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Hepatitis Researcher importance of TH1 response
I aked you before in a previous post what, if any, your thoughts were in regards to SVR and a vigorous TH1 favored immune response. I'm started to beleive that it is exactly this shift from the dominating Th2 response to a more 'viral hungry" TH1 response which determines svr at the end of treatment. In other words, people who acheive svr are also maintaining a strong Th1 response at the end of treatment which in turn may be keeping any viral remnants in check. People who fail to acheive svr maybe reverting back to the old virally favorable TH2 arm of the immune system when the drugs are removed from their systems. Do you think my hypothesis is credible?
and it looks like you passed with flying colors! our gain!
and thank you for sharing your time here. Coming to this site gets addictive sometimes, I am still trying to cut back...
I hope you find the time to continue.
be well
and thank you for sharing your time here. Coming to this site gets addictive sometimes, I am still trying to cut back...
I hope you find the time to continue.
be well
MEDICAL PROFESSIONAL
yes HR spoke with Cindy, to clarify his position in hepatitis research.
what happened to comment 4, posted by MH? did our friend HR speak with Cindy?
MEDICAL PROFESSIONAL
The Th 2- Th1 balance concept in immunology is a broad principle that is based on original findings in mice that states that a preponderance of Antibody responses and cytokines ( Il-4 and Il-10) supporting B cell and Ab responses is calles Th2. It is less agressive to the tissues and a defense system against invading pathogens - like soluble antigens and Toxins that can be neutralized by Antibodies.
We are born with a Th2 preponderance.Then by contact with bacteria a natural Th1 shift takes place. If too much hygiene, the shift is prevented and Allergies and Asthma are the consequences....
Once an organism , bacteria or viruses, have penetrated inside host tissues a new form of defense has to be activated to eliminate or kill intracellular microorganisms, even if that means to kill the invaded cell. The cytokines ( Gamma and alpha Interferons, Interleukin 12, Il-1 and many more) stimulate agressive intracellular defense mechanisms as well as cellular immune responses which lead to infiltration, local cytokine production and target specific cytotoxic T cell proliferation and activation which allow the immune system to regognize intracellular antigens by seeing spefic fragments of those - 10mer peptides) on the surface of the infected cells presented by MHC class I presenting molecules.
All in all the Th1 response is much more painful for the host, but necessary to eliminate or reduce the infection once it has advanced to such a stage.
Activation of the TH1 mode of reactivity occurs mostly by regognition of molecular patterns of invading organism by Dendritic cells and Macrophages on their so called " Toll like receptors". These cells in turn activate T helper lymphocytes to assume the "Th1 phenotype" characterized by the above mentioned cytokine secretion patterns. The rest of the response is thus " shifted " towards a "Th1 type".
In HCV therapy the general importance of inducing such a shift is well regognized.
1. Coleys Actilon trials of CpG 10101 together with IFN are the most direct attempt to directly activate the Th1 mode and are quite successfull so far. Anybody here participating in their trial?? this CpG 10101 directly acts upon TLR 9 on dendritic cells, induccing them among other things to produce an enormous amount of IFNalpha directly PLUS inducing the Th1 pathway.
2. Ribavirins action is assumed by many to include a selective activation of the Th1 arm of immune responses.
3. Substances found in maitake, shitake and reishi mushrooms are also mimics of "natural" Toll like receptor stimulators and induce, at least in mice, such a redirection. The extent, toxicity and usefulness of these stimulators is however not well researched - some of these might be good add ons to conventional therapy others might be useless or do more harm than good. Any extract of this nature has to be standardized and it is a long way from "proof of principle" to controlled clinical trials. There are some trials, mostly in China.
4. Thymosin alpha aka Zadaxin is in phase III trials for use in HCV and has a Th1 stimulating activity as part of its action profile.
5. Trials using Interleukin-12 ( the most direct Th-1 shifter) have been performed in HCV as monotherapy, but have not shown clear benefit. The immunological reality is very very complex...
We are born with a Th2 preponderance.Then by contact with bacteria a natural Th1 shift takes place. If too much hygiene, the shift is prevented and Allergies and Asthma are the consequences....
Once an organism , bacteria or viruses, have penetrated inside host tissues a new form of defense has to be activated to eliminate or kill intracellular microorganisms, even if that means to kill the invaded cell. The cytokines ( Gamma and alpha Interferons, Interleukin 12, Il-1 and many more) stimulate agressive intracellular defense mechanisms as well as cellular immune responses which lead to infiltration, local cytokine production and target specific cytotoxic T cell proliferation and activation which allow the immune system to regognize intracellular antigens by seeing spefic fragments of those - 10mer peptides) on the surface of the infected cells presented by MHC class I presenting molecules.
All in all the Th1 response is much more painful for the host, but necessary to eliminate or reduce the infection once it has advanced to such a stage.
Activation of the TH1 mode of reactivity occurs mostly by regognition of molecular patterns of invading organism by Dendritic cells and Macrophages on their so called " Toll like receptors". These cells in turn activate T helper lymphocytes to assume the "Th1 phenotype" characterized by the above mentioned cytokine secretion patterns. The rest of the response is thus " shifted " towards a "Th1 type".
In HCV therapy the general importance of inducing such a shift is well regognized.
1. Coleys Actilon trials of CpG 10101 together with IFN are the most direct attempt to directly activate the Th1 mode and are quite successfull so far. Anybody here participating in their trial?? this CpG 10101 directly acts upon TLR 9 on dendritic cells, induccing them among other things to produce an enormous amount of IFNalpha directly PLUS inducing the Th1 pathway.
2. Ribavirins action is assumed by many to include a selective activation of the Th1 arm of immune responses.
3. Substances found in maitake, shitake and reishi mushrooms are also mimics of "natural" Toll like receptor stimulators and induce, at least in mice, such a redirection. The extent, toxicity and usefulness of these stimulators is however not well researched - some of these might be good add ons to conventional therapy others might be useless or do more harm than good. Any extract of this nature has to be standardized and it is a long way from "proof of principle" to controlled clinical trials. There are some trials, mostly in China.
4. Thymosin alpha aka Zadaxin is in phase III trials for use in HCV and has a Th1 stimulating activity as part of its action profile.
5. Trials using Interleukin-12 ( the most direct Th-1 shifter) have been performed in HCV as monotherapy, but have not shown clear benefit. The immunological reality is very very complex...
Another interesting view on th1/th2
http://www.planetpoz.org/education/period/pozhealth18.html
http://www.planetpoz.org/education/period/pozhealth18.html
This link supplements the above question about TH1/TH2 BALANCE AND FACTORS RELATED TO IT.
http://www.diagnose-me.com/cond/C104791.html
http://www.diagnose-me.com/cond/C104791.html
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