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1、Chapter 7 抗原呈递细胞 Still waters run deep.流静水深流静水深,人静心深人静心深 Where there is life,there is hope。有生命必有希望。有生命必有希望 Antigen presenting cell(APC)Definition Definition n nAPC is a cell that displays peptide APC is a cell that displays peptide fragment of protein antigens,in fragment of protein antigens,in asso
2、ciation with MHC molecules,on its association with MHC molecules,on its surface and activates antigen-specific T surface and activates antigen-specific T cells.In addition to displaying peptide-cells.In addition to displaying peptide-MHC complexes,APCs must also express MHC complexes,APCs must also
3、express costimulatory molecules to activate T costimulatory molecules to activate T lymphocytes optimallylymphocytes optimally.T cells do not recognise native antigensYYBYYYYYYYBYTYT活化增殖、产生抗体无增殖无CK产生BCR交联YBYBYBYBYBYBYBCell surfacepeptidesof AgAntigens must be processed in orderto be recognised by T
4、cellsYT T cellresponse无应答无应答无应答无应答Solublenative AgCell surfacenative AgSoluble peptidesof Ag抗原肽抗原肽-MHC复合物复合物抗原加工、递呈 第一节第一节 抗原提呈细胞的种类抗原提呈细胞的种类 Professionals APC:l lDendritic cellsDendritic cellsl lMacrophagesMacrophagesl lB cellsB cellsn nNon-professional APC：在某些活性分子刺激下能被诱导表达在某些活性分子刺激下能被诱导表达MHC-II类分子
5、并能处理和提呈抗原的细胞类分子并能处理和提呈抗原的细胞。包括：。包括：内皮细胞；纤维母细胞；上皮及间皮细胞；嗜酸内皮细胞；纤维母细胞；上皮及间皮细胞；嗜酸性粒细胞等。抗原提呈能力弱。性粒细胞等。抗原提呈能力弱。n n广义广义APC：指能加工处理抗原并以抗原肽：指能加工处理抗原并以抗原肽-MHC分子复合物的形式提呈抗原信息的所有细胞。分子复合物的形式提呈抗原信息的所有细胞。n nClassification and distributionClassification and distributionClassification and distributionClassification an
6、d distribution DC in DC in lymphoid tissue:Interdugutating DC:Interdugutating DC:分布于淋巴组织胸腺依赖区和次分布于淋巴组织胸腺依赖区和次分布于淋巴组织胸腺依赖区和次分布于淋巴组织胸腺依赖区和次级淋巴组织级淋巴组织级淋巴组织级淋巴组织 F Folliculus DC:DC:分布于外周淋巴器官淋巴滤泡生分布于外周淋巴器官淋巴滤泡生分布于外周淋巴器官淋巴滤泡生分布于外周淋巴器官淋巴滤泡生 发中心发中心发中心发中心 边缘区边缘区边缘区边缘区DC:DC:DC in non DC in non lymphoid tissue
7、 I Interstitial DC:DC:分布于实质器官间质毛细血管附近分布于实质器官间质毛细血管附近分布于实质器官间质毛细血管附近分布于实质器官间质毛细血管附近 郎格汉斯细胞郎格汉斯细胞郎格汉斯细胞郎格汉斯细胞:位于表皮和胃肠上皮部位位于表皮和胃肠上皮部位位于表皮和胃肠上皮部位位于表皮和胃肠上皮部位 DC in DC in body fluid 输入淋巴液中的输入淋巴液中的输入淋巴液中的输入淋巴液中的DCDC及外周血中的及外周血中的及外周血中的及外周血中的DCDCDendritic cell Origin,distribution and migration Bone marrow Pro
8、genitor Tissue immature DCLymphoid organs mature DCAgMigration Circulation immature DC2.Surface moleculesn nImmature DC are different from mature DC in phenotypen nDC characteristics:DC characteristics:Morphology Morphology Expressing high level of MHC II Expressing high level of MHC II molecule and
9、 other co-stimulating molecule and other co-stimulating molecules.molecules.Extravasate to other lympho organ Extravasate to other lympho organ Initiate activation of nave T Initiate activation of nave T cellcelln nDC surface markers:DC surface markers:髓系髓系DCDC：以以CD11CD11、CD11CD11、CD13CD13，CDCD为标为标志
10、志 人淋巴样人淋巴样DCDC：CD11cCD11c/CD123+/BDCA2+/CD45RA+/CD4+/CD123+/BDCA2+/CD45RA+/CD4+人人DCDC主要特征性表面标志：主要特征性表面标志：CD1CD1，CD11CD11，CD83CD83 小鼠小鼠DCDC特异性标志：特异性标志：D1D1，NLDC145NLDC145Functions of DC 1.Interface of innate and adaptive immunity 1.Interface of innate and adaptive immunity Immature DC-Unspecific anti
11、gen uptake Immature DC-Unspecific antigen uptake Phagocytosis on the basis of recognitionPhagocytosis on the basis of recognition MacropinocytosisMacropinocytosis Mature DC-Antigen processing and Mature DC-Antigen processing and presentation.presentation.2.Involved in immune tolerance and immune 2.I
12、nvolved in immune tolerance and immune memory.memory.3.Cytokine secretion.3.Cytokine secretion.Monocytesn n组成组成组成组成:骨髓内的前单核细胞骨髓内的前单核细胞骨髓内的前单核细胞骨髓内的前单核细胞 外周血中的单核细胞外周血中的单核细胞外周血中的单核细胞外周血中的单核细胞 组织内的巨噬细胞组织内的巨噬细胞组织内的巨噬细胞组织内的巨噬细胞 n n功能功能功能功能:吞噬杀伤病原微生物吞噬杀伤病原微生物吞噬杀伤病原微生物吞噬杀伤病原微生物 抗原提呈抗原提呈抗原提呈抗原提呈 调节免疫应答调节免疫应
13、答调节免疫应答调节免疫应答 参与炎症，组织修复及组织再生参与炎症，组织修复及组织再生参与炎症，组织修复及组织再生参与炎症，组织修复及组织再生 B celln n抗原提呈抗原提呈:通过通过BCR特异性识别，结合特异性识别，结合并内化抗原，在低浓度可溶性抗原的提并内化抗原，在低浓度可溶性抗原的提呈中起重要作用呈中起重要作用n n参与体液免疫应答参与体液免疫应答n n 第二节第二节第二节第二节 抗原的处理与提呈抗原的处理与提呈抗原的处理与提呈抗原的处理与提呈Antigen processing and presentingn nDegradation of antigens by one of tw
14、o Degradation of antigens by one of two pathways yielding antigenic peptides that are pathways yielding antigenic peptides that are displayed bound to MHC molecules on the displayed bound to MHC molecules on the surface of antigen-presenting cellssurface of antigen-presenting cellsn nDifferent antig
15、en-processing and presentation pathwaysn nEndogenous antigensEndogenous antigens(those generated within the (those generated within the cell)are processed in the cell)are processed in the cytosolic pathwaycytosolic pathway and and presented on the membrane with presented on the membrane with class I
16、class I MHC MHC molecules;molecules;n nexogenous antigensexogenous antigens(those taken up by (those taken up by endocytosis)are processed in the endocytosis)are processed in the endocytic endocytic pathwaypathway and presented on the membrane with and presented on the membrane with class IIclass II
17、 MHC molecules MHC moleculesn nThe cytosolic pathway The cytosolic pathway n nPeptides for presentation are generated by protease Peptides for presentation are generated by protease complexes called proteasomes in the cytosolcomplexes called proteasomes in the cytosoln nTAP(transporter associated wi
18、th antigen TAP(transporter associated with antigen processing)mediates tranportation of processing)mediates tranportation of peptides generated in the cytosol into the RER peptides generated in the cytosol into the RER n nPeptides assemble with class I MHC within RERPeptides assemble with class I MH
19、C within RERn nClass I molecules loaded with peptide exit from the Class I molecules loaded with peptide exit from the RER,and proceed to the cell surface via the Golgi RER,and proceed to the cell surface via the Golgi complexcomplex内源性抗原加工，处理及提呈内源性抗原加工，处理及提呈n nThe endocytic pathwayThe endocytic pat
20、hwayn nPeptides are generated from internalized molecules in Peptides are generated from internalized molecules in endocytic vesiclesendocytic vesiclesn nIn RER,class II MHC molecules are assembled with In RER,class II MHC molecules are assembled with the invariant chain(Li)which guides the the inva
21、riant chain(Li)which guides the transportation of class II MHC molecules to endocytic transportation of class II MHC molecules to endocytic vesiclesvesiclesn nPeptides assemble with class II MHC molecules by Peptides assemble with class II MHC molecules by displacing li chaindisplacing li chainn nOn
22、ce a peptide has bound,the peptide-class II Once a peptide has bound,the peptide-class II complex is transported to the plasma membranecomplex is transported to the plasma membrane外源性抗原加工，处理及提呈外源性抗原加工，处理及提呈n nCross-presentation of exogenous antigensn nIn certain cases,APCs may present exogenous In c
23、ertain cases,APCs may present exogenous antigen to cytotoxic T cells in the context of class I antigen to cytotoxic T cells in the context of class I MHC molecules.MHC molecules.n nPresentation of nonpeptide antigensn nThe nonpretein antigens are presented by The nonpretein antigens are presented by
24、 members of the CD1 family of nonclassical members of the CD1 family of nonclassical class I moleculesclass I moleculesn n 脂类抗原的脂类抗原的脂类抗原的脂类抗原的CD1CD1分子提呈分子提呈分子提呈分子提呈CD1CD1分子：分子：分子：分子：n n非经典非经典非经典非经典MHC IMHC I类分子类分子类分子类分子n n提呈抗原：提呈糖脂或脂类抗原供提呈抗原：提呈糖脂或脂类抗原供提呈抗原：提呈糖脂或脂类抗原供提呈抗原：提呈糖脂或脂类抗原供CD1CD1限制性限制性限制性限制性 T T细胞识别细胞识别细胞识别细胞识别n nCD1CD1限制性限制性限制性限制性T T细胞：细胞：细胞：细胞：CD4-CD8-T;TCRCD4-CD8-T;TCRT T 细胞，细胞，细胞，细胞，NKTNKT细胞等细胞等细胞等细胞等n nCD1CD1抗原提呈意义：在机体抗微生物感染和对抗原提呈意义：在机体抗微生物感染和对抗原提呈意义：在机体抗微生物感染和对抗原提呈意义：在机体抗微生物感染和对 脂类抗原的应答中起重要作用脂类抗原的应答中起重要作用脂类抗原的应答中起重要作用脂类抗原的应答中起重要作用