http://www.nature.com/nm/journal/v17/n8/full/nm.2403.html
DNA released from dying host cells mediates aluminum adjuvant activity
Thomas Marichal, Keiichi Ohata, Denis Bedoret, Claire Mesnil, Catherine
Sabatel, Kouji Kobiyama, Pierre Lekeux, Cevayir Coban, Shizuo Akira, Ken J
Ishii, Fabrice Bureau & Christophe J Desmet
Nature Medicine 17, 996–1002 (2011) doi:10.1038/nm.2403
Received 11 February 2011 Accepted 19 May 2011 Published online 17 July 2011
Abstract
Aluminum-based adjuvants (aluminum salts or alum) are widely used in human
vaccination, although their mechanisms of action are poorly understood. Here
we report that, in mice, alum causes cell death and the subsequent release of
host cell DNA, which acts as a potent endogenous immunostimulatory signal
mediating alum adjuvant activity. Furthermore, we propose that host DNA
signaling differentially regulates IgE and IgG1 production after
alum-adjuvanted immunization. We suggest that, on the one hand, host DNA
induces primary B cell responses, including IgG1 production, through
interferon response factor 3 (Irf3)-independent mechanisms. On the other
hand, we suggest that host DNA also stimulates 'canonical' T helper type 2
(TH2) responses, associated with IgE isotype switching and peripheral
effector responses, through Irf3-dependent mechanisms. The finding that host
DNA released from dying cells acts as a damage-associated molecular pattern
that mediates alum adjuvant activity may increase our understanding of the
mechanisms of action of current vaccines and help in the design of new
adjuvants.
簡單來說
Alum常用來做為疫苗的佐劑(Adjuvant)，促使疫苗增加其免疫效應
而Alum已經使用了幾十年而且效果顯著，但是卻沒有人清楚其中原理機制
直到最近才有研究指出，Alum會破壞Host cell (通常是Dendritic Cell)
而使Host cell釋放出DNA片段
而這些DNA片段會去刺激免疫系統促使其增加活化免疫反應
最終提高免疫細胞對疫苗的反應能力而達到免疫保護效果
可是alum提高免疫反應除了製造出IgG1, 也會刺激致造出IgE
然而IgE的提高會造成自體免疫反應，也就是俗稱的過敏反應
日本的大阪大學研究人員發現
支那飄來的PM2.5懸浮微粒裡面包含了大量的Alum結構
人一旦暴露在裡面等於刺激了免疫反應升級
在日本有大量的花粉症，尤其是在霧霾最嚴重的那幾天之後會大量增加花粉症患者
推測是因為Alum刺激了免疫反應之後，少許花粉吸入就會造成過敏反應
在霧霾飄來加上花粉大量漂散的時期，將會造成相當多人的困擾
這也就是為什麼PM2.5肆虐的時候
台灣也增加很多過敏患者(眼睛癢 流眼淚 打噴嚏流鼻涕 皮膚發癢)
八卦在於
alum背後的機制一直沒什麼人想研究，因為已經發展幾十年了只知道這東西很有用
後來日本大阪大學的Ken J. Ishii却很堅持一直鑽研下去
http://www.ifrec.osaka-u.ac.jp/en/laboratory/vaccinescience/
某一天他的學生發現加入alum的Dendritic Cell死掉了而導致DNA片段釋出
他們在顯微鏡上看到DAPI染色的DNA跑到細胞外
當時他還覺得根本是學生做錯了或看錯了或汙染了細胞
後來重複了好幾次加上其他實驗佐證才驚覺這是真的
因此發現了Alum背後的作用機制以及未來可能利用DNA片段或其他相似化合物來做為佐劑