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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 莊雅惠(Ya-Hui Chuang) | |
dc.contributor.author | Hsiao-Yu Jen | en |
dc.contributor.author | 任曉玉 | zh_TW |
dc.date.accessioned | 2021-05-20T21:55:14Z | - |
dc.date.available | 2013-09-13 | |
dc.date.available | 2021-05-20T21:55:14Z | - |
dc.date.copyright | 2010-09-13 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-07-27 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10747 | - |
dc.description.abstract | 過敏性紫斑症 (Henoch-Schonlein Purpura; HSP) 是孩童常見的全身性微血管發炎之自體免疫疾病。在體液性免疫方面,急性期病人的血清IgA升高,TNF-α、IL-6、IL-8、TGF-β與VEGF亦升高,且出現多種IgA 自體抗體 (IgA autoantibodies),但在細胞免疫方面的研究則相當缺乏。此外,目前亦無動物模式可用於研究其致病機轉。在本研究探討T helper (Th)1與Th17 cells之角色及嘗試破除免疫耐受性以建立自體免疫疾病之小鼠模式。
第一部分 探討過敏性紫斑症中Th1與Th17 cells之角色 Th1與Th17 cells之角色在許多自體免疫疾病已被證實。在此我們探討Th1與Th17 cells在過敏性紫斑症之角色。首先我們測病人血清中Th1與Th17相關細胞激素IL-17、IL-21、IL-23與IFN-γ之表現量。結果顯示,相較於正常對照組,急性期過敏性紫斑症病人血清中IL-17表現量顯著增加,但IFN-γ並無差異。此外,急性過敏性紫斑症病人之週邊血單核球IL-17-secreting T cells (Th17 cells)與上清液中IL-17含量均比緩解期時增加;然而IFN-γ-secreting T cells (Th1 cells)與上清液中IFN-γ則無明顯差異。由此推論,過敏性紫斑症可能是Th17主導的自體免疫疾病,而與Th1免疫反應較無相關。 第二部分 建立過敏性紫斑症小鼠動物模式 β2GPI被認為是過敏性紫斑症的自體抗原之一,在我們以注射human β2GPI (hβ2GPI)以建立小鼠疾病模式。將human β2GPI混合於佐劑以腹腔注射致敏小鼠。結果顯示,hβ2GPI混合於CFA/IFA中致敏小鼠,小鼠可產生高量之anti-mouse β2GPI (mβ2GPI)IgG,但anti-mβ2GPI IgA並無增加,病理檢驗結果亦未見血管發炎。再以hβ2GPI與先前研究證實可以提高血清IgA的Deoxynivalenol (DON)同時致敏小鼠仍然只能引起anti-mβ2GPI IgG,而無anti-mβ2GPI IgA。改以Alum當佐劑仍然無法引起小鼠anti-mβ2GPI IgA反應。綜合言之,注射human β2GPI可以打破免疫耐受性使小鼠產生anti-mouse β2GPI IgG,但仍需其他方法以引發IgA反應。 由本研究的結果得知,過敏性紫斑症可能是Th17主導的自體免疫疾病,而與Th1免疫反應較無相關。另外,注射human β2GPI可以打破小鼠免疫耐受性,若可建立此過敏性紫斑症之小鼠模式,則有利於後續更深入之研究。 | zh_TW |
dc.description.abstract | Henoch-Schonlein Purpura (HSP) is an autoimmune vasculitis that occurs mainly in childhood. At the acute stage of HSP, serum levels of IgA, TNF-α, IL-6, IL-8, TGF-β, and VEGF were increased. In addition, a number of studies report that several IgA autoantibodies are associated with HSP. However, there were no reports regarding cellular immunity in HSP and no HSP animal models so far to explore the mechanism of HSP. Herein, the aims of this study are to investigate the role of Th1 and Th17 cells in HSP and try to establish a mouse model of HSP.
Part I : The role of Th1 and Th17 cells in Henoch-Schonlein Purpura Recently, various studies demonstrated that Th1 and Th17 are important in the pathogenesis of several autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. The role of Th1 and Th17 cells has not been investigated in HSP. Therefore, the aim of this study is to examine the role of Th1 and Th17 cells in HSP. Our results demonstrated that serum levels of IL-17 were significantly elevated in patients with acute stage of HSP compared with healthy controls, whereas serum levels of IFN-γ remained unchanged. Furthermore, the percentage of Th17 cells and the cytokine levels of IL-17 were increased at the acute stage compared with those at the convalescent stage by using intracellular staining for Th1 and Th17 cell detection and ELISA for culture supernatant detection. However, the percentage of Th1 cells and IFN-γ expression were not elevated at the acute stage of HSP. These results suggested that IL-17 rather than IFN-γ play a crucial role in the pathogenesis of HSP. Part II : Establishment of mouse model of Henoch-Schonlein Purpura β2-glycoprotein I (β2GPI) are supposed to be an autoantigen of HSP because high levels of IgA anti-β2GPI antibodies were observed in patients with HSP. The specific aim of this study is to establish a mouse model of HSP. We firstly immunized naïve mice with human β2GPI (hβ2GPI) protein emulsified in adjuvant. Our results showed that hβ2GPI-immunized mice had elevated serum levels of anti-mβ2GPI IgG but not anti-mβ2GPI IgA. In addition, the biopsies have not seen inflammation in the wall of capillaries. To induce a high serum level of IgA, we used hβ2GPI and deoxynivalenol (DON), a mycotoxin can elevate serum IgA and mesangial IgA deposition in mice, or hβ2GPI emulsified in aluminum to immunize mice. However, the serum levels of β2GPI-specific IgA were not elevated in both strategies. In conclusion, our results demonstrated that IL-17 may play an important role in the pathogenesis of HSP. Moreover, establishment of the mouse model of HSP can provide the further study to determine the mechanism of HSP. | en |
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dc.description.tableofcontents | 致謝….. i
中文摘要 ii Abstract iv 縮寫對照表 vi 圖表目錄 x 第一章 總論 1 1.1 過敏性紫斑症 ( Henoch-Schönlein purpura;HSP )之背景介紹 1 1.2 免疫學上之病理特徵 1 1.3 細胞激素 (cytokine)在過敏性紫斑症中之作用 2 1.4 過敏性紫斑症疾病生成之假說 2 第二章 探討過敏性紫斑症之Th1與Th17 cells之角色 4 2.1 研究背景 4 2.1.1 Th1 cells及Th17 cells 4 2.1.2 Th1 cells與Th17 cells在自體免疫疾病中扮演之角色 5 2.2 研究目的 6 2.3 實驗材料與方法 6 2.3.1 病人檢體及對照組 6 2.3.2 由全血分離PBMC (Peripheral blood mononuclear cell) 6 2.3.3 以PBMC培養bulk T cells與體外刺激 (in vitro stimulation) 6 2.3.4 流式細胞儀 (flow cytometry)分析細胞表面與細胞內抗原 7 2.3.5 以Enzyme linked immunosorbent assay (ELISA)測量血清與 上清液細胞激素之濃度 7 2.3.6 繪圖及統計分析 8 2.4 結果 8 2.4.1 急性過敏性紫斑症病人血清中IL-17之表現量增加 8 2.4.2 急性期過敏性紫斑症病人之IL-17 secreting T cells與上清 液中Th17 cytokines之表現量上升 8 2.5 討論 9 第三章 建立過敏性紫斑症小鼠動物模式 12 3.1 研究背景 12 3.1.1 自體免疫疾病之定義 12 3.1.2 Autoantigen與過敏性紫斑症 13 3.1.3 β2-glycoprotein I (β2GPI)之簡介 13 3.1.4 佐劑 (Adjuvant;CFA/IFA及Aluminum) 15 3.1.5 嘔吐素(Deoxynivalenol DON;vomitoxin) 15 3.2 研究目的 15 3.3 實驗材料與方法 16 3.3.1 實驗用小鼠 16 3.3.2 hβ2GPI引發過敏性紫斑症小鼠模式之建立 16 3.3.3 血清樣品之收集 16 3.3.7 以ELISA測量血清中anti-hβ2GPI IgA或IgG 17 3.3.8 以ELISA測血清中total IgA 17 3.3.9 脾臟細胞 (splenocyte)之細胞增生 18 3.3.10 小鼠之病理切片 18 3.3.11 以E. coli表現蛋白系統表現小鼠β2GPI 18 3.3.12 SDS-PAGE蛋白質電泳 21 3.3.13 Coomassie blue staining 21 3.3.14 西方墨點法 (Western blotting assay) 21 3.3.15 繪圖及統計分析 22 3.4 結果 22 3.4.1 以E. coli表現蛋白系統表現小鼠β2GPI蛋白 23 3.4.2 以E. coli表現蛋白系統表現全長之小鼠β2GPI蛋白 23 3.4.3 以E. coli表現蛋白系統表現小鼠β2GPI片段蛋白 23 3.4.4 利用hβ2GPI引發過敏性紫斑症之小鼠模式之建立 23 3.4.5 利用hβ2GPI引發過敏性紫斑症小鼠模式之建立證明小鼠 產生anti-mouse immune response 25 3.4.6 利用hβ2GPI與DON引發過敏性紫斑症小鼠模式之建立 26 3.4.7 利用hβ2GPI與Alum引發過敏性紫斑症小鼠模式之建立 27 3.5 討論 27 第四章 總結 31 第五章 圖表 32 第六章 參考文獻 54 第七章 附錄 61 | |
dc.language.iso | zh-TW | |
dc.title | 探討過敏性紫斑症之Th1與Th17 cells之角色及建立小鼠動物模式 | zh_TW |
dc.title | The Role of Th1/Th17 Cells and Establishment of Mouse Model in Henoch-Schonlein Purpura | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 江伯倫(Bor-Luen Chiang),楊曜旭(Yao-Hsu Yang),胡忠怡(Chuang-Yi Hu) | |
dc.subject.keyword | 過敏性紫斑症,Th1 cells,Th17 cells,human β2GPI, | zh_TW |
dc.subject.keyword | HSP,Th1 cells,Th17 cells,human β2GPI, | en |
dc.relation.page | 66 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2010-07-27 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
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