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1、老年免疫学 Background thepopulationoftheworldage60orolderwillbe2billion 20亿 by2050 wheremorethan30 ofthepopulationisexpectedtobeage60orolderin2050inchinaitwillofcoursebenecessarytodevotemoreresourcestothecareandhealthoftheelderly itwillbenefitbyadoptingprogramsthataimtodiminishbehaviorsthatleadtochronicc
2、onditions SourceData UnitedNations 2009 PopulationandFertilityRate China stotalfertilityratefellfromaround6in1950 1970to2in1990 1995 Thefertilityratewasbelow2by1995 Thedecline whichwasespeciallyrapidbetween1970and1980 深入研究老年免疫的特征 与疾病的相关性 对老年性疾病的诊断 预防和治疗具有重要意义 老年免疫的特征典型老年疾病的预防和治疗 Immunesystem Immuneo
3、rgansandtissuescentral bonemarrow thymusperipheral lymphnode spleen mucosal associatedlymphoidtissueImmunocytesinnateimmunity M NK DC granulocyte etcadaptedimmunity lymphocyteImmunologicalmoleculesClassifiedbasedonstructurecytokines chemokinesandtheirreceptorscomplementsandtheirregulatorymoleculesdi
4、fferentiationantigens CDantigen adhesionmoleculesproductsofTCR BCR MHCgenesClassifiedbasedonfunctionmoleculesinimmunocytedifferentiationmoleculesininflammation moleculesinantigen recognitionandcostimulationmoleculesinsignaltransductionforimmunocyteactivationmoleculesinapoptosisandcelldeath 免疫学基础 识别
5、活化 效应 抗原 Ag 双识别体液免疫抗原提呈细胞 APC 双信号细胞免疫 Immunity2006 24 677 688 1 免疫调节功能 Th1 Th2 Tr 2 特异性杀伤功能 CTL Th1 gdT T细胞的功能 CTL对靶细胞的特异性杀伤 效靶细胞的结合CTL的极化杀伤靶细胞 CTL直接杀伤靶细胞 穿孔素 颗粒酶Fas FasL TNFR TNF 三大功能 产生抗体 中和作用 调理作用提呈抗原 专职APC 籍BCR结合可溶性抗原分泌细胞因子 参与免疫调节 炎症反应 造血过程 B细胞功能 免疫器官和细胞的发育分化有其鲜明特征 胸腺是T细胞发育的重要器官 胸腺对衰老敏感 胸腺对衰老很敏感
6、 免疫器官和细胞的发育分化有其鲜明特征 CLP DN Pre TCR DP TCR CD4 CD8 CD4SP TCR CD4 阳性选择 阴性选择 TCR brearrangement TCR arearrangement TCR CD8 CD8SP 双阴性 双阳性 单阳性 基因重排 阳性 阴性选择 免疫器官和细胞的发育分化有其鲜明特征 成熟T细胞在外周进行进一步分化 InnateimmunityAdaptiveimmunity MemoryTcellfrequency pathogensusceptibilityandmortalitythroughouthumanlife Thereisa
7、nincreaseinthefrequencyofmemoryTcellsintheblood redline overtime Inthewholebody whichincludestheblood intestines lungs skin liver brainandlymphoidtissues theoverallfrequencyofmemoryTcells blackline alsoincreaseswithage TheincreaseinmemoryTcellfrequencythroughoutthebodyinverselycorrelateswithadecreas
8、edsusceptibilitytopathogeninfection dashedline Atbirth allTcellsintheperipheralbloodarenaive andmemoryTcellsdevelopovertimeinresponsetoexposuretodiverseantigens AmarkedincreaseintheproportionofcirculatingmemoryTcellsoccursinthefirstdecadeoflifememoryTcellsconstituteupto35 ofcirculatingTcellsbytheend
9、oftheseconddecadeoflifeDuringthisinitialmemorygenerationphase particularlyduringinfancyandearlychildhood individualshavethehighestsusceptibilitytopathogens asmeasuredbyinfectiousdiseasehospitalizationrates memoryhomeostasis beginsinthethirddecadeoflife whencirculatingmemoryTcellfrequenciesreachaplat
10、eauandremainstablethroughoutadulthoodThymicoutputgraduallydecreasesduringthisphaseandTcellnumbersaremostlymaintainedthroughhomeostaticcellturnoverIndividualsinthesemiddleyearsoflifearelesssusceptibletopathogens asshownbythelowhospitalizationrateofinfectiousdiseases AfterdecadesofstablememoryTcellfre
11、quencies theproportionandthefunctionalityofmemoryTcellsbecomesalteredduringimmunosenescence startingat65 70yearsofageImmunosenescence 免疫衰老 alsomarksanincreasedsusceptibilitytopathogensthatispartlycausedbyage associatedimmunedysregulationandnon immune relatedphysiologicaldecline 老年免疫的特征典型老年疾病的预防和治疗老年
12、带状疱疹的预防性疫苗与免疫治疗老年痴呆症的免疫学治疗老年心血管疾病的治疗 Immunetherapyforage relateddiseases threeofthemostimportantdiseasesofaging shingles Alzheimer sdiseaseandatheroscleroticcardiovasculardisease allofthesediseaseshavesignificantimmunologicalcomponentsineithertheiretiology 病因学 and orprogression suggestingthatappropr
13、iateimmuneinterventioncouldbeusedintheirpreventionortreatment 带状疱疹的预防 针对老年三大疾病之一的带状疱疹疾病的预防性疫苗 带状疱疹疫苗于2006年在美国上市 并被推荐用于大于60岁免疫力健全的老年人 通过随机对照及长期随访 证实了该带状疱疹疫苗的短期和长期安全性 DevelopmentofaVZVvaccineforshingles Shinglesismanifestedbyapainful vesicularskineruptionusuallylimitedtothedistributionofasinglesensory
14、nervearisingfromitsdorsalganglion 背侧神经节 Thelifetimeriskofshinglesis33 withthediseasemostoftenaffectingpersonsover60yearsofage Upto20 ofpatientswithshinglesdevelopdebilitating 衰弱 postherpeticneuralgia 带状疱疹后神经痛 PHN andtheriskofthiscomplicationincreaseswithageover60 ThepainofPHNoccursinthesamedistribut
15、ionastherashofshinglesbutcanpersistformonthsorevenyearsaftertherashofshingleshasdisappeared bothlaboratoryandclinicalobservationshaveproventhatshingles 带状疱疹 andchickenpox 水痘 arecausedbythesamevirus nowtermedtheVZV 水痘带状疱疹病毒 therelationshipbetweenincreasingageandtheincreasingincidenceofshingleswith 1c
16、hildin1000under5yearsolddevelopingshingles Between5and20yearsofage theincidenceofshinglesdoublesandremainsatthisleveluntil50yearsofage thereisalinearincreaseintheincidenceofzosterfrom2per1000at50yearsofageto10per1000at90yearsofage ThefrequencyofVZV respondingTcellswithintheperipheralbloodmononuclearcells PBMCs in60 to87 yearoldindividualsislowerthaninyoungerindividuals itwassubsequentlyshownthatanageassociateddeclineinVZV specificTcells Figure1a andnotthelevelofVZV specificantibodiescorrelatedwi
