麻风与固有免疫双语课件

Leprosyandinnateimmunity

麻风与固有免疫YuangangYouBeijingTropicalMedicineResearchInstituteLeprosyCausedby

Mycobacteriumleprae

Rod-shapedbacteria

GerhardH.ArmauerHansen

Prevalence

Inthesecountriesthereis1caseper10,000population

IncubationPeriodTheincubationperiodforleprosyisabout5years.

Itcouldtake20yearsforsymptomstoappear.TherouteoftransmissionNotbeendefinitivelyestablished.Althoughhuman-to-humanaerosolspreadofnasalsecretionsisthemostlikelymodeoftransmissioninmostcases.Thediseaseisnotspreadbytouch,sincethemycobacteriaareincapableofcrossingintactskin.Livingnearpeoplewithleprosyisassociatedwithincreasedtransmission.Amonghouseholdcontacts,therelativeriskforleprosyisincreased8-to10-foldinmultibacillaryand2-to4-foldinpaucibacillaryforms.Animalreservoirsdoexist(armadillos,redsquirrel，certainnonhumanprimates),andcasesofsuspectedzoonotictransmissionhavebeenreported.TherouteoftransmissionSymptomsTuberculoidLeprosySymptoms

SeverepainMuscleweaknessSkinstiffnessanddrynessLossoffingersandtoesEyeproblemsBlindenessEnlargednervesLepromatousLeprosySymptomThickenedskinonfaceNasalstuffinessBloodynoseLaryngitisCollapsingofthenoseSwellingofthelymphnodesinthegroinandarmpitsScarringofthetestesthatleadstoinfertilityEnlargementofmalebreastsThereistwowaysleprosyispresented:.SubsequenttoM.lepraeexposure,group1genesconfersusceptibility(orresistance)totheestablishmentofinfectionanddevelopmentofclinicaldisease(i.e.,leprosyperse).Amongtheapproximately5–10%ofindividualswhodevelopleprosy,group2genesdeterminethetypeofhostimmuneresponseelicitedandsubsequentclinicalsubtypemanifested(single-lesionPB,PB,MB)Two-stagemodelofgeneticsusceptibilitytoleprosyLeprosyasageneticdisease,MammGenome,DOI10.1007/s00335-010-9287-1Two-stagemodelofgeneticsusceptibilitytoleprosyGeneAssociationwithLeprosy:AReviewofPublishedData

FrontiersinImmunology,2016Jan12(ISSN:1664-3224)InfectiousdiseaseandimmunologyInthemajorityofinfectiousdiseasesonlyaproportionofindividualsexposedtoapathogenbecomeinfectedanddevelopclinicallyevidentdisease.thisinterindividualvariabilityisdeterminedbythecombinedeffectofhostproteinsencodedbyaseriesofgenesthatcontrolthequantityandqualityofhost-pathogeninteractionandhostimmuneresponses.Thereisconsiderablecurrentinterestinanalysisofinitialrecognitionofpathogensbyinnateimmunemechanisms,andtranslationintosignalsthatalertanddirecttheadaptiveresponse.Thisismediatedinpartbythefamilyoftoll-likereceptorsonmacrophagesanddendriticcells,andincludesreleaseofaseriesofproinflammatorycytokines.M.lepraecanaccumulateintissuestomuchhigherlevelsthanM.tuberculosis,andappearstopresentalesspotentproinflammatorystimulus.Comparisonofresponsestothetwopathogens,togetherwithknowledgeofsurfacecomponents,maybeusefulinidentifyingmoleculardeterminantsregulatinginnateimmunerecognition.UnderstandingofinflammatoryresponsestoM.lepraeisofparticularimportanceinthecontextofleprosyreactions.Leprosyprovidesamodeltoinvestigatemechanismsofimmuneregulationinhumans,giventhatthediseaseformsaspectrumofclinicalpresentationsthatcorrelatewithhostimmuneresponses.InnateimmunityandleprosyphenotypicspectrumofleprosyHostgeneticdiversityandimmunesystem麻风的免疫光谱现象和个体的免疫状态相关

Atoneendofthespectrum,inT-lep,theinfectionisself-limited,andskinlesionsaretypifiedbyanadaptiveimmuneresponsecharacterizedbyThelpertype1(TH1)cytokinesandaninnateimmuneresponsecharacterizedbymacrophagesprogrammedtoexpressthevitaminD–mediatedantimicrobialpathway.Attheotherendofthespectrum,inL-lep,theinfectionisdisseminatedwithlesionstypifiedbyanadaptiveimmuneresponsecharacterizedbyTH2cytokinesandaninnateimmuneresponsecharacterizedbymacrophagesprogrammedtoexpressaphagocyticactivity.

ImmunespectrumofleprosyClinicalmanifestationsofleprosyareclassifiedaccordingtotheRidley-Jopling(TT,BT,BB,BL,LL)andWorldHealthOrganization(PBandMB)schemes.Thehostimmuneresponse(Th1versusTh2)andbacillaryloadcorrelatedwitheachleprosysubtypeisindicatedbelowClinicalandimmunologicalclassificationoftheleprosydiseasespectrumLeprosyasageneticdisease,MammGenome,DOI10.1007/s00335-010-9287-1固有免疫细胞回和固有免疫细胞：巨噬细胞（Macrophage）巨噬细胞吞噬细菌模式识别Macrophageshelpdestroybacteria,protozoa,andtumorcells.Toll-likereceptorsmediatespathogenpatternrecognition.PRRandleprosyTLR,NOD2,MDP,etc.ThesePRRhasbeenpriovedtoassoiatedwithleprosySignalingtoll-likereceptorsandinteraction

withcellsoftheimmunesystem

Macrophagesareoneofthemostabundanthostcellstocomeincontactwithmycobacteria.Pathogenicmycobacteriahaveadoptedvariousstrategiestoinvadetheirhosts,buttheexactmechanismofinternalizationofthebacteriabyphago-cyticcellsisunknown.1)DC-SIGNcanactasanentryreceptorforM.Leprae;2)TLR2–TLR1heterodimersseemtomediatecellactivationbykillingM.Leprae.MechanismsofM.lepraeuptake&nonresponsivenessinleprosyLeprosyasamodelforhostdefenseversuspathogenesisfortheinnateimmuneresponsetomycobacterialinfectionVitaminDandinnateimmunityNatMed.