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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 微生物學科所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7891
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dc.contributor.advisor賈景山(Jean-San Chia)
dc.contributor.authorChia-Hsin Chengen
dc.contributor.author鄭佳欣zh_TW
dc.date.accessioned2021-05-19T17:57:31Z-
dc.date.available2021-08-26
dc.date.available2021-05-19T17:57:31Z-
dc.date.copyright2016-08-26
dc.date.issued2016
dc.date.submitted2016-08-12
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50. Czaikoski, P.G., et al., Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis. PLoS One, 2016. 11(2): p. e0148142.
51. Martinod, K., et al., Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci U S A, 2013. 110(21): p. 8674-9.
52. Rabadi, M.M., et al., Peptidyl arginine deiminase-4 deficient mice are protected against kidney and liver injury after renal ischemia and reperfusion. Am J Physiol Renal Physiol, 2016: p. ajprenal.00254.2016.
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54. Hoshino, T., et al., Novel epitopic region of glucosyltransferase B from Streptococcus mutans. Clin Vaccine Immunol, 2011. 18(9): p. 1552-61.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7891-
dc.description.abstract感染可能引發風溼熱、吉蘭-巴雷氏症狀群等自體免疫疾病。本實驗室先前的研究指出,感染性心內膜炎及擴散性全身性感染患者體內含有抗雙股去氧核糖核酸抗體。當大鼠經由靜脈感染轉糖鏈球菌後,體內會產生抗雙股去氧核糖核酸抗體。脾臟對於清除血液中的細菌及產生抗體扮演一定的角色;因此,我們假設血液中的細菌可能引發脾臟產生自體抗體。我們發現,當小鼠經由靜脈感染後,在5至7天內能產生抗雙股去氧核糖核酸抗體;利用脾臟被切除的小鼠進行同樣的實驗,發現小鼠體內抗雙股去氧核糖核酸抗體的量下降,顯示血液中的細菌能促使脾臟產生自體抗體。我們發現純化的抗雙股去氧核糖核酸抗體和轉糖鏈球菌的表面蛋白: 葡餹基轉移酶B有交叉反應。另外,紅斑性狼蒼患者體內通常具有大量的抗雙股去氧核糖核酸抗體,我們發現有一種核醣體蛋白: L7/L12在紅斑性狼蒼患者體內可能無法誘發產生抗雙股去氧核糖核酸抗體。以上結果顯示血液循環系統中的細菌感染能使脾臟產生自體抗體,而葡餹基轉移酶B及L7/L12可能產生交叉反應促使自體抗體的產生。zh_TW
dc.description.abstractInfections play roles in the induction of autoimmune diseases, including rheumatic fever and Guillain–Barré syndrome. Our previous data showed that autoantibodies such as anti-dsDNA antibodies can be found in patients with infective endocarditis and disseminated systemic infection. The anti-dsDNA antibodies can be induced in rat intravenously infected with Streptococcus mutans. Spleen plays roles in the clearance of circulating bacteria and antibody production; therefore, we hypothesized spleen may produce autoantibodies induced by circulating bacteria. We found that anti-dsDNA antibodies could be induced within 5-7 days after intravenous infection in the mouse model. The anti-dsDNA IgG levels were decreased in the mice with splenectomy, suggesting spleen can produce autoantibodies induced by circulating bacteria. The purified anti-dsDNA antibodies can cross-react with a S. mutans surface protein, glucosyltransferase B. On the other hand, systemic lupus erythematosus patients usually have high levels of anti-dsDNA antibodies. We found that a ribosomal protein named L7/L12 may not be an inducer of anti-dsDNA antibodies in SLE patients. Taken together, spleen play roles in autoantibody production caused by circulating infection, and the GtfB and L7/L12 may induce the cross-reactive autoantibody production.en
dc.description.provenanceMade available in DSpace on 2021-05-19T17:57:31Z (GMT). No. of bitstreams: 1
ntu-105-R03445118-1.pdf: 1432684 bytes, checksum: cccafc26ef6e39174eeb4637cb54ad48 (MD5)
Previous issue date: 2016
en
dc.description.tableofcontents口試委員審定書 I
致謝 II
Abstract II
中文摘要 III
Chapter 1. Introduction 1
1.1 The relationship between infection and autoantibody production 1
1.2 Systemic lupus erythematosus (SLE) 1
1.3 Streptococcus mutans 3
1.4 Glucosyltransferases 3
1.5 Glucan-binding protein B (GbpB)/60-kDa immunodominant glycoprotein (IdG60) 4
1.6 Spleen 5
1.7 Marginal zone B cells 6
Chapter 2.Purpose and Specific Aim 8
Chapter 3. Materials and methods 9
3.1 Animals 9
3.2 Bacterial strains and growth conditions 9
3.3 Streptococcal cell-wall-associated (CA) proteins extraction 10
3.4 Transform and purification of rIdG-60 11
3.5 Enzyme-linked immunosorbent assay (ELISA) 12
3.6 Antibody elution from ELISA plate wells 13
3.7 Western blotting (WB) 14
3.8 The preparation of splenocytes 14
3.9 Cell sorting and in vitro stimulation 15
3.10 Statistical analysis 15
Chapter 4. Results 16
4.1 Antibody production in mice intravenously or intraperitioneally infected with S. mutans 16
4.2 The reactivity of eluted anti-dsDNA antibodies to S. mutans proteins 16
4.3 The anti-dsDNA antibody production in the mice infected with S. aureus 17
4.4 The anti-dsDNA antibody production in the mice infected with S. mutans, NHR1DD or NHS1DD 18
4.5 Spleen may play roles in anti-bacterial and anti-dsDNA antibody production in mouse model 18
4.6 The antibody production in the normal and splenectomized mice 19
4.7 The stimulation of MZ B and FO B cells by using streptococcal proteins 19
4.8 The role of the bacterial ribosomal protein, L7/L12, in SLE 20
4.9 The correlation of anti-dsDNA antibodies and anti-bacterial antibodies in SLE patients 21
Chapter 5. Discussion 23
5.1 Intravascular bacterial infection may be important for the autoantibody production in autoimmune disease 23
5.2 The role of neutrophil extracellular traps (NETs) in autoantibody production 24
5.3 The cross-reactivity of GtfB and anti-dsDNA antibodies 25
5.4 The origin of anti-dsDNA antibodies 26
5.5 The role of L7/L12 in SLE patients 27
Chapter 6. References 29
Chapter 7. Table 37
Chapter 8. Figures 38
Table. Autoantibody production in patients with infective endocarditis and other disseminated systemic infections 37
Figure 1. Antibody production in mice intravenously or intraperitioneally infected with S. mutans 38
Figure 2. The reactivity of eluted anti-dsDNA antibodies to S. mutans proteins 40
Figure 3. The anti-dsDNA antibody production in the mice infected with S. aureus 42
Figure 4. The anti-dsDNA antibody production in the mice infected with S. mutans, NHR1DD or NHS1DD 43
Figure 5. Spleen may play roles in anti-bacterial and anti-dsDNA antibody production in mouse model 44
Figure 6. The antibody production in the normal and splenectomized mice 46
Figure 7. The stimulation of MZ B and FO B cells by using streptococcal proteins 48
Figure 8. The role of the bacterial ribosomal protein, L7/L12, in SLE 49
Figure 9. The role of the bacterial ribosomal protein, L7/L12, in SLE 51
Figure 10. The correlation of anti-dsDNA antibodies and anti-bacterial antibodies in SLE patients 53
dc.language.isoen
dc.title探討血液循環系統中的細菌感染引發自體抗體生成之機制zh_TW
dc.titleThe Mechanism of Autoantibody Production Caused by Circulating Bacteriaen
dc.typeThesis
dc.date.schoolyear104-2
dc.description.degree碩士
dc.contributor.oralexamcommittee李建國(Chien-Kuo Lee),林國儀(Kuo-I Lin),鍾筱菁(Chiau-Jing Jung)
dc.subject.keyword自體抗體,交叉反應,葡?基轉移?B,脾臟,zh_TW
dc.subject.keywordAutoantibodies,cross reaction,glucosyltransferase B,spleen,en
dc.relation.page53
dc.identifier.doi10.6342/NTU201602359
dc.rights.note同意授權(全球公開)
dc.date.accepted2016-08-15
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept微生物學研究所zh_TW
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