Guest guest Posted December 28, 2009 Report Share Posted December 28, 2009 this last part is very interesting. These findings suggest that a primary " danger signal " (Matzinger, 2002) might reprogram a host's innate immune system and render it sensitive to secondary signals by a toxicant. We hypothesized that macrophages might be critical targets for reprogramming of the innate immune system to a toxicant-sensitive state. The goal of this research was to test this hypothesis by determining (1) if LPS priming via TLR4 in vitro can sensitize macrophages to DON-induced proinflammatory gene expression, (2) whether other TLR agonists are capable of priming the macrophage response to DON, and (3) whether LPS priming of macrophages enhances their responsiveness to other toxicants known to induce proinflammatory gene expression. The results suggest that priming of macrophages via multiple TLRs increases their sensitivity to induction of inflammatory gene expression by DON and that, in an analogous fashion, LPS priming via TLR4 increases sensitivity to other toxicants with diverse mechanisms of action. sounds like a chemical sensitivity reaction minus the brain effects from passage through the BBB or up the nose to the brain. interesting, immune system might reprogram itself to render it sensitive to " a toxicant " that would mean any toxicant, not a sub-set of a certain toxicant, not one certain toxicant but any toxicant capable of warning the body of danger. this would bring up the fact that dose is very, very, important. > > Toll-Like Receptor Priming Sensitizes Macrophages to Proinflammatory Cytokine Gene Induction by Deoxynivalenol and Other Toxicants > full text 2006/cited > http://toxsci.oxfordjournals.org/cgi/content/full/92/2/445 > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted December 31, 2009 Report Share Posted December 31, 2009 well, at the risk of getting yelled at I'm just going to throw this out here. keep in mind that I am in no way a immuologest, just did alot of research on the immune system after I got somewhat of a understanding on anatomy. could have been my brain disfunctions but there just seemed to be a lot of things regarding the immune system that just didn't jive and oh so many different views, jikes. anyway, when I came across this, I just felt somethings started makeing more sence to me. makes me thing about Dr.Phil saying " and hows that working for you " a different view of how the immune system might function. purhapes PRRs have not evolved to bind to pathogens at all. perhaps the pathogens have evolved to bind to them for their own benifit. THE DANGER MODEL:RENEWED SENCE OF SELF/Polly Matzinger http://www.direct-ms.org/pdf/ImmunologyGeneral/DangerModel.pdf Polly Matzinger http://cmmg.biosci.wayne.edu/asg/polly.html http://users.telenet.be/nmertens/U11/IM2_immunology.htm immunology,danger signal Heat shock proteins form part of a danger signal cascade in response to lipopolysaccharide and GroEL. Collect - Hide Abstract + View Abstract An increasing number of cell types, including peripheral blood mononuclear cells (PBMCs), have been demonstrated to release heat shock proteins (Hsps). In this paper we investigate further the hypothesis that Hsps are danger signals. PBMCs and Jurkat cells released Hsp70 (0.22 and 0.7 ng/10(6) cells, respectively) into medium over 24 h at 37 degrees C. Release of Hsp70 was stimulated 10-fold by GroEL (P < 0.001) and more than threefold by lipopolysaccharide (LPS) (P < 0.001). Although Hsp60 could be detected in the medium of cells cultured at 37 degrees C for 24 h, the low rates of release were due probably to cell damage. Significant release of Hsp60 was observed when Jurkat cells were exposed to GroEL (2.88 ng/10(6) cells) or LPS (1.40 ng/10(6) cells). The data are consistent with the hypothesis that Hsp70 and Hsp60 are part of a danger signalling cascade in response to bacterial infection. Davies EL, Bacelar MM, Marshall MJ, E, Wardle TD, SM, and JH Clinical and experimental immunology 145(1):183, 2006 Jul - Who cited this? | PubMed ID: 16792689 | Fulltext http://www.labmeeting.com/paper/558479/davies-2006-heat-shock-proteins-form-part\ -of-a-danger-signal-cascade-in-response-to-lipopolysaccharide-and-groel Sensing danger--Hsp72 and HMGB1 as candidate signals. - cite this + cite this Collect - Hide Abstract + View Abstract Molecules that behave as danger signals are produced when the body is perceived to be under attack, and they alert the immune system to the problem. The immune system can then mount an appropriate response. Two molecules that have received attention as potential danger signals are heat shock protein 72 (Hsp72) and high mobility group box 1 (HMGB1), which are intracellular proteins but are released when cells are under stress, in particular, when necrosis occurs. This review considers the similarities between these two molecules and then contrasts their mechanism of action and problems that can arise when they are overpresented in the extracellular environment. It is proposed that Hsp72 and HMGB1 are members of a suite of danger molecules that provide a fingerprint of the threat, or stressor, to tissue or organism integrity. JH and Ireland HE Journal of leukocyte biology 83(3):489-92, 2008 Mar - Who cited this? | PubMed ID: 18156188 | Fulltext Hsp70 release from peripheral blood mononuclear cells. - cite this + cite this Collect - Hide Abstract + View Abstract There are an increasing number of studies reporting the presence of Hsps in human serum. We have investigated the release of Hsp70 into blood and culture medium from peripheral blood mononuclear cells (PBMCs), and whether this release is due to cell damage or active secretion from the cells. Intact Hsp70 was released from cells within whole blood and from purified PBMCs under normal culture conditions. Hsp70 release was rapid (0.1 ng/10(6) cells/h) over the first 2 h of culture and continued at a reduced rate up to 24 h (<0.025 ng/10(6) cells/h). Using viable cell counts and lactate dehydrogenase release we were able to confirm that the release of Hsp70 was not due to cellular damage. Hsp70 release was inhibited by monensin, methyl-beta-cyclodextrin, and methylamine, but not by brefeldin A. These data suggest that Hsp70 is released from cells via a non-classical pathway, possibly involving lysosomal lipid rafts. Hunter-Lavin C, Davies EL, Bacelar MM, Marshall MJ, SM, and JH Biochemical and biophysical research communications 324(2):511-7, 2004 Nov 12 - Who cited this? | PubMed ID: 15474457 | Fulltext ------------------ > > > > Toll-Like Receptor Priming Sensitizes Macrophages to Proinflammatory Cytokine Gene Induction by Deoxynivalenol and Other Toxicants > > full text 2006/cited > > http://toxsci.oxfordjournals.org/cgi/content/full/92/2/445 > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted December 31, 2009 Report Share Posted December 31, 2009 one reason this just nailed it for me was because I spent a hudge amount of time researching apoptosis vs. necrosis and over and over again necrosis, even through all the disputes, stood out as what was happening as a result of something toxic affecting our bodies, a unnatural cell death. it about drove me nuts,lol's, I had to put it aside but I was convienced that necrosis not apoptosis was a result of toxin exposure. but thats not the only reason,it just all makes sence to me, and haveing spent that much time reading about the immune system, and to read this paper and suddenly it's all clicks like that, I just loved it. > > well, at the risk of getting yelled at I'm just going to throw this out here. keep in mind that I am in no way a immuologest, just did alot of research on the immune system after I got somewhat of a understanding on anatomy. could have been my brain disfunctions but there just seemed to be a lot of things regarding the immune system that just didn't jive and oh so many different views, jikes. > anyway, when I came across this, I just felt somethings started makeing more sence to me. > makes me thing about Dr.Phil saying " and hows that working for you " > > a different view of how the immune system might function. > > purhapes PRRs have not evolved to bind to pathogens at all. > perhaps the pathogens have evolved to bind to them for their own benifit. > > THE DANGER MODEL:RENEWED SENCE OF SELF/Polly Matzinger > http://www.direct-ms.org/pdf/ImmunologyGeneral/DangerModel.pdf > > Polly Matzinger > http://cmmg.biosci.wayne.edu/asg/polly.html > http://users.telenet.be/nmertens/U11/IM2_immunology.htm > immunology,danger signal > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted December 31, 2009 Report Share Posted December 31, 2009 and no, I'm not saying apoptosis is not also accuring. just that it may be accuring for other reasons. > > one reason this just nailed it for me was because I spent a hudge amount of time researching apoptosis vs. necrosis and over and over again necrosis, even through all the disputes, stood out as what was happening as a result of something toxic affecting our bodies, a unnatural cell death. it about drove me nuts,lol's, I had to put it aside but I was convienced that necrosis not apoptosis was a result of toxin exposure. > but thats not the only reason,it just all makes sence to me, and haveing spent that much time reading about the immune system, and to read this paper and suddenly it's all clicks like that, I just loved it. Quote Link to comment Share on other sites More sharing options...
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