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研究生:王大維
研究生(外文):Dah-Wei Wang
論文名稱:骨髓樹突狀細胞可藉吞噬己吃噬組織胞漿菌之巨噬細胞而活化專一性T淋巴球
論文名稱(外文):Bone Marrow-Derived Dendritic Cells can Stimulate Specific T lymphocytes by Phagocytosing Macrophage with Internalized Histoplasma capsulatum
指導教授:伍安怡
指導教授(外文):Betty Wu-Hsieh
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:免疫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
中文關鍵詞:樹突狀細胞噬細胞組織胞漿菌
外文關鍵詞:Dendritic cellmacrophagehistoplasma capsulatum
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個體感染組織胞漿菌 (Histoplasma capsulatum) 之初期,由於吞噬Histoplasma的噬細胞 (macrophage) 尚未被活化,故Histoplasma會以酵母菌的型式在噬細胞中生長繁殖。在活體外 (in vitro) 培養實驗中,Histoplasma的生長不會被未活化的噬細胞所抑制,反而因不斷增生而使寄主細胞死亡。Histoplasma的抗原是如何呈獻給T細胞?是否其它的抗原呈獻細胞 (antigen presenting cell) 也參與其中扮演重要角色。在本論文中,我們嘗試探討骨髓樹突狀細胞 (Dendritic cell) 是否可以吞噬因胞內菌繁殖而死亡的噬細胞,並呈獻抗原給T細胞。我們的實驗結果顯示小鼠骨髓樹突狀細胞可以直接吞噬Histoplasma並表現其抗原來刺激特異性T細胞,這些骨髓樹突狀細胞還可以吞噬己吃噬Histoplasma的噬細胞來獲取、呈獻,活化特異性的T細胞。樹突狀細胞經由直接吞噬Histoplasma或藉吞噬因胞內菌繁殖而死亡的噬細胞以活化的特異性T細胞均可增殖並產生IFN-。此外,利用細胞內免疫螢光染色可發現主要分泌IFN-gamma的T細胞都為CD4+。因此由本論文中可得知DC可以藉直接吞噬Histoplasma或是藉吞噬已吃噬Histoplasma的噬細胞來獲取、呈獻,活化特異性的T細胞分泌IFN-gamma及增殖。
Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of macrophage. In vitro, the yeast form of the fungus can survive and replicate within the un-activated macrophage. However, the resting macrophages are killed by the replicating yeast. In this study we wish to determine whether dendritic cells (DCs) could phagocytose the dead macrophage and present Hc antigen as APC. DCs were enriched by culturing mouse bone marrow cells in the presence of GM-CSF containing culture supernatant. 80% of cells expressed CD11c for 8 days culture. The enriched DCs were then cultured with peritoneal macrophage that has internalized viable or heat-killed yeasts. Electron microscopy revealed that the macrophages were killed by the replicating yeasts. DCs could phagocytose the dying cells and stimulate Hc-specific T lymphocytes proliferate and to secret IFN-gamma. Moreover, Intercellular IFN-gamma staining showed that CD4 T cells might be activated by DCs. We demonstrated in this study that DC could phagocytose yeast directly or dying macrophages with internalized pathogen and stimulate specific T lymphocyte.
中文摘要…………………………………………………………………… I
英文摘要…………………………………………………………………… II
第一章 緒論
第一節 全身組織胞漿菌簡介及噬細胞之相互關係…………………………1
第二節 樹突狀細胞在免疫反應中的角色……………………………………3
第三節 樹突狀細胞在組織胞漿菌感染上的相關研究………………………6
第四節 研究目標及實驗設計…………………………………………………9
第二章 實驗方法及材料
第一節 基本實驗方法……………………………………………………… 10
第二節 樹突狀細胞特徵分析……………………………………………… 17
第三節 細胞增殖反應分析………………………………………………… 19
第四節 酵素連結免疫吸附分析法………………………………………… 21
第五節 細胞內免疫螢光染色分析………………………………………… 23
第六節 穿透式電子顯微鏡切片觀察……………………………………… 26
第七節 實驗材料藥品及儀器……………………………………………… 27
第三章 研究結果
第一節 骨髓分化之樹突狀細胞分析……………………………………… 34
第二節 nylon wool純化T細胞分析…………………………………………35
第三節 樹突狀細胞表現組織胞漿菌抗原功能…………………………… 35
第四節 樹突狀細胞可藉吞噬已吃噬組織胞漿菌的巨噬細胞而刺激特異性T細胞 ………………………………………………………………………… 37
第五節 DC活化分泌IFN-gamma的T細胞種類……………………………… 40
第四章 討論……………………………………………………………… 41
第五章 圖表與說明………………………………………………………… 46
第六章 參考文獻…………………………………………………………… 75
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