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1、Immuno-Seq:exploringthediversityofimmunesystemJiankuiHeSouthUniversityofScienceandTechnologyofChina(SUSTC),Shenzhen,ChinaThediversityofInvaders...BacteriaVirusesparasitessuchasfungi,protista,&wormsPhysicalinjuryTheImmuneSystemInnateimmunesystemageneralresponsetoanythingothert
2、hanrecognized“selfcells”macrophages-abletoingestsmallforeigninvadersMastcells/basophilsreleasehistaminethatdilatesbloodvesselscausesrednessAdaptiveimmunesystemaspecificcounter-assaultagainsta“knownforeign”invader[previouslyrecognized]Key-lockEverymatureTcell(Bcell)expressesas
3、ingleTCR(BCR)withspecificityforalimitednumberofantigens.TcellreceptorHowmanyTcellsinyourbody?1.HumanbloodhasaboutonemillionTcellsineverymilliliter(ml).2.Theaverageadulthumanhasabout10litersofblood.3.Thereare10,000mlin10L.4,So,thereareaboutonemillionx10,000Tcellsinthebloodstre
4、am.Thiscomesto1010.About1/50ofallTcellsarefoundintheblood.Mostoftherestareinthespleenandlymphnodes.Somearealsofoundinthebonemarrow,liver,andothertissues.5.So,IwouldestimatethenumberofTcellsinthehumanbodytobeabout5x1011.BlymphocytedevelopmentHowantibodydiversityisgeneratedJane
5、wayC.,Immunobiology,2004StemcellChromosome14,heavychainBlymphocytedevelopmentHowantibodydiversityisgeneratedJanewayC.,Immunobiology,2004StemcellChromosome14,heavychainPro-BcellBlymphocytedevelopmentHowantibodydiversityisgeneratedJanewayC.,Immunobiology,2004StemcellBcellChromo
6、some14,heavychainPro-BcellHumanHeavychainVgenesegments~50HeavychainDgenesegments27HeavychainJgenesegments6AntibodyrepertoireestimatesVDJcombination50*27*6=8,000Potentialantibodydiversity~1014Jointdiversity3-5bprandominsertion/deletionTheoreticalcalculation:Immunesystemonlyuse
7、s83geneSegmenttocode1014BCRsequencesDiversityandhealthyIntrinsicfactorsthatinfluencetheexpressionoftheTCRrepertoireinhumans:humanMHC(HLA)systemandTCRgenepolymorphisms,Extrinsicfactors:environmentalfactors,suchasinfectionandsuperantigens.InnormalindividualstheTCRrepertoireisst
8、ableandpolyclonal.clonalpopulationsarethehallmarkofmalignancy,clonal
