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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 分子醫學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41614
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor余家利(Chia-Li Yu)
dc.contributor.authorShih-Yin Huangen
dc.contributor.author黃詩穎zh_TW
dc.date.accessioned2021-06-15T00:24:52Z-
dc.date.available2010-02-17
dc.date.copyright2009-02-17
dc.date.issued2009
dc.date.submitted2009-01-23
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18. Eric Vivier, Elena Tomasello, Pascale Paul: Lymphocyte activation via NKG2D: towards a new paradigm in immune recognition? Curr Opin Immunol. 14(3): 306-311, 2002.
19. Helmut R. Salih, Hans-Georg Rammensee, Alexander Steinle: Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J. immunol. 169(8): 4098–4102, 2002.
20. Ekaterina S. Doubrovina, Mikhail M. Doubrovina, Elena Vider, Richard B. Sissorn, Richard J. O’Reilly, Bo Dupont, Yatin M. Vyas. Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J. immunol. 171(12): 6891–6899, 2003.
21. Veronika Groh, Jennifer Wu, Cassian Yee, Thomas Spies: Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 419(6908): 734-738, 2002.
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23. A.G. Moore, D.A. Brown, W.D Fairlie, A.R. Bauskin, P.K, Brown, M.L.C. Munier, P.K. Russell, L.A. Salamonsen, E.M. Wallace, S.N. Breit: The Transforming Growth Factor-b Superfamily Cytokine Macrophage Inhibitory Cytokine-1 Is Present in High Concentrations in the Serum of Pregnant Women. J Clini Endocrino Metaboli. 85(12): 4781-4788, 2008.
24. Felice Petraglia, Shaily Garg, Pasquale Florio, Mike Sadick, Andrea GalIinelIi, Wai-Lee Wong, Lynne Krummen, Giuseppina Comitini, Jennie Mather, Teresa K. Woodruff: Activin A and activin B measured in maternal serum, cord blood serum and amniotic fluid during human pregnancy. Endocr J. 1: 323-327, 1993
25. Rinat Hackmon, Arie Koifman, Hirohito Hyobo, Hagit Glickman, Eyal Sheiner, Daniel E. Geraghty: Reduced third-trimester levels of soluble human leukocyte antigen G protein in severe preeclampsia. Am J Obstet Gynecol. 197:255e1-255e5, 2007.
26. Jose Carlos Peracoli, Marilza Vieira Cunha Rudge, Maria Terezinha Serrao Peracoli: Tumor Necrosis Factor-alpha in Gestation and Puerperium of Women with Gestational Hypertension and Pre-eclampsia. Am J Reprod Immunol. 57:177-185, 2007.
27. Aliz Barakonyi, Polgar B, Julia Szekeres-Bartho: The role of gamma/delta T-cell receptor-positive cells in pregnancy: part II. Am J Reprod Immunol. 42:83–87, 1999.
28. Aliz Barakonyi, Eva Miko, Peter Varga, Julia Szekeres-Bartho: V-Chain Preference of Gamma/Delta T-Cell Receptors in Peripheral Blood During Term Labor. Am J Reprod Immunol. 59(3): 201-205, 2008
29. Neil Hamill, Roberto Romero, Francesca Gotsch, Juan Pedro Kusanovic, Sam Edwin, Offer Erez, Shali Mazaki-Tovi, Sonia Hassan: Exodus-1(CCL20): evidence for the participation of this chemokine in spontaneous labor at term, preterm labor, and intrauterine infection. J Perina medic. 36(3): 217-227, 2008
30. Roberto Romero, Jimmy Espinoza, Sonia Hassan, Francesca Gotsch, Juan Pedro Kusanovic, Cecilia Avila, Offer Erez, Sam Edwin, Ann Marie Schmidt: Soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) in amniotic fluid: modulation by infection and inflammation. J Perina Medic. 36(5):388-398, 2008.
31. Pooja Mittal, Roberto Romero, Juan Pedro Kusanovic, Samuel S Edwin, Francesca Gotsch, Shali Mazaki-Tovi, Jimmy Espinoza, Offer Erez, Nhan Chang, Chia Ling, Nandor G Than, Edi Vaisbuch, Sonia S Hassan: CXCL6 (Granulocyte Chemotactic Protein-2): A Novel Chemokine Involved in the Innate Immune Response of the Amniotic Cavity. Am J Reprod Immunol. 60(3):246-257, 2008
32. Shari E. Gelber, Shari E., Ann Marie Bongiovanni, Claudel Jean-Pierre, Iara M.Linhares, Daniel W. Skupski, Steven S.Witkin: Antibodies to the 70 kDa heat shock protein in midtrimester amniotic fluid and intraamniotic immunity. Am J Obstet Gynecol. 197(3):278e1-278e4., 2007
33. Riikka Aaltonen, Tuija Heikkinen, Kristo MSc Hakala, Kari Laine, Anna Alanen: Transfer of Proinflammatory Cytokines Across Term Placenta. Obstet Gynecol. 106(4):802-807, 2005.
34. Wegmann TG, Lin H, GuilbertL, Mosmann TR. Bi-directional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a Th2 phenomenon? Immunol Today. 14:353–356, 1993.
35. Chaouat G, Meliani AA, Martal G, Radhupathy R, ElliotG, Mosmann TR, Wegmann TG. IL-10 prevents naturally occurring fetal loss in the CBAxDBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vitro injection of IFN-τ. J Immunol. 154:4261–4270, 1995.
36. Raghupathy R. Th-1 type immunity is incompatible with successful pregnancy. Immunol Today. 18:478–482, 1997.
37. Hagai Amsalem, Anat Gaiger, Sa'ar Mizrahi, Simcha Yagel, Jacob Rachmilewitz: Characterization of a lymphocyte subset displaying a unique regulatory activity in human decidua. Internat Immunol. 20:1147-1154, 2008.
38. Olga Nagaeva, Lena Jonsson, Lucia Mincheva-Nilsson: Dominant IL-10 and TGF-β mRNA expression in γδT cells of human early pregnancy deciduas suggests immunoregulatory potential. Am J Reprod Immunol. 48: 9-17, 2002.
39. Yoon Kyong Choi, Joanne Kwak-Kim: Cytokine Gene Polymorphisms in Recurrent Spontaneous Abortions: A Comprehensive Review. Am J Reprod Immunol. 60: 91–110, 2008.
40. Fukui A, Kwak-Kim J, Ntrivalas E, Gilman-Sachs A, Lee SK, Beaman K: Intracellular cytokine expression of peripheral blood natural killer cell subsets in women with recurrent spontaneous abortions and implantation failures. Fertil Steril. 89:157–165, 2008.
41. Saito S.: Cytokine network at the feto–maternal interface. J Reprod Immunol 47:87–103, 2000.
42. Torn, Carina. Gupta, Manu. Sanjeevi, Carani B. Aberg, Anders. Frid, Anders. Landin-Olsson, Mona.: Different HLA-DR-DQ and MHC class I chain-related gene A (MICA) genotypes in autoimmune and nonautoimmune gestational diabetes in a Swedish population. Hum Immunol. 65(12):1443-1450, 2004
43. Porcu-Buisson, Geraldine. Lambert, Marion. Lyonnet, Luc. Loundou, Anderson. Gamerre, Marc. Camoin-Jau, Laurence. Dignat-George, Francoise. Caillat-Zucman, Sophie. Paul, Pascale: Soluble MHC Class I chain-related molecule serum levels are predictive markers of implantation failure and successful term pregnancies following IVF. Hum Reprod. 22:2261-2266, 2007.
44. G L.Veith, G E. Rice. Interferon gamma expression during human pregnancy and in association with labor. Gynecol Obstet Invest. 48(3):163-167, 1999.
45. Jones, C A. Finlay-Jones, J J. Hart, P H. Type-1 and type-2 cytokines in human late-gestation decidual tissue. Biolog Reprod. 57:303-311, 1997.
46. Olah, K S. Vince, G S. Neilson, J P. Deniz, G. Johnson, P M. Interleukin-6, interferon-gamma, interleukin-8, and granulocyte-macrophage colony stimulating factor levels in human amniotic fluid at term. J Reprod Immunol. 32(1):89-98, 1996.
47. Zivile Cerkiene, Audrone Eidukaite, Audrone Usoniene: Follicular Fluid Levels of Interleukin-10 and Interferon-gamma do not Predict Outcome of Assisted Reproductive Technologies. Am J Reprod Immunol. 59(2): 118–126, 2008.
48. Bianca Schaub, Jing Liu, Sabine Hoppler, Severine Haug, Christine Sattler, Anna Lluis, Sabina Illi, Erika von Mutius: Impairment of T-regulatory cells in cord blood of atopic mothers. J Allerg Clini Immunol. 121(6):1491-1499, 2008.
49. Shobokshi, A. Shaarawy, M. Maternal serum and amniotic fluid cytokines in patients with preterm premature rupture of membranes with and without intrauterine infection. Internat J Gynaecol Obstet. 79(3):209-215, 2002.
50. Negishi, H. Yamada, H. Mikuni, M. Kishida, T. Okuyama, K. Sagawa, T. Makinoda, S. Fujimoto, S. Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery. J Perinat Medic. 24(6):633-639, 1996.
51. Malamitsi-Puchner, Ariadne. Vrachnis, Nikolaos. Samoli, Evi. Baka, Stavroula. Iliodromiti, Zoe. Puchner, Karl-Philipp. Malligianis, Pantelis. Hassiakos, Dimitrios. Possible early prediction of preterm birth by determination of novel proinflammatory factors in midtrimester amniotic fluid. Ann N Y Aca Sci. 1092:440-449, 2006.
52. Malamitsi-Puchner, Ariadne. Vrachnis, Nikolaos. Samoli, Evi. Baka, Stavroula. Hassiakos, Demetrios. Creatsas, George. Elevated second trimester amniotic fluid interferon gamma-inducible T-cell alpha chemoattractant concentrations as a possible predictor of preterm birth. J Socie Gynecol Investig. 13(1):25-29, 2006.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41614-
dc.description.abstract胎兒對母體而言是一種半同種異體移植物,在懷孕過程中不會遭受到母體的排斥是一種很特別的免疫現象。有許多免疫學上的假說,針對這個現象提出各種免疫逃脫機制的理論。Lucia Mincheva-Nilsson et al.在2006年提出一個新的胎兒對母體免疫反應的逃脫機制:人類的胎盤會分泌可溶性的MICA/B,它會與母體自然殺手細胞上的NKG2D受體結合,進而調節降低細胞的毒殺活性。根據這項研究推測:正常懷孕的婦女,隨著妊娠的進展及胎兒的成長,為保護胎兒不受母體的免疫細胞攻擊,母體血液中的可溶性MICA/B值應該會隨著妊娠週數增加。因此,本次研究收集了290位懷孕婦女的血清,分前、中、及後三個妊娠期,抽取母體周邊血液共337管,以ELISA分析可溶性MICA/B在正常妊娠期的變化。結果顯示:可溶性MICA/B在懷孕初期會隨著妊娠進展而增加,在孕程中期達到最高,但在接近生產時會下降,甚至低於孕程前期。針對此項發現我們進一步提出假設:在接近生產時,因胎盤功能的老化,使得胎盤分泌可溶性的MICA/B的能力降低所致,因此母體內可偵測到的可溶性MICA/B也相對下降。同時我們推論這可能也是誘發產程的機轉之一。另外,本次研究收集35位懷孕中期婦女的羊水,偵測其羊水中MICA/B的濃度及羊水對單核球產生IFN-γ及IL-10的影響。研究結果顯示:羊水內MICA/B的含量極低,但是我們發現有些羊水會抑制活化單核球產生IFN-γ,但不影響IL-10的產生。因此我們推論MICA/B與NKG2D的反應只局限於母體與胎盤間,並未穿過胎盤到達羊膜腔內,而羊水含有某些會抑制細胞性免疫功能的分子,其特性正在探討中zh_TW
dc.description.abstractThe survival of the semi-allogeneic fetus which can escape from the maternal immune attack during human normal pregnancy is a special immunological phenomenon. Several hypothetical mechanisms are proposed to explain these particular modifications of the immune status of the mother. Lucia Mincheva-Nilsson et al. (2006) suggested a new physiological mechanism for fetal evasion from maternal immune attack in that the engagement and down-regulation of the NK cell receptor NKG2D by soluble MHC class I chain-related proteins (sMIC) A and B derived from placenta occurred in the mother side. Following this report, we hypothesized that the sMICA/B level would increase in proportion to the gestational age for protecting the fetus from maternal immune rejection in the normal pregnancy. In the present study, we collected 337 serum specimens from 290 normal pregnancy women for sMICA/B analysis. We found the serum sMICA/B level rose gradually with the progression of gestation, and reached the peak value in the second trimester. The sMICA/B level decreased after the third trimester, with the lowest level appearing before delivery. According to these findings, we conclude that when approaching delivery, the aged placenta produces reduced amount of soluble MICA/B and induce the labor.
In addition, we collected 10 amniotic fluid samples from the normal second-trimester pregnant women and measured the concentration of soluble MICA/B in amniotic fluid. We found the level of soluble MICA/B were extremely low in amniotic fluid. We suggest the effect of soluble MICA/B on natural killer cells of the pregnant women is limited to the placental maternal surface, but not transferring through the placenta into the amniotic cavity. In addition, we collected another 25 amniotic fluid samples from the normal second-trimester pregnant women and analyzed the influence of amniotic fluid on the TH1/TH2 cytokine production of the activated mononuclear cell. Interestingly, we demonstrated that some of the amniotic fluid suppressed IFN-γ, but not IL-10, production by anti-CD3+/anti-CD28 activated mononuclear cells. In conclusion, both pregnancy serum and amniotic fluid exhibit immno-modulatory effects on the feto-maternal inmmunotolerance.
en
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Previous issue date: 2009
en
dc.description.tableofcontents口試委員會審定書 I
致謝 II
摘要 III
Abstract IV
1. Introduction 01
1.1. Human pregnancy 01
1.2. Feto-maternal immunotolerance 02
1.3. MHC Class I chain-Related Molecules 03
1.4. NKG2D receptor on NK cells 04
1.5. Soluble MICA/B vs. NKG2D 04
1.6. Novel immune escape mechanism for fetal survival 05
1.7. Specific aim of the present study 05
2. Materials and Methods 06
2.1. Samples collection and preparation 06
2.2. Antibodies and reagents 07
2.3. Capture Enzyme-linked immunosorbent assays (ELISA) for sMICA/B 07
2.4. Isolation of mononuclear cells from normal human peripheral blood 08
2.5. Preparation of culture supernatants 09
2.6. ELISA for TH1/TH2 cytokines in the culture supernatants 09
2.7. Statistical assessment 10
3. Result 11
3.1. Samples analysis 11
3.2. The concentration of soluble MICA/B during pregnancy 12
3.3. The concentration of soluble MICA/B in amniotic fluid 13
3.4. The expression of TH1/TH2 cytokines of PBMC after co-culture with amniotic fluid 13
3.5. Different protein profile in IFN-γ suppressive and non-suppressive amniotic fluids 14
4. Discussion 15
4.1. Increase production of sMICA/B during pregnancy 16
4.2. The biological significance of decreasing sMICA/B before delivery 17
4.3. The absence of sMICA/B in amniotic fluid 18
4.4. The influence of amniotic fluid to mononuclear cell production of TH1/TH2 Cytokine 19
5. Conclusion 22
6. Future study 23
7. Reference 25
8. Table 35
Table 1: The serum concentration of sMICA/B progressively increased in proportion
to the gestational age before 30th week 35
Table 2: The serum concentration of sMICA/B decreased in proportion to
gestational age after 28th week (mid-trimester) 36
Table 3: The serial changes of serum sMICA/B from early pregnancy to delivery 37
9. Figure and Figure Legends 38
Figure 1: The alterations of serum sMICA/B concentration during pregnancy 38
Figure 2: The serum concentration of sMICA/B in first and second trimester 39
Figure 3: The serum concentration of sMICA/B before delivery 40
Figure 4: The concentration of sMICA/B in amniotic fluid 41
Figure 5: The effect of amniotic fluid on mononuclear cell TH2 cytokine IL-10
Production………………………………………………………………..42
Figure 6: The effect of amniotic fluid on mononuclear cell TH1 cytokine IFN-
dc.language.isoen
dc.subject懷孕zh_TW
dc.subject可溶性MICA/Bzh_TW
dc.subjectIFN-γzh_TW
dc.subject免疫逃脫機制zh_TW
dc.subject羊水zh_TW
dc.subjectIFN-γen
dc.subjectsMICA/Ben
dc.subjectimmune evasionen
dc.subjectpregnancyen
dc.subjectamniotic fluiden
dc.title胎盤衍生的可溶性MICA/B在懷孕血清中的變化及羊水對活化的單核性細胞產生TH1/TH2細胞激素的影響zh_TW
dc.titleThe Alteration of Placental-Derived Soluble MHC Class I Chain-Related Protein A and B during Pregnancy and the Influence of Amniotic Fluid on Activated Mononuclear Cell TH1/TH2 Cytokine Productionen
dc.typeThesis
dc.date.schoolyear97-1
dc.description.degree碩士
dc.contributor.oralexamcommittee蔡長祐,謝松洲
dc.subject.keyword可溶性MICA/B,免疫逃脫機制,懷孕,羊水,IFN-γ,zh_TW
dc.subject.keywordsMICA/B,immune evasion,pregnancy,amniotic fluid,IFN-γ,en
dc.relation.page46
dc.rights.note有償授權
dc.date.accepted2009-01-23
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept分子醫學研究所zh_TW
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