Guest guest Posted September 5, 2010 Report Share Posted September 5, 2010 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 ----------------- Toll-Like Receptor Priming Sensitizes Macrophages to Proinflammatory Cytokine Gene Induction by Deoxynivalenol and Other Toxicants 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. http://toxsci.oxfordjournals.org/content/92/2/445.full ------------- this is a good read on mast cell functions http://www3.interscience.wiley.com/cgi-bin/fulltext/123563063/HTMLSTART Along with DC, mast cells are well positioned to be one of the first cells of the immune system to interact with environmental Ag, environmentally derived toxins, or invading pathogens But one thing is certain: evolution did not give us mast cells so that we can eat a peanut and die. Answering these questions will take time. It is already clear, however, that mast cells have a much larger spectrum of potential roles in health and disease than was thought only a short time ago, when interest focused mainly on their role as effector cells in IgE-associated responses. Indeed, mast cells are increasingly viewed as versatile effector and immunoregulatory cells that occupy a critical position at the interface of innate and acquired immunity, where, depending on circumstances that remain to be fully understood, mast cells may either help to sustain and restore health or contribute to disease. ------------------ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 5, 2010 Report Share Posted September 5, 2010 The Papers by Pestka, Laska and Kankkunen are the basis of what I have been attempting to tell everyone. Not only are the peripheral macrophages activated so are those of the central nervous system (microglia). It is interesting to note that the American Chemical Society permitted the publication of the Laska paper. There is a feedback between the peripheral innate immune system (macrophages) and the CNS innate immune system (Microglia). Thanks for posting these important papers. [] THE DANGER MODEL 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 ----------------- Toll-Like Receptor Priming Sensitizes Macrophages to Proinflammatory Cytokine Gene Induction by Deoxynivalenol and Other Toxicants 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. http://toxsci.oxfordjournals.org/content/92/2/445.full ------------- this is a good read on mast cell functions http://www3.interscience.wiley.com/cgi-bin/fulltext/123563063/HTMLSTART Along with DC, mast cells are well positioned to be one of the first cells of the immune system to interact with environmental Ag, environmentally derived toxins, or invading pathogens But one thing is certain: evolution did not give us mast cells so that we can eat a peanut and die. Answering these questions will take time. It is already clear, however, that mast cells have a much larger spectrum of potential roles in health and disease than was thought only a short time ago, when interest focused mainly on their role as effector cells in IgE-associated responses. Indeed, mast cells are increasingly viewed as versatile effector and immunoregulatory cells that occupy a critical position at the interface of innate and acquired immunity, where, depending on circumstances that remain to be fully understood, mast cells may either help to sustain and restore health or contribute to disease. ------------------ Quote Link to comment Share on other sites More sharing options...
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