【正文】 But 第六十七頁，共六十七頁?！?1〕淋巴干細胞向中樞淋巴器官的歸巢。主要結(jié)合粒細胞譜系 ,此外還結(jié)合 NK、 B和 CD8+T細胞。 內(nèi)容總結(jié) 白細胞分化抗原和黏附分子。s novel mechanism is unknown, but it is thought to work by reducing the immune system39。 FTY720indeuced inhibition of T cells egress from lymph node 第六十五頁，共六十七頁。 blood thymus, spleen S1P1 S1P S1P lyase radiation resistant cells RBC lymph lymph node, Peyer’s patch S1P1 S1P S1P lyase radiation resistant cells Lymphocytes express S1P1 and exit lymphoid ans in response to S1P ? S1P is abundant in blood and lymph ? RBC major source of blood S1P ? Lymphatic endothelial cells are source of lymph S1P ? Extracellular S1P is kept low inside lymphoid tissue ? S1P1 is a point of egress control Lymphatic Endothelial cells 第六十三頁，共六十七頁。 Sphingosine 1phosphate (S1P) ? Abundant in plasma (~1uM) and lymph (~) ? Made intracellulary by all cell types during sphingolipid degradation but only secreted by some cell types ? Ligand for a family of Gprotein coupled receptors (S1P15, formerly known as EDG receptors) ? S1P receptors have roles in blood vessel and heart development Sphingosine S1P Ethanolamine + Hexadecanal SphK S1P phosphatase S1P lyase S1P1 (edg1) S1P2 (edg5) S1P4 (edg6) S1P5 (edg8) S1P3 (edg3) 第六十一頁，共六十七頁。 Chiba et al. “ FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats〞 J Immunol (1998) Days after FTY720 administration mg/kg mg/kg Also shown by Yagi H et al., to inhibit thymocyte emigration from the thymus. Eur J Immunol. (2024) TDL,thoracic duct lymph 第五十九頁，共六十七頁。 How do cells exit from lymphoid tissues? MEDULLARY SINUSES 第五十七頁，共六十七頁。淋巴細胞再循環(huán)有利于識別抗原和迅速傳遞信息，使分散各處的淋巴細胞成為一個相互關(guān)聯(lián)的有機整體，使功能相關(guān)的淋巴細胞共同進行免疫應答。 第五十五頁，共六十七頁。 The animation The Players 第五十三頁，共六十七頁。 ADAM (A Disintegrin And Metalloproteinase) A unified schematic view of paracellular transendothelial migration. 第五十一頁，共六十七頁。 第四十九頁，共六十七頁。ve B CXCR5, CXCR4, CCR7 BLC, SDF1, SLC Th1 effector CCR2, CCR5, CXCR3 MIP1?, MCP1, RANTES, IP10 Th2 effector CCR3, CCR4, CCR8 Eotaxin, MDC, TARC, I309 CD8 effector CCR2, CCR5, CXCR3 MCP1, MIP1a, RANTES, IP10 Immature DC CCR1,2,3,4,5,6 MCP1, 2, 3, 5, RANTES, MIP1? (see Zlotnik and Yoshie, Immunity 12, 121 (2024) for standardized chemokine nomenclature) Other chemoattractants: monocytes, neutrophils are attracted by C5a, fMLP, PAF Th2 cells, eosinophils, basophils express CRTH2, a receptor for prostaglandin D2 第四十七頁，共六十七頁。 Chemokines in Inflammation The large number of chemokines and chemokine receptors allows for a significant amount of homing specificity to be imparted by these molecules Examples: (PARTIAL LIST) Cell type Chemokine Receptors Ligands Neutrophils CXCR1, CXCR2 IL8, GCP2, Gro? Eosinophils CCR1, CCR3 Eotaxin, MIP1?, MCP3 Monocytes CCR1, CCR2, CCR5 MCP1, 2, 3, 5, RANTES, MIP1? Na239。 Neutrophil extravasation in inflammation Blood flow 第四十五頁，共六十七頁。 Inflammation ? involves local release of cytokines and chemokines by tissue cells in response to pathogen products or damage ? cytokines cause increase in vascular permeability leading to local swelling, increased entry of antibody, plement, etc. ? cytokines cause increased expression of adhesion molecules on vascular endothelium and these work together with chemokines to recruit cells neutrophils, monocytes, NK cells and, later, effector lymphocytes 第四十三頁，共六十七頁。 Homing and Inflammation 第四十一頁，共六十七頁。 淋巴細胞歸巢過程的分子根底是淋巴細胞與各組織、器官血管內(nèi)皮細胞粘附分子的相互作用。 第四十頁，共六十七頁。 鈣黏素分子的根本結(jié)構(gòu) 粘蛋白樣家族 粘蛋白樣家族〔 mucinlike family〕屬新歸類的一類細胞粘附分子。 鈣粘素家族 鈣粘素〔 cadh