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.
简单来说
Alum常用来做为疫苗的佐剂(Adjuvant)，促使疫苗增加其免疫效应
而Alum已经使用了几十年而且效果显著，但是却没有人清楚其中原理机制
直到最近才有研究指出，Alum会破坏Host cell (通常是Dendritic Cell)
而使Host cell释放出DNA片段
而这些DNA片段会去刺激免疫系统促使其增加活化免疫反应
最终提高免疫细胞对疫苗的反应能力而达到免疫保护效果
可是alum提高免疫反应除了制造出IgG1, 也会刺激致造出IgE
然而IgE的提高会造成自体免疫反应，也就是俗称的过敏反应
日本的大阪大学研究人员发现
支那飘来的PM2.5悬浮微粒里面包含了大量的Alum结构
人一旦暴露在里面等于刺激了免疫反应升级
在日本有大量的花粉症，尤其是在雾霾最严重的那几天之后会大量增加花粉症患者
推测是因为Alum刺激了免疫反应之后，少许花粉吸入就会造成过敏反应
在雾霾飘来加上花粉大量漂散的时期，将会造成相当多人的困扰
这也就是为什么PM2.5肆虐的时候
台湾也增加很多过敏患者(眼睛痒 流眼泪 打喷嚏流鼻涕 皮肤发痒)
八卦在于
alum背后的机制一直没什么人想研究，因为已经发展几十年了只知道这东西很有用
后来日本大阪大学的Ken J. Ishii却很坚持一直钻研下去
http://www.ifrec.osaka-u.ac.jp/en/laboratory/vaccinescience/
某一天他的学生发现加入alum的Dendritic Cell死掉了而导致DNA片段释出
他们在显微镜上看到DAPI染色的DNA跑到细胞外
当时他还觉得根本是学生做错了或看错了或污染了细胞
后来重复了好几次加上其他实验佐证才惊觉这是真的
因此发现了Alum背后的作用机制以及未来可能利用DNA片段或其他相似化合物来做为佐剂