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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊宏志 | |
| dc.contributor.author | Sung-Hsiang Jui | en |
| dc.contributor.author | 芮嵩翔 | zh_TW |
| dc.date.accessioned | 2021-06-16T23:48:09Z | - |
| dc.date.available | 2014-09-19 | |
| dc.date.copyright | 2012-09-19 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-23 | |
| dc.identifier.citation | 1. Palese P. Differences in RNA patterns of influenza A viruses. Journal of Virology. 1976.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65521 | - |
| dc.description.abstract | 流感病毒自1918年的西班牙流感以來，已經造成數次的大流行，最近一次是2009年新型流感的大流行，造成大流行的流感病毒能迅速在全世界傳播，並造成許多重症或致死病例現今的流感疫苗，以不活化的病毒為主，能刺激免疫系統中的B 細胞產生辨認病毒外鞘蛋白質的中和抗體，並有效的預防相同或極為相似的病毒株的感染，但由於流感病毒其抗原易於突變，包括抗原飄移與抗原移型，使得目前使用的誘發B細胞免疫力的疫苗則無法有效預防新的流感病毒株的感染並阻止疫情擴散。
由於T 細胞免疫系統可以辨認病毒的內部蛋白質，造成其在不同株的病毒間有跨株保護的效果，因此如何能夠在流感病毒感染後建立一個良好的且持久的記憶性T細胞免疫系統，是我們所好奇的，而調節性T細胞能影響T細胞免疫力及記憶T細胞的產生，此外，它對於T細胞的擴張，縮減以及記憶三個過程都具有可能的影響效果，也有研究指出調節性T細胞對於T細胞的二次反應具有影響。近年來有研究指出在急性病毒感染之下的確會有調節性T細胞的出現，此外，有研究表示在肺中不斷地以能產生氣喘的抗原刺激後，可以造成調節性T細胞的表現量上升，然而在此所表現出的調節性T細胞並沒有區分究竟是認自身抗原的自然性調節T細胞或是認外來抗原的誘發性調節T細胞，因為誘發性調節T細胞目前在免疫中所扮演的角色比較不明，因此我們對於具有抗原專一性的誘發性調節T細胞非常有興趣，在之前的研究中發現特別是若以低劑量的抗原刺激或避免誘發太強的免疫反應，會造成具有抗原專一性的調節性T細胞的擴增，事實上，在流感的季節，我們有可能反覆接觸到低劑量的流感病毒，因此，我們假設以低劑量的流感病毒重複感染一個個體後,會產生並擴增具有流感病毒抗原專一性的調節性T細胞並抑制之後接續感染不同株流感病毒所誘發的T細胞免疫力，我們初步的研究成果顯示，CD4+FoxP3+調節性T細胞在急性流感病毒感染後確實會在肺部及肺的沖洗液有上升的現象，不過目前並不知道這些上升的調節性T細胞是先天性調節性T細胞或誘發調節性T細胞最後我們設計了幾個實驗方式來看低劑量的流感病毒重複感染一個個體後， 是否會產生調節性T細胞並對T細胞免疫系統造成影響，而在我們的實驗中也確實發現了若是小鼠有先重複感染低劑量的HKx31病毒株，之後再感染高劑量的PR8病毒株，相對於對照組對流感病毒專一辨認的T細胞數目確實有下降的現象， 不過究竟調節性T細胞是否在其中扮演著什麼樣的角色，我們還需要更深入的探討。 | zh_TW |
| dc.description.abstract | Since the outbreak of Spanish flu in 1918, there have been several pandemics of influenza A virus. The latest one is the pandemic of 2009 H1N1 influenza A virus. Pandemic influenza A virus usually spreads rapidly across the world, and causes significantly higher morbidity and mortality than seasonal flu virus does. Current influenza virus vaccine can induce robust neutralizing antibody, and effective prevent infection by the same or closed related strain of influenza virus. However, due to high mutation rate of influenza virus, B cell vaccine fails to cope with the emergence of a new strain of influenza virus.
T cells can recognize conserved internal proteins of influenza virus. T cell immunity can provide a “cross-protective” immunity across a broad-spectrum strains of influenza virus. Therefore, we focus on the study of T cell immunity against influenza virus. To establish effective T cell immunity, it is important to understand the factors that affect the generation and maintenance of memory T cell response. Regulatory T cells (Tregs) can regulate T cell immunity, and affect the establishment of T cell memory. Recently, Tregs have been reported to influence T cell immunity induced by acute viral infection and accumulate in the infection site. Besides, Tregs increase in the lung following repeated challenge with antigens. Particularly, low-dose antigen or suboptimal immune stimulation induce more antigen-specific Tregs. Actually, it is possible an individual may have a chance to repeatedly encounter low-dose influenza virus. Therefore, we hypothesize that repeated infection of low-dose influenza virus can induce antigen-specific Tregs, and may suppress the T cell immunity induced by subsequent acute influenza virus infection. Our preliminary result showed that the frequency of CD4+Foxp3+ T cells increased in lung and brochoalveolar lavage (BAL) after acute influenza virus infection. However, we currently do not know whether these influenza virus-induced Tregs are nTregs or influenza virus antigen-specific Tregs. Finally, in a priming and challenge protocol of repeated infection of low-dose influenza virus revealed that, in mice repeatedly primed with low-dose HKx31 strain, the frequency of the influenza virus antigen-specific T cells was reduced after the subsequent challenge with high-dose PR8 strain. However, whether antigen-specific Tregs contribute to this outcome remains further investigating. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T23:48:09Z (GMT). No. of bitstreams: 1 ntu-101-R99445114-1.pdf: 4948320 bytes, checksum: 978c1c580d6aac9045669aff8262997c (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | TABLE of CONTENTS
中文摘要 i Abstract iii 1. INTRODUCTION 1 1.1 Influenza virus 1 1.1.1 Evolutionary strategies of influenza 2 1.1.2 THE IMPORTANCE OF T CELL IN INFLUENZA INFECTION 4 1.2 Regulatory T cell 6 1.2.1 Natural Treg 6 1.2.2 Inducible Treg 7 1.2.3 iTreg induced by acute infection 8 1.2.4 iTregs induced by low-dose antigens 9 1.2.5 iTreg induced by repeatedly exposure to antigen 10 1.3 T cell immunity 11 1.3.1 T cell memory 12 1.3.2 The effect of Tregs on memory T cells 13 1.4 Lung 14 1.4.1 The immune system of lung 14 1.4.2 The role of Tregs in lung 15 1.5 The role of antigen-specific Tregs induced by repeatedly low-dose influenza infection in T cell immunity 16 2. AIM 18 3. MATERIALS AND METHODS 19 3.1 Mice 19 3.2 Cell lines and cell culture 19 3.3 Virus 20 3.4 Reverse genetics 21 3.5 Plaque assay 22 3.6 Intranasal infection of mice with influenza A virus 22 3.7 Cell preparation and purification 23 3.8 Generation of bone marrow derived dendritic cell 23 3.9 Assessment of T cell immunity 25 3.10 Flow cytometry 25 3.10.1 Antibody used in flow cytometry 25 3.10.2 Staining of antibody 26 3.10.3 Staining of pentamer 27 4. RESULTS 28 4.1 Dose response of PR8 and HKx31 influenza A virus infection in mice. 28 4.2 Kinetics of Tregs in different tissues following acute influenza A virus infection. 29 4.3 The effects of repeated infection with low-dose influenza A virus on the expansion of Tregs 30 4.4 The effects of repeated infection with low-dose influenza A virus on the frequency of influenza antigen-specific effector T cells. 31 5. DISCUSSIONS 34 5.1 The existence of viral antigen-specific Tregs following acute influenza virus infection 34 5.2 the establishment of priming and challenge protocol in induction of Ag-specific Tregs 35 5.3 Whether there are regulatory mechanisms other than viral antigen-specific Tregs in control of effector CD8 T cell immunity in the influenza virus priming-challenge mouse model 40 5.4 Investigating the role of antigen-specific Tregs in this priming and challenge mouse model 41 6. FIGURES 45 7. REFERENCE 59 LIST of FIGURES Figure 1. The Generation of PR8 an HKx31 using reverse genetics. 45 Figure 2. Dose response of PR8 in CB57L/6 mice. 46 Fig 3. Dose response of HKx31 virus in CB57L/6 mice. 47 Fig 4. The dynamics of Tregs during infection of PR8 and HKx31. 48 Fig 5. The mice primed with lower dose of PR8 and challenged with high-dose PR8 (Protocol A) 49 Figure 6. The body weight loss of the mice primed with low-dose PR8 in different intervals and challenged with high-dose HKx31 (Protocol B) 51 Figure 7. The frequency of IFN-γ-producing CD8+ T cells after challenge with high-dose virus in Protocol B-1 and B-2. 52 Figure 8. Decrease of thefrequency of influenza virus-specific CD8+ T cells after the high-dose virus challenge in the mice repeatedly primed with low-dose virus. 55 Figure 9. The hypothetical model for induction of influenza virus antigen-specific Tregs during repeated infection of low-dose influenza virus. 57 | |
| dc.language.iso | en | |
| dc.subject | 調節性T細胞 | zh_TW |
| dc.subject | 流感 | zh_TW |
| dc.subject | 低劑量 | zh_TW |
| dc.subject | 重複感染 | zh_TW |
| dc.subject | T細胞免疫力 | zh_TW |
| dc.subject | repeated infection | en |
| dc.subject | T cell immunity | en |
| dc.subject | regulatory T cell | en |
| dc.subject | influenza | en |
| dc.subject | low dose | en |
| dc.title | 重複性低劑量流感病毒的感染對調節性T細胞生成及T細胞免疫系統的影響 | zh_TW |
| dc.title | The effect of repeated infection of low-dose influenza virus on induction of regulatory T cells and establishment of T cell immunity | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林素珍,江伯倫,陶秘華 | |
| dc.subject.keyword | 調節性T細胞,流感,低劑量,重複感染,T細胞免疫力, | zh_TW |
| dc.subject.keyword | regulatory T cell,influenza,low dose,repeated infection,T cell immunity, | en |
| dc.relation.page | 71 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-07-23 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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