I-EMHCClassIIIdoesnotencodeantigen-presentingmolecules,butdoesencodethecomplementcomponentsC2,C4&FactorB,thecytokinesTNFandlymphotoxin,etcThehumanandmouseMHCgenelociPolymorphicHLAspecificitiesandtheirinheritanceStructureofMHCmoleculesStructureofMHCmoleculesPeptidebindsintoMHCpeptide-bindinggroovePeptidebindsintoMHCpeptide-bindinggrooveMHCH-2KbSecondaryanchorMainanchorMainanchorKochC.P.etal.(2013)ScrutinizingMHC-IBindingPeptidesandTheirLimitsofVariation.PLoSComputBiol9(6):e1003088.Y=TyrosineF=PhenylalanineL=LeucineM=MethionineI=IsoleucineV=ValineMajoranchorresiduesdeterminepeptidebindingtoMHCClassIpresentspeptidestoCD8+

cytotoxicTcellsClassIIpresentspeptidestoCD4+helperTcellsAntigenpresentationbyMHCTheimportanceofMHCintransplantationHost-versus-graftreactionsFirstcadaverickidneygraftsurvivalRecognitionofgraftantigensbyalloreactiveT-cellsMHCisageneticfactorinautoimmunediseaseMHCisageneticfactorinautoimmunediseaseSummaryMHCpresentsprocessedantigentotheTCRonT-cellsMHCgenesarethemostpolymorphicgenesinthehumangenomeInhumanMHCclassIisHLA-A,-B,-CandMHCclassIIisHLA-DP,-DQ,-DRMHCisthestrongestgeneticdeterminantoftransplant rejection(particularlyHLA-A,-Band-DR)ParticularMHCvariantsareassociatedwithautoimmunediseasesTheMHCComplementPeterJDelvesp.delves@ucl.ac.ukComplementAsetof~20ormoredifferentproteinsActinanenzymicamplificationcascadeUponactivationthecomplementsystemgeneratesanumberofactivecomponentsinvolvedinseveralaspectsoftheimmuneresponseincludingacuteinflammationAcuteinflammationThetissueresponsetoinjuryorinfectionCharacterisedbyincreasedbloodflowandentryofleukocytesintothetissuesResultsin:swellingrednesselevatedtemperaturepainThreewaystoactivatecomplement:ClassicalpathwayLectinpathwayAlternativepathwayComplementactivationpathwaysComplementactivationpathwaysComplementactivationpathwaysComplementactivationpathwaysComplementactivationpathwaysComplementactivationpathwaysComplementactivationpathwaysComplementactivationpathwaysComplementactivationpathwaysC3convertasecleavesC3intoC3a+C3bSplittingofC3isakeyeventincomplementactivationO.K.,butwhatdoescomplementactuallydo?ComplementcomponentsinvolvedinimmuneresponsesComplementcomponentsinvolvedinimmuneresponsesComplementcomponentsinvolvedinimmuneresponsesComplementcomponentsinvolvedinimmuneresponsesComplementcomponentsinvolvedinimmuneresponsesActivitiesgeneratedbythetriggeringofthecomplementcascadeComplementregulatoryproteinsOpsonisationLysis-themembraneattackcomplexFormationofthemembraneattackcomplex(C5b-9)C3a,C4aandC5aactivatemastcellsE-selectinCD15

SummaryInflammationrapidlyrecruitsneutrophilstothesiteoftheinfectionComplementplaysakeyroleinthisprocessbycausingmastcelldegranulat