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研究生:翁育詩
研究生(外文):Yu-Shi Weng
論文名稱:肺炎雙球菌細胞壁成份對於抗原呈現分子及T細胞輔助效應的影響
論文名稱(外文):The Influence of Streptococcus Pneumoniae Cell Wall Components on Antigen Presenting Molecules and T Helper Response
指導教授:劉德勇劉德勇引用關係
指導教授(外文):Teh-Yung Liu, Ph.D.
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生化科學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:1999
畢業學年度:87
語文別:英文
論文頁數:57
中文關鍵詞:肺炎雙球菌細胞壁抗原呈現分子T細胞輔助效應類神經細胞脂台口酸台口酸專一性抗原辨認反應
外文關鍵詞:Streptococcus PneumoniaeAntigen presentating moleculeT helper responseDendritic CellLipoteichoic acidTeichoic acidAntigen specific responseCD 1
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免疫防禦是宿主與病原間的生存競逐.為主動奪得防禦優勢,宿主不惜發動急性發炎反應, 如釋放NO- ,等自由基(Free redical), 採取全面狙殺的方式,以阻止入侵者的擴張.然而在正常防衛中,這樣的浩劫並不會蔓延,因為過於激烈的獵殺會伴隨如自體免疫(Autoimmune response)的發生.而通常對於無法一時殲滅的病原,免疫防禦會轉向較智慧的專一性抗原辨認反應,並催動辨認防禦的集中.(Antigen Specific Response)其中的機制包括由抗原表現細胞(Antigen Presentating Cell)所進行的抗原呈現(Antigen Presentation)和經由訊息傳遞所造成的輔助T 細胞活化(T helper cell Activation).
由防禦效率而言,一般認為宿主對於細菌細胞壁的成分多採取發炎反應,但若細菌長期倖存宿主又會採取什麼策略?這機制在以蛋白質為抗原的免疫研究上已建構一些具體的輪廓,然而於非蛋白質的抗原卻鮮為研究,伴隨CD1在醣脂抗原呈現上的新發現, 在此我們依循這幾年的科學線索,以結構已被詳定的肺炎雙球菌(Streptococcus pneumoniae)細胞壁探索其於抗原辨認分子(Antigen Presenting molecule)與輔助T 細胞(Th cells)活化的關係.而我們以巨噬細胞(Macrophage)與類神經細胞(Dendritic Cells)為觀察抗原呈現分子的標的,接著研究肺炎雙球菌細胞壁成分對於輔助 T細胞的活化與極化效應(Activation and Polarization),並進而觀察抗原呈現分子在其中所扮演的角色.
C-聚糖脂,台口酸,脂台口酸都是多醣或醣脂成份,均是肺炎雙球菌細胞壁成分.於實驗中,發現脂台口酸(Lipoteichoic acid )會分別於6小時後提高巨噬細胞與類神經細胞上CD1分子的表現,而C-聚糖(C-polysaccharide)則引起巨噬細胞上MHC class I 分子的增加,其他的抗原呈現分子則無明顯變化.訝異的是這些成份在活體內與活體外,竟都會引起Th1 反應.在研究肺炎雙球菌細胞壁成分刺激巨噬細胞與類神經細胞後抗原呈現分子對於Th response 的影響時,也發現若使用抗MHC class I,II 與CD1抗體的抑制會降低脂台口酸(Lipoteichoic acid )刺激下的輔助T 細胞分泌INF- γ,而.在以類神經細胞與T 細胞共培養的脂台口酸中,抗CD1d抗體對於降低輔助T 細胞分泌INF- γ的程度較其他二種顯著, 相對於此現象,在巨噬細胞,T細胞與脂台口酸共培養時,影響較大的則是MHC class II分子,其次才是CD1d 分子. 而在以台口酸刺激的DC-T共培養實驗中,CD1 則無顯著變化.

Protein antigens have been broadly investigated in antigen-specific immune response, which involved the process of antigen presentation and effector response mediated by CD4+ T cells. Nonpeptide antigens, such as glycans and glycolipids, however, are less studied. With the discovery of CD1 molecules, the nonpeptide antigens have enlisted newly found interest in this field of study.
The structure of the nonpeptide antigens of the Pnuemococcal (Streptococcus pneumoniae) cell wall, such as lipoteichoic acid (LTA), teichoic acid (TA) and C-polysaccharide have been well studied in 1990s. We took these glycans or lipoglycans that have defined structure to study the role of nonpeptide antigens in cell-mediated immune response as well as their relationship with dendritic cells (DCs), a novel antigen presenting cell (APC) that has drawn a great deal of attention in recent studies.
In the present study, we found that LTA, TA, and C-polysaccharide could elicit Th1 responses. With its lipid anchor, LTA elevated CD 1 on DCs and macrophages; whereas, C-polysaccharide increased MHC class I response on macrophages. LTA and TA stimulated DCs were demonstrated to prime naive T cells and to initiate Th1 responses as seen in studies using peptide antigens. To summarize this study, pnuemococcal cell wall nonpeptide antigens could induce antigen-specific effector (Th) response through antigen stimulated DCs.

Abbrevation 1
Chinese Abstract 2
Abstract 3
Introduction 4
Material and Methods 13
Result 19
Discussion 24
Tables 28
Figures 29
References 53

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