1、五、牙周病与免疫五、牙周病与免疫 The oral cavity harbors more than 700 bacterial species,coexisting with probably millions of viral genomic copies.口腔定居的细菌有口腔定居的细菌有700多种多种 与数百万病毒基因组复制物共存与数百万病毒基因组复制物共存 （A Tsuo Amano,2010,Periodontology 2000）Oral bacteria 口腔中的细菌口腔中的细菌：-Free to saliva 在唾液中在唾液中 -Attachment in biofilm 附着
2、在生物膜附着在生物膜 Between closely related Saliva as a carrier,is conducive to horizontal and vertical transmission of bacteria In United States,75 per cent of adult populations suffer from periodontal disease.美国占美国占75%成年人群体不同程度患有牙周病成年人群体不同程度患有牙周病 1/3 children of 611years old,and 2/3 of adolescent populatio
3、n have some degree of periodontal problems.1/3的的611岁儿童，岁儿童，2/3青春期人群也有某种程度的青春期人群也有某种程度的牙周问题牙周问题 Over 200 kinds of bacterial form dental plaque,adhere to the surface of the teeth and gums,and cause periodontal infections.牙周感染细菌达牙周感染细菌达200余种余种 Periodontitis Gingivitis bleeding，Deep gingival Pocket 3mm
4、Periodontitis bleeding，swelling，initial bone loss,Deep periodontal Pocket=5mm major stage bleeding，swelling，major bone loss，Deep periodontal Pocket 6mm Periodontal Pocket:a unique micro-environment 牙周袋是独特的微环境牙周袋是独特的微环境 escape the physical separation force 逃逸物理分离力逃逸物理分离力 hard tissue surface 不剥脱更新的硬组织
5、表面不剥脱更新的硬组织表面 junctional epithelialization,basically not differentiation有结合上皮，基本上不分化有结合上皮，基本上不分化 non-keratinizing epithelium 无角化无角化 facultative anaerobic anaerobic 兼性厌氧兼性厌氧厌氧厌氧 nutrition,humidity,pH,Eh 营养、湿度、营养、湿度、pH、Eh 龈下细菌附着和聚集模式图龈下细菌附着和聚集模式图 Root surface Pellicle P.g P.g P.g P.g Subgingival biofi
6、lm formation 龈下生物膜形成龈下生物膜形成 Initial colonization早期定居者早期定居者：actinomyces,streptococci succeeded colonization 微生物交替后：微生物交替后：periodontal pathogens 致病微生物定植致病微生物定植 Pg，AA,forsythia,T.denticole Fusobacterium nucleatum 1996 confirmed three bacteria for periodontal pathogens:Actinobacillus actinomycetemcomita
7、ns(AA)Tannerella forsythia(TF)Porphyromonas gingivalis(Pg)1996,牙周致病菌牙周致病菌 AA，TF，Pg Recent views change,pathogenic capacity of AA and other culturable or non-culturable bacteria should be confirmed.近期：近期：AA待证实待证实 50%oral microbial cannot be cultivated and can be identified through extra methods:口腔中有口
8、腔中有50%微生物不能培养，可通过下述方法鉴定：微生物不能培养，可通过下述方法鉴定：quantitative RT-PCR 定量定量PCR phylogenetic 16s-rRNA gene clone library analysis 用基因组或用基因组或16s rRNA探针探针 checkerboard hybridization 棋盘杂交棋盘杂交 high-throughput fingerprint technology 高通量指纹技术高通量指纹技术 pyrophosphate sequencing 454技术（焦磷酸盐测序）技术（焦磷酸盐测序）metagenome technolo
9、gy 宏基因组技术宏基因组技术 General view:Periodontitis is caused by endogenous G-periodontal bacteria.目前普遍认为：牙周炎是由内源性目前普遍认为：牙周炎是由内源性G-牙周细菌所致牙周细菌所致 Red complex:Porphyromonas gingivalis 牙龈卟啉菌牙龈卟啉菌 Tannerella forsythia 弗赛菌弗赛菌 Treponema denticola 齿密螺旋体齿密螺旋体 Potential virulence factors 潜在毒力因子潜在毒力因子 Neutralization fo
10、r local host defense mechanisms 中和局部宿主防御机制中和局部宿主防御机制 Destruction of periodontal tissue 破坏牙周组织破坏牙周组织 P.Gingivalis 牙龈卟啉菌牙龈卟啉菌 G-厌氧、杆状、繖附着、与红色菌群共同构成生物膜厌氧、杆状、繖附着、与红色菌群共同构成生物膜 adhere to host cells（integrins）通过整合素附着）通过整合素附着 Secretory proteinase 分泌蛋白溶解酶、破坏牙龈附着分泌蛋白溶解酶、破坏牙龈附着 After invasion,association with
11、the change of intracellular signaling pathways 入侵后改变信号通路入侵后改变信号通路 分泌脂多糖，是细菌内毒素的主要成分分泌脂多糖，是细菌内毒素的主要成分 畸形血管生成畸形血管生成 Tannerella forsythia 弗赛菌弗赛菌 厌氧厌氧G-菌，菌，cytophaga-Bacteroidetes family New pathogens through 16s rRNA detection 16s rRNA检测检测 分泌富含亮氨酸的重复蛋白（分泌富含亮氨酸的重复蛋白（leucine-rich-repeat protein,BSPA）,使细菌
12、容易附着，是使细菌容易附着，是重要的毒力因子重要的毒力因子 启动单核细胞释放炎症细胞因子，成骨细胞释放启动单核细胞释放炎症细胞因子，成骨细胞释放趋化因子，导致炎症和骨吸收趋化因子，导致炎症和骨吸收 G-口腔螺旋体家族，绝对厌氧，纤细、螺旋、能动、口腔螺旋体家族，绝对厌氧，纤细、螺旋、能动、可弯曲可弯曲 Virulence factors 毒力因子毒力因子内毒素内毒素 Accumulation in gingival pocket,using a variety of nutrition ingredients 聚集于牙周袋聚集于牙周袋 Degradation of cytokines，inhi
13、bition of fibroblast migration,and prevention of healing 降解细胞因子降解细胞因子 Treponema denticola 齿密螺旋体齿密螺旋体 Because subgingival microbial between periodontal health and disease individuals are significant differences,simple pathogens mode can not explain the etiology of periodontitis.Current theories tend
14、to apply microorganism succession to explain the etiology of periodontitis,i.e.benign bacteria reducing results in the increase of pathogen bacteria.In some degree,the whole microbial community is its pathogen.单一致病源不能解释牙周病模式单一致病源不能解释牙周病模式 微生物交替可解释牙周病病因微生物交替可解释牙周病病因 Host-microorganisms interactions h
15、as established the basic framework,which can form a periodontal inflammation,but also offers the possibility of treatment.宿主宿主寄生物相互作用已建立一种基本性框架，寄生物相互作用已建立一种基本性框架，可形成牙周炎症，也提供了治疗的可能性可形成牙周炎症，也提供了治疗的可能性 Subgingival infection 龈下感染龈下感染 Bacteria adhesion-growth-biofilm formation-intrusion of host tissues-i
16、nvasion of host immune system interface 细菌附着细菌附着粘附粘附细胞生长细胞生长生物膜形成生物膜形成致病源入侵宿主细胞致病源入侵宿主细胞/组织组织侵犯宿主免疫系侵犯宿主免疫系统界面统界面 Periodontal disease&host immunity 牙周病与宿主免疫牙周病与宿主免疫 46%people can be detected periodontal pathogens.However,many individuals may limit the occurrence of periodontal disease.Many scholars have proposed the multiple etiology of periodontal disease:microbes,host immune response,environmental factors 46%检测到牙周致病菌，但许多人不发病检测到牙周致病菌，但许多人不发病 牙周病病因涉及牙周病病因涉及 微生物、宿主、环境微生物、宿主、环境 Although periodonta
