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標題: | 以OVA致敏小鼠模式評估去活性流感病毒疫苗對過敏性氣喘之影響 Evaluation of Inactivated Influenza Vaccination on Allergic Asthma in an OVA-immunized Mouse Model |
作者: | You-Ru Jang 簡佑儒 |
指導教授: | 莊雅惠(Ya-Hui Chuang) |
關鍵字: | 氣喘,呼吸道發炎反應,肺臟沖洗液,流感病毒,流感疫苗, asthma,airway inflammation,broncho-alveolar lavage fluid (BALF),influenza virus,flu vaccine, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | 過敏性氣喘是人體對過敏原產生過度TH2反應的一種疾病。病人呼吸道有長期的慢性發炎,當吸入過敏原時會產生急性反應,如平滑肌收縮、黏液分泌等,稱為呼吸道過度反應,使呼吸道狹窄,病人因此不易吸入空氣而導致咳嗽、喘鳴等典型氣喘病徵。流感病毒是感染呼吸道上皮細胞的一種RNA病毒,每年會造成季節性流行,但可藉由施打疫苗以避免病毒感染。氣喘病人是感染流感病毒後引發重症的高危險群,然而,疫苗主要使人體產生抗病毒的TH1免疫反應,可能與氣喘病人的TH2免疫反應互相拮抗,但也可能使病人呼吸道發炎反應增強。目前仍沒有詳細研究流感疫苗產生的免疫反應會對氣喘病人造成何種影響,本研究探討去活性流感病毒疫苗對於OVA所引起之小鼠氣喘之影響。
研究結果顯示,流感病毒使用紫外光照射去活性後,打入小鼠體內可以使小鼠產生抗病毒抗體。接著將去活性流感病毒疫苗施打於OVA致敏之小鼠,在最後一次施打疫苗後兩天、五天以及七天給予OVA刺激,評估疫苗所引起之先天性及後天性免疫反應是否對氣喘小鼠造成影響。結果發現疫苗的施打並不影響呼吸道發炎反應,血清中OVA特異性IgE濃度沒有改變,肺臟沖洗液之發炎細胞的種類、數目以及細胞激素濃度亦沒有顯著的改變。然而,在施打疫苗後七天給予OVA 刺激的實驗中,施打較高劑量疫苗的氣喘小鼠,其肺泡沖洗液中的IL-4以及IL-6明顯低於不施打疫苗的控制組。 以上結果顯示,施打病毒後,即使小鼠產生強烈的抗病毒抗體反應,也不會使氣喘相關之免疫反應加劇,反而可能與TH2免疫反應拮抗,而抑制與氣喘相關之細胞激素的產生。因此,未來除了以流感病毒感染氣喘小鼠,探討疫苗在其體內的保護力,也可進一步探討疫苗與TH2免疫反應拮抗的相關機轉。 Asthma is a heterogeneous disorder characterized by airway inflammation and airway hyper-reactivity (AHR). The symptoms of asthma are recurrent wheezing, coughing and shortness of breath. Allergic asthma is the most common type of asthma. Allergen-specific TH2 cells, eosinophils, and the production of allergen-specific IgE are the cardinal features of allergic asthma. Influenza virus is a single strand segmented RNA virus mainly infected airway epithelial cells. Every year influenza virus can cause seasonal epidemics and results in many hospitalizations and deaths. Asthma patients are high risk group for serious disease from influenza infection. Fortunately, flu vaccine can effectively prevent influenza infection, so many countries recommend asthma patients to receive flu vaccination. However, whether influenza vaccine is safe for asthma patients is still unclear. The aim of this study is to evaluate the safety and impact of influenza vaccine on allergic asthma in an OVA-immunized mouse model. To investigate the impact of different vaccine-induced immune response, innate and adaptive immunity, OVA-sensitized mice were challenged at different time points after vaccination. The results showed that intramuscular vaccination induces strong anti-virus immune response but not inflammatory response in asthma mice of all groups. Furthermore, the characteristics of asthma such as OVA specific IgE, cytokines, cell numbers and population in broncho-alveolar lavage fluid (BALF) were not increased after vaccination. Moreover, we found that some of these phenotypes, IL-4 and IL-6, were significantly decreased. Our data demonstrated that vaccination doesn’t exacerbate asthmatic phenotypes in mice. In contrast, TH1 biased vaccine response may somehow suppress TH2 immune response in asthma. In the future, the protective effect of flu vaccine in asthma mouse and the relationship between different immune responses induced by vaccine and asthma, respectively, will be investigated. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/34340 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
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