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--- home:publications:proal_autoimmunity_2010 [06.15.2010] – marysue
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 ====#8 Nuclear receptors down regulated upon infection====
-Take, for example, the Vitamin D Receptor or VDR - a type 1 nuclear receptor. Well, it turns out that viruses like Epstein-Barr Virus and bacteria like //Mycobacterium tuberculosis// have evolved to survive in the same fashion - and that's by slowing activity of the VDR.(({{pubmed>long:19550398}})) For example, MTb downregulates VDR activity by about a factor of 3.3.  And, this slide shows VDR activity being downregulated actually, by almost a factor of 30 in the longer lasting cell lines of B cells infected with EBV.
+Take, for example, the Vitamin D Receptor or VDR - it's a type 1 nuclear receptor. Well, it turns out that viruses like Epstein-Barr Virus and bacteria like //Mycobacterium tuberculosis// have evolved to survive in the same fashion - and that's by slowing activity of the VDR.(({{pubmed>long:19550398}}))  For example, MTb downregulates VDR activity by about a factor of 3.3.  And, this slide shows VDR activity being downregulated actually, by almost a factor of 30 in the longer lasting cell lines of B cells infected with EBV.
 ====#9 The Vitamin D Receptor (VDR)====
-Why the VDR? Well, colloquially speaking, the VDR serves as a "gatekeeper" to the innate immune response - So, it expresses Cathelecidin, it expresses these key endogenous antimicrobials, that the body needs to actually target these intracellular pathogens. - Cathelecidin - the beta-Defensins - it also expresses Toll-like receptor 2. In addition to that, it expresses at least 913 genes, many connected to autoimmune diseases and cancers. So by dysregulating and slowing the VDR, Epstein-Barr Virus and Mycobacterium tuberculosis have actually evolved to slow the body's very defense mechanisms that would otherwise be actively working to render them dead.
+So, basically - you might ask, why the VDR? Well, colloquially speaking, the VDR serves as a "gatekeeper" to the innate immune response - So, it expresses Cathelecidin, it expresses these key endogenous antimicrobials, that the body needs in order to target intracellular pathogens.  Cathelecidin - the beta-Defensins - it also expresses Toll-like receptor 2. In addition to that, it expresses at least 913 genes, many connected to autoimmune diseases and cancers. So, by dysregulating and slowing the VDR, Epstein-Barr Virus and Mycobacterium tuberculosis have actually evolved to slow the body's very defense mechanisms that would otherwise be actively working to render them dead.
 ====#10 HIV and Borrelia burgdorferi====
-Note that HIV persists in the same fashion. It completely overtakes the VDR in order to transcribe its own genome.(({{pubmed>long:17556530}})) And, //Borrelia// (Bb) does as well.  Live Borrelia downregulates the receptor by about a factor of 50, lysed by a factor of 8.(({{pubmed>long:19461888}}))
+And note that HIV persists in the same fashion. It completely overtakes the VDR in order to transcribe its own genome.(({{pubmed>long:17556530}})) And, //Borrelia// (Bb) does as well.  Live Borrelia downregulates the receptor by about a factor of 50, lysed by about a factor of 8.(({{pubmed>long:19461888}}))
-This is such a logical survival mechanism on the part of these microbes that it is almost certain other less well-studied microbes have also evolved to slow VDR activity, or the activity of other receptors involved in controlling the immune response.
+So - this is such a logical survival mechanism on the part of these microbes that it's almost certain that other less well-studied microbes have also evolved to slow VDR activity, or the activity of other receptors involved in controlling the immune response.
 ====#11 Successive infection====
-Well, these persistence mechanisms result in a snowball effect. When the immune system slows, and a person acquires one pathogen, then it becomes easier to acquire another pathogen.  Then the immune system acquires another pathogen.  These pathogens - they can each slow the immune system in turn. They can be viral, bacterial, fungal... and so on and so on. And this process is referred to as successive infection.
+Well, these persistence mechanisms result in a snowball effect. When the immune system slows, and a person acquires one pathogen, then it becomes easier for them to acquire yet another pathogen.  And the immune system then acquires yet another pathogen.  And these pathogens each slow the immune system in turn. And the pathogens - they can be viral, fungal, bacterial... and so on and so on. And this process is referred to as successive infection.
 In the context of successive infection, an inflammatory disease state appears to result from the combined pathogenicity of the sum of microbes that any one person accumulates over the course of a lifetime. As human genes are upregulated or downregulated by components of these microbes, the human body shifts further and further away from its natural state of homeostasis.
 And, infected cells increasingly struggle to correctly produce human metabolites in the face of all the proteins and enzymes that are being created by the pathogenic microbes.	So, eventually, people either start to develop an inflammatory diagnosis such as one of the "autoimmune" diseases, or they simply begin to present with aches and pains and other symptoms of what is often deemed "normal" aging.
 ====#12 Epstein-Barr Virus (EBV)====

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