抗原呈递细胞

1、Chapter 7 APC,Antigen presenting cell (APC) Definition APC is a cell that displays peptide fragment of protein antigens, in association with MHC molecules, on its surface and activates antigen-specific T cells. In addition to displaying peptide-MHC complexes, APCs must also express costimulatory mol

2、ecules to activate T lymphocytes optimally,T cells do not recognise native antigens,Y,Y,Y,Y,Y,Y,活化增殖、产生抗体,无增殖 无CK产生,BCR交联,Antigens must be processed in order to be recognised by T cells,T cell response,无应答,无应答,无应答,无应答,抗原加工、递呈,第一节 抗原提呈细胞的种类 Professionals APC: Dendritic cells Macrophages B cells,Non-p

3、rofessional APC ： 在某些活性分子刺激下能被诱导表达MHC-II类分子并能处理和提呈抗原的细胞 。包括：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。 广义APC：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,Classification and distribution DC in lymphoid tissue : Interdugutating DC: 分布于淋巴组织胸腺依赖区和次级淋巴组织 Folliculus DC: 分布于外周淋巴器官淋巴滤泡生 发中心 边缘区DC: DC in non lymphoid tissu

4、e Interstitial DC: 分布于实质器官间质毛细血管附近 郎格汉斯细胞: 位于表皮和胃肠上皮部位 DC in body fluid 输入淋巴液中的DC及外周血中的DC,Dendritic cell Origin, distribution and migration,2. Surface molecules Immature DC are different from mature DC in phenotype,DC characteristics: Morphology Expressing high level of MHC II molecule and other co-

5、stimulating molecules. Extravasate to other lympho organ Initiate activation of nave T cell,DC surface markers: 髓系DC： 以CD11、CD11、CD13，CD为标志 人淋巴样DC： CD11c/CD123+/BDCA2+/CD45RA+/CD4+ 人DC主要特征性表面标志： CD1，CD11，CD83 小鼠DC特异性标志：D1，NLDC145,Functions of DC 1. Interface of innate and adaptive immunity Immature

6、DC-Unspecific antigen uptake Phagocytosis on the basis of recognition Macropinocytosis Mature DC -Antigen processing and presentation. 2. Involved in immune tolerance and immune memory. 3. Cytokine secretion,Monocytes,组成: 骨髓内的前单核细胞 外周血中的单核细胞 组织内的巨噬细胞 功能: 吞噬杀伤病原微生物 抗原提呈 调节免疫应答 参与炎症，组织修复及组织再生,B cell,抗

7、原提呈: 通过BCR特异性识别，结合并内化抗原，在低浓度可溶性抗原的提呈中起重要作用 参与体液免疫应答,第二节 抗原的处理与提呈,Antigen processing and presenting,Degradation of antigens by one of two pathways yielding antigenic peptides that are displayed bound to MHC molecules on the surface of antigen-presenting cells,Different antigen-processing and presenta

8、tion pathways Endogenous antigens (those generated within the cell) are processed in the cytosolic pathway and presented on the membrane with class I MHC molecules; exogenous antigens (those taken up by endocytosis) are processed in the endocytic pathway and presented on the membrane with class II M

9、HC molecules,The cytosolic pathway Peptides for presentation are generated by protease complexes called proteasomes in the cytosol TAP (transporter associated with antigen processing) mediates tranportation of peptides generated in the cytosol into the RER Peptides assemble with class I MHC within R

10、ER Class I molecules loaded with peptide exit from the RER, and proceed to the cell surface via the Golgi complex,内源性抗原加工，处理及提呈,The endocytic pathway Peptides are generated from internalized molecules in endocytic vesicles In RER, class II MHC molecules are assembled with the invariant chain (Li) wh

11、ich guides the transportation of class II MHC molecules to endocytic vesicles Peptides assemble with class II MHC molecules by displacing li chain Once a peptide has bound, the peptide-class II complex is transported to the plasma membrane,外源性抗原加工，处理及提呈,Cross-presentation of exogenous antigens In certain cases, APCs may present exogenous antigen to cytotoxic T cells in the context of class I MHC molecules,Presentation of nonpeptide antigens The nonpretein antigens are presented by members