牙周病與免疫

五、牙周病與免疫(miǎnyì)第一頁，共三十一頁。編輯課件Theoralcavityharborsmorethan700bacterialspecies,coexistingwithprobablymillionsofviralgenomiccopies.口腔定居的細菌有700多種與數(shù)百萬病毒基因組復(fù)制(fùzhì)物共存（ATsuoAmano,2010,Periodontology2000）第二頁，共三十一頁。編輯課件Oralbacteria口腔中的細菌：

--Freetosaliva在唾液(tuòyè)中

--Attachmentinbiofilm附著在生物膜

BetweencloselyrelatedSalivaasacarrier,isconducivetohorizontalandverticaltransmissionofbacteria

第三頁，共三十一頁。編輯課件InUnitedStates,75percentofadultpopulationssufferfromperiodontaldisease.

美國占75%成年人群體不同(bùtónɡ)程度患有牙周病1/3childrenof6~11yearsold,and2/3ofadolescentpopulationhavesomedegreeofperiodontalproblems.1/3的6~11歲兒童，2/3青春期人群也有某種程度的牙周問題第四頁，共三十一頁。編輯課件Over200kindsofbacterialformdentalplaque,adheretothesurfaceoftheteethandgums,andcauseperiodontalinfections.

牙周感染(gǎnrǎn)細菌達200余種PeriodontitisⅠGingivitisbleeding，DeepgingivalPocket<3mm

ⅡPeriodontitisbleeding，swelling，initialboneloss, DeepperiodontalPocket=5mmⅢmajorstagebleeding，swelling，majorboneloss，

DeepperiodontalPocket＞6mm第五頁，共三十一頁。編輯課件

PeriodontalPocket:auniquemicro-environment

牙周袋是獨特的微環(huán)境escapethephysicalseparationforce逃逸物理分離力hardtissuesurface不剝脫更新的硬組織表面junctionalepithelialization,basicallynotdifferentiation有結(jié)合上皮，基本上不分化(fēnhuà)non-keratinizingepithelium無角化facultativeanaerobic→anaerobic兼性厭氧→厭氧nutrition,humidity,pH,Eh營養(yǎng)、濕度、pH、Eh第六頁，共三十一頁。編輯課件第七頁，共三十一頁。編輯課件齦下細菌(xìjūn)附著和聚集模式圖RootsurfacePellicleP.gP.gP.gP.gP.g第八頁，共三十一頁。編輯課件Subgingivalbiofilmformation

齦下生物膜形成

Initialcolonization早期(zǎoqī)定居者：

actinomyces,

streptococci

succeededcolonization微生物交替后：

periodontalpathogens致病微生物定植

Pg，AA,forsythia,T.denticole Fusobacteriumnucleatum

第九頁，共三十一頁。編輯課件第十頁，共三十一頁。編輯課件1996confirmedthreebacteriaforperiodontalpathogens:

Actinobacillusactinomycetemcomitans(AA)Tannerellaforsythia(TF)Porphyromonasgingivalis(Pg)1996,牙周致病菌

AA，TF，PgRecentviewschange,pathogeniccapacityofAAandotherculturableornon-culturablebacteriashouldbeconfirmed.

近期(jìnqī)：AA待證實第十一頁，共三十一頁。編輯課件50%oralmicrobialcannotbecultivatedandcanbeidentifiedthroughextramethods:口腔中有50%微生物不能培養(yǎng)，可通過下述方法(fāngfǎ)鑒定：quantitativeRT-PCR定量PCRphylogenetic16s-rRNAgeneclonelibraryanalysis

用基因組或16srRNA探針checkerboardhybridization棋盤雜交high-throughputfingerprinttechnology高通量指紋技術(shù)pyrophosphatesequencing454技術(shù)（焦磷酸鹽測序）metagenometechnology宏基因組技術(shù)第十二頁，共三十一頁。編輯課件Generalview:PeriodontitisiscausedbyendogenousG-periodontalbacteria.

目前普遍認為：牙周炎是由內(nèi)源性G-牙周細菌所致(suǒzhì)

Redcomplex:Porphyromonasgingivalis牙齦卟啉菌Tannerellaforsythia弗賽菌Treponemadenticola齒密螺旋體Potentialvirulencefactors潛在毒力因子Neutralizationforlocalhostdefensemechanisms中和局部宿主防御機制Destructionofperiodontaltissue破壞牙周組織第十三頁，共三十一頁。編輯課件P.Gingivalis牙齦卟啉菌G-厭氧、桿狀、繖附著、與紅色菌群共同構(gòu)成生物膜adheretohostcells（integrins）通過整合素附著Secretoryproteinase分泌蛋白溶解酶、破壞牙齦附著Afterinvasion,associationwiththechangeofintracellularsignalingpathways入侵后改變信號通路分泌脂多糖，是細菌(xìjūn)內(nèi)毒素的主要成分畸形血管生成第十四頁，共三十一頁。編輯課件Tannerellaforsythia弗賽菌厭氧G-菌，cytophaga-BacteroidetesfamilyNewpathogensthrough16srRNAdetection16srRNA檢測分泌富含亮氨酸的重復(fù)蛋白（leucine-rich-repeatprotein,BSPA）,使細菌容易(róngyì)附著，是重要的毒力因子啟動單核細胞釋放炎癥細胞因子，成骨細胞釋放趨化因子，導(dǎo)致炎癥和骨吸收第十五頁，共三十一頁。編輯課件G-口腔螺旋體家族，絕對厭氧，纖細(xiānxì)、螺旋、能動、可彎曲Virulencefactors毒力因子——內(nèi)毒素Accumulationingingivalpocket,usingavarietyofnutritioningredients聚集于牙周袋Degradationofcytokines，inhibitionoffibroblastmigration,andpreventionofhealing降解細胞因子Treponemadenticola齒密螺旋體第十六頁，共三十一頁。編輯課件Becausesubgingivalmicrobialbetweenperiodontalhealthanddiseaseindividualsaresignificantdifferences,simplepathogensmodecannotexplaintheetiologyofperiodontitis.Currenttheoriestendtoapplymicroorganismsuccessiontoexplaintheetiologyofperiodontitis,i.e.benignbacteriareducingresultsintheincreaseofpathogenbacteria.Insomedegree,thewholemicrobialcommunityisitspathogen.單一致病源不能解釋牙周病模式微生物交替(jiāotì)可解釋牙周病病因第十七頁，共三十一頁。編輯課件Host-microorganismsinteractionshasestablishedthebasicframework,whichcanformaperiodontalinflammation,butalsooffersthepossibilityoftreatment.

宿主—寄生物相互作用已建立一種(yīzhǒnɡ)基本性框架，可形成牙周炎癥，也提供了治療的可能性第十八頁，共三十一頁。編輯課件Subgingivalinfection

齦下感染

Bacteriaadhesion-growth-biofilmformation-intrusionofhosttissues-invasionofhostimmunesysteminterface

細菌附著—粘附—細胞生長—生物膜形成—致病源入侵(rùqīn)宿主細胞/組織—侵犯宿主免疫系統(tǒng)界面第十九頁，共三十一頁。編輯課件Periodontaldisease&hostimmunity

牙周病與宿主(sùzhǔ)免疫第二十頁，共三十一頁。編輯課件46%peoplecanbedetectedperiodontalpathogens.However,manyindividualsmaylimittheoccurrenceofperiodontaldisease.Manyscholarshaveproposedthemultipleetiologyofperiodontaldisease:

microbes,hostimmuneresponse,environmentalfactors…

46%檢測到牙周致病菌，但許多人不發(fā)病牙周病病因涉及(shèjí)微生物、宿主、環(huán)境第二十一頁，共三十一頁。編輯課件Althoughperiodontaldiseaseiscausealbybacterialinfection,theresultingtissuedamageisduetotheimmuneresponse.牙周病損傷來自免疫(miǎnyì)反應(yīng)第二十二頁，共三十一頁。編輯課件Individualimmuneresponsestoalargeextentdeterminetheseverityofperiodontaldisease.個體反應(yīng)決定牙周損害程度Twinstudyconfirmsgenetichereditaryeffectsonperiodontaldiseaseclinicalsensitivityupto50%.遺傳(yíchuán)因素占50%第二十三頁，共三十一頁。編輯課件

Firstistheinnateimmuneresponse

Bacterialuptakebymacrophages→cytokenreleasebymacrophages

巨噬細胞釋放細胞因子→causingperiodontaldiseasesrelatedtoinflammation

炎癥(yánzhèng)→causingbloodvesselstodilate,permeabilityincreases

血管滲透性增加→localbloodflowincreases,creatinginflammation

血流量增加

Innateimmuneresponse

固有(gùyǒu)免疫反應(yīng)第二十四頁，共三十一頁。編輯課件Acquiredimmuneresponses獲得性免疫反應(yīng)Pgisthemostofbacteriarelatedtoperiodontalinflammation,cansensitizedandactivateDCPg致敏并激活(jīhuó)

DCDendriticcells(DC)playaroleinantigenpresentation→NaiveTcellsstimulated

DC→刺激幼稚T細胞→reachesthenearestlymphnode→activateTcells

到達附近淋巴結(jié)，激活T細胞第二十五頁，共三十一頁。編輯課件Immuneescape免疫逃逸Pathogenicbacteriaofperiodontitismayentercells,escapeimmunesurveillance,andformecologicalbalancewithhost.Oncebalancedamage,periodontaldiseasecanhappen.

牙周致病菌進入細胞逃逸免疫監(jiān)視；病毒(bìngdú)的作用Synergism協(xié)同作用:Oralherpesvirus,EBvirusandbacterial第二十六頁，共三十一頁。編輯課件第二十七頁，共三十一頁。編輯課件CD4+Tcellsappearanceisthemaincauseofperiodontalboneloss.CD4+T細胞(xìbāo)Th2cellsactivateBcellstoproduceantibodies.Th2激活B細胞Epithelialcellsinpe