出版年:

研究生:

劉怡霞

研究生(英文姓名):

Yi-Hsia Liu

論文名稱:

佐劑對由塵璊在小鼠引發肺臟發炎反應之影響

英文論文名稱:

Influence of Adjuvants on Dust Mite Dermatophagoides farinae -Induced Pulmonary Inflammation in Sensitized Mice

指導教授:

余俊強

指導教授(英文姓名):

Chun-Keung Yu

學位類別:

碩士

校院名稱:

國立成功大學　

系所名稱:

微生物暨免疫學研究所

學號:

S46861084

學年度:

87

語文別:

中文

論文頁數:

80

關鍵詞:

塵璊 ; 過敏原 ; 嗜酸性球 ; 細胞激素

英文關鍵詞:

Der f ; allergens ; eosinophilis ; IgE ; cytokines

被引用次數:

0

[ 摘要 ]

在過敏性氣喘的慢性呼吸道嗜酸性球發炎反應的形成過程中，過敏原的長期暴露是一個重要因子。傳統上研究過敏性氣喘的動物模式，大都利用氫氧化鋁混合過敏原經單次激發而造成的過敏反應，包括肺部有嗜酸性球浸潤，和血清中過敏原特異性IgE抗體的產生。我們曾證實經家塵璊混合弗氏完全佐劑致敏的小鼠經呼吸道激發後同樣產生嗜酸性球發炎，然而並沒特異性IgE的參與。因此本實驗的目的就是（1）探討單次和多次塵璊激發後致敏小鼠後呼吸道發炎反應的差異，和（2）氫氧化鋁和弗氏完全佐劑誘發的氣喘動物模式中，經家塵璊氣管內激發後所表現出來的免疫反應的差異和可能造成的機制。
我們的結果發現氫氧化鋁致敏的小鼠在塵璊多次激發後出現一個嚴重的呼吸道嗜酸性球的發炎反應，同時伴隨血清中IgE抗體，Th2型細胞激素和嗜酸性球的增加。相反的經弗氏完全佐劑致敏的小鼠在塵璊激發後無論是肺部細胞總數、肺部嗜酸性球、血中嗜酸性球、IL-4、IL-5、總IgE和特異性IgE等量都較氫氧化鋁致敏小鼠為低；但是IFN-g 和特異性IgG抗體上則較氫氧化鋁致敏小鼠為高。在氫氧化鋁致敏小鼠的肺泡沖洗液中也較弗氏完全佐劑致敏小鼠有更多的CD4+ T細胞。此外細胞流體分析儀分析指出，在過敏原激發後，有一群從週邊進入肺臟的細胞，這群細胞在氫氧化鋁致敏的小鼠中表現較多的B7分子。而在被動給予弗氏完全佐劑致敏小鼠抗塵血清後發現，弗氏完全佐劑致敏小鼠在肺部的發炎反應並未受很大的影響。
綜合本實驗，我們發現氫氧化鋁致敏小鼠經塵璊過敏原多次激發後可以造成一個嚴重的呼吸道嗜酸性球發炎反應，而弗氏完全佐劑致敏小鼠則產生不具IgE抗體的呼吸道發炎反應。兩者差異的原因，可能與不同佐劑激發後不同細胞激素或不同的輔助刺激分子表現有關。

[ 英文摘要 ]

Parental immunization with allergens in the presence of adjuvants especially alum with subsequent single challenge is the most common protocol to induce experimental allergic airway inflammation in mice. These animals characteristically display eosinophila and allergen specific IgE antibody, the unique features of bronchial asthma. On the other hand, we have demonstrated that immunization of BALB/c mice with dust mite Dermatophagoides farinae (Der f) in the presence of complete Freund''s adjuvant (CFA) would induce pulmonary eosinophilia without allergen specific IgE production after challenge. Therefore in this study, we attempted to compare the effect of alum and CFA on the Der f-induced allergic airway responses after single or multiple challenge.
We demonstrated that alum-sensitized mice developed a severe pulmonary eosinophilic inflammation after multiple challenge as compared with single-challenge mice. In addition, the numbers of blood eosinophils and pulmonary CD4+ T cells, and the levels of Th2 type cytokines (IL-4 and IL-5) in blood and bronchoalveolar lavage (BAL) fluids of Der f/alum-sensitized mice were significantly higher than those of Der f/CFA-sensitized mice. On the contrary, Der f/CFA-sensitized mice had significantly higher levels of Der f-specific IgG and IFN-g than Der f/alum-sensitized mice. Flow cytometry analysis of BAL cells of sensitized mice revealed the appearance of a group of cells which had smaller size and contained less granules than the original BAL cells after challenge. Furthermore, the cells expressed the B7 molecules. Passive transfer of anti-Der f immune serum, either the IgE or IgG class, to CFA-sensitized mice did not alter the Der f-induced pulmonary inflammation.
We concluded that the substantial difference between the responses of the alum-sensitized and CFA-sensitized mice after Der f challenge were at least in part due to the type of cytokines elicited by individual adjuvant. Furthermore, these adjuvants might preferentially induce certain types of co-stimulatory molecules which are known to be important for the development of allergic responses.