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Aussie Barb
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Posted: Thu Mar 24th, 2005 07:36 |
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What is the basic definition of Th1 inflammation?
This tutorial contains basic information on T-Helper cells.
"Th1 is short hand for "T-helper cell type 1" which is a state of activated CD4+ T lymphocytes thought to be behind an immune response which is characterized by a cytokine profile slightly different from the body's normal response to viruses, funguses, etc, a profile which is strong in a cytokine called Interferon-gamma.
Th2 response is activated by the cytokine storm from the Th1 pathogens, this is why we have the 'autoimmune' antibodies which have distracted medicine for so long. The Th2 immune reaction of a healthy body does not generate much Interferon-gamma.
This is important, as the Th1 immune reactions often are thought of as an 'over-active' immune system, because the Interferon gamma, and the 1,25-dihydroxyvitamin-D it generates, cause extra mast cells to differentiate to monocytes (primitive white cells) and then to further differentiate (grow) into macrophages and dendritic cells, the most active phagocytes of the immune system, those cells which are charged with the job of digesting bacterial pathogens.
What I discovered was that when the phagocytes themselves become parasitized by CWD variants of certain bacterial pathogens, it is the pathogens which determine the body's immune response, not the T lymphocytes. The Th1 lymphocyte excitation is really a result of the intra-cellular infection, and not a response to extra-cellular bacteria. This is because the bacteria within the cytoplasm of the phagocyte can directly force the nucleus of that cell to produce the Th1 cytokines, presumably as an advanced defense against the host (human).
There is more info about this in our paper "Sarcoidosis succumbs to antibiotics - implications for autoimmune disease" at URL http://tinyurl.com/5rgmq
The free full text of that paper is available at
http://yarcrip.com/sarcoidosissuccumbs-preprint.htm
I hope this helps, it is quite a complex topic, and the solution had eluded science for at least 50 years "
As for Th1 and Th2, it takes a real scientist to cut through all the pseudo-science and be able to understand the underlying biochemistry which differentiates the two conditions. The Th1 diseases are defined to be characterized by high levels of Interferon-gamma in the inflamed tissue and it catalyzes production of 1,25-D by the mitochondria of the activated macrophages.
Common mistakes made by those who are confused between Th1 and Th2 include trying to measure the cytokines in venous blood (not in the paracrine tissue), not measuring Interferon-gamma but trying to make inference from something else, and making pronouncements when they don't have a clue about the underlying molecular medicine."
Dr. Trevor Marshall, Ph.D.
For more information about the Immune System you can order the DVDs 'Recovering from Chronic Disease' derived from our Chicago Conference @ our AutoImmunity Research Website. Here Dr Marshall explains how the immune system is perverted by the bacteria. and the "Familial Aggregation" presentation also deals with the genetic predisposition issue in detail.
Dr. Marshall's latest peer-reviewed paper contains the following definition of Th1 inflammation:
"The T-helper Type 1 (Th1) immune response is usually defined as one which generates significant quantities of the cytokine Interferon-gamma[10]. Many chronic diseases are associated with Th1 inflammation[11], including atherosclerosis[12], diabetes[13], and perhaps even asthma[14].
Generation of Interferon-gamma in a Th1 activated macrophage catalyzes its mitochondrial production of the secosteroid hormone 1,25dihydroxycholecalciferol (1,25-D) by as much as 30-fold[15]. 1,25D is the active secosteroid of the Vitamin D metabolism."
10. Raz E, Tighe H, Sato Y, Corr M, Dudler JA, Roman M, Swain SL, Spiegelberg HL, Carson DA: Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc Natl Acad Sci U S A. 1996 May 14;93(10):5141-5145.
11. Cantorna MT, Zhu Y, Froicu M, Wittke A: Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1717S-20S.
12. Mallat Z, Ait-Oufella H, Tedgui A: Regulatory T cell responses: potential role in the control of atherosclerosis. Curr Opin Lipidol. 2005 Oct;16(5):518-24.
13. Yoon JW, Jun HS: Autoimmune destruction of pancreatic Beta cells. Am J Ther. 2005 Nov-Dec;12(6):580-91.
14. Wittke A, Weaver V, Mahon BD, August A, Cantorna MT: Vitamin D receptor-deficient mice fail to develop experimental allergic asthma. J Immunol. 2004 Sep 1;173(5):3432-6.
15. Dusso AS, Kamimura S, Gallieni M, Zhong M, Negrea L, Shapiro S, Slatopolsky E: gamma-Interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: a mechanism for the hypercalcemia of various granulomatoses. J Clin Endocrinol Metab. 1997 Jul;82(7):222232.
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Acute inflammation can be a good thing for tissue damage since it isolates the damaged area, promotes the mobilization of effector cells and molecules to the area that can fight infections and injury, and then promotes healing.
Chronic inflammation (that is unsuccessful in promoting healing) can be viewed in a certain sense as inappropriate and can be detrimental to the organism since it can cause damage and loss of function.
-We ideally want an appropriate inflammation that heals the damage and kills invaders in a reasonably short time. Since the CWD forms can evade attack by living in the cells sent to kill them, we need a way to overcome this very successful strategy of theirs.
This way has proven to be the MP, in at least a great many people. ~P.B. RN
The immune system is both non-functioning and over-functioning
Many people think of the immune system as being some sort of automobile, all carefully planned and assembled, with all the parts working together in coordination.
But the human immune system is not like that. It has assembled itself over eons, with bits from here, pieces from here, and each function which has persisted has done so because it has improved the survivability of the host. Yet our immune system is not that much different from a fruitfly, for example.
http://www.quest.nasa.gov/projects/flies/flyImmune.html
The part of the immune system which is perverted by the Th1 pathogens is the innate immune system, the last line of defense. When phagocytosis fails to kill invaders, other parts of the immune system sense there is something wrong, and they go into overdrive trying to help out. But they cannot help the phagocytes get the innate immune system functioning properly again. This is what gives rise to chronic disease. So you see there is both non-functioning and over-functioning.
The part which is not functioning is the VDR, or Vitamin D Receptor, which is responsible for transcribing between 1000 and 27,000 genes. The VDR is blocked by the intra-phagocytic bacteria, as they need to block it from producing the body's anti-microbial peptides, which kill invading organisms. When they block the VDR they also take out a stack of other important functions the VDR would normally perform.
..Trevor..
Exogenous Vitamin D is an immunosuppressive seco-steroid. See our recent paper
http://TrevorMarshall.com/BioEssays-Feb08-Marshall-Preprint.pdf
Aldosterone is also a steroid and will further confuse your nuclear receptor signalling, and thus both your innate and adaptive immune system functions.
If you don't already understand this, then you really shouldn't be bothering your mind with the dichotomy between Th1 and Th2 events, which, in any case, are highly interdepent.
CFS is a Th1 disease, as the transcription of antimicrobial peptides by the VDR Nuclear Receptor is inhibited by the pathogens (see above paper). This lack of transcription is associated with an excess of Interferon-gamma (the Th1 marker). That is all you need to know.
I have seen none of the autoimmune or idiopathic conditions which are solely Th2 in origin. Any activity of the Th2 cytokines in chronic disease is a result of the primary Th1-inducing pathogens. There are a lot of scientific careers which are laid to waste by that statement, I am afraid, and therefore significant resistance to its acceptance in the scientific community at large...
(none of whom apparently feel solid enough in their own knowledge to engage in a public debate  )
..Trevor.. April 08
Last edited on Wed Aug 27th, 2008 03:24 by
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Barb: Dx Inflammatory Disease Endocrine Imbalance 2003| Depression| 24+ years not Dx| MP Aug04| ABC of MP| MP Search|
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Posted: Sat Mar 4th, 2006 07:18 |
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Do immunecells travel around in the whole body or do they stay in one place? filelink
-"A phagocyte is a cell that attracts (by chemotaxis), adheres to, engulfs, and ingests foreign bodies. Promonocytes are made in the bone marrow, after which they are released into the blood and called circulating monocytes, which eventually mature into macrophages."
-"Some macrophages are concentrated in the lungs, liver (Kupffer cells), lining of the lymph nodes and spleen, brain microglia, kidney mesoangial cells, synovial A cells, and osteoclasts. They are long-lived, depend on mitochondria for energy, and are best at attacking dead cells and pathogens capable of living within cells."
-"The non-fixed or wandering macrophages roam the blood vessels and can even leave them to go to an infection site where they destroy dead tissue and pathogens."
-"Natural killer cells move in the blood and lymph to lyse (cause to burst) cancer cells and virus-infected body cells."
For more info, see this tutorial about the immune system.
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Posted: Thu Sep 14th, 2006 06:41 |
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The meaning of 'autoimmunity'
(filelink)
Your immune system doesn't necessarily get weaker with age. The disease you have had since birth has caused it to weaken in your case. When the MP takes you to recovery your immune system will be working fine again.
The cause of 'autoimmune' disease has nothing to do with antibodies, or with adaptive immunity at all, those are just incidental road-kill to the key intraphagocytic pathogens, which can only be addressed by the innate immune system.
Our paper at the International Autoimmunity Conference in Budapest basically argued that 'autoimmunity' does not exist. I argued that the body is reacting to pathogens, not to itself. There were many there who agreed with me. Which does explain, of course, why folks don't immediately collapse in a heap of antibodies when they are diagnosed with 'autoimmune disease'. I believe that it stands to reason that if the body were actually attacking itself, it would do a better job of it, and the patient would die pretty quickly.
Antibodies are present in many of the diseases the MP addresses (eg RA, Lupus) and I never considered that they would be absent, once the SED rate rises as the bacteria start being killed.
Antibodies are not the cause of the disease state, they are a by-product of the key inflammatory process. Hence the concept of 'autoimmunity' is meaningless.
..Trevor..
The video of Dr. Marshall's presentation at Bio21 is now online at URL
http://autoimmunityresearch.org/bio21.ram
Note particularly the new slide at 10:45 into the presentation, explaining why antibodies are not what makes Th1 patients so sick.
Marshall TG: VDR Nuclear Receptor Competence is the Key to Recovery from Chronic Inflammatory and Autoimmune Disease. Abstract presentation, Days of molecular medicine, 2006. Copy available from URL http://autoimmunityresearch.org/karolinska-handout.pdf
Antinuclear Antibody tests
I regard the ANA tests as largely irrelevant. They are not specific enough to be useful as Th1 disease markers. Indeed, ANA disappear as the infection progresses. Many of the sarcies have had ANA disappear over the years, to be replaced by biopsy-verifiable granuloma.
What role do antibodies play in disease?
In 2004 I was honored to travel to Budapest to make a presentation on our work to the International Autoimmunity Conference there.
At the conference, the delegates were given a copy of a new book "Infection and Autoimmunity" (ed: Shoenfeld & Rose, ISBN 0-444-51271-3). Its 747 pages are packed with papers from researchers who were trying to look beyond the pragma of autoimmunity being caused by "antibodies to self." None of the contributors had hit the jackpot as we had done, but it makes interesting reading, as it does give the answer to the question "There is no doubt that these autoantibodies exist, is there?."
At Karolinska in May 2006 Laureate Rolf Zinkernagel gave the keynote. Rolf has dedicated his recent research to showing that disease is not caused by "antibodies to self." You can find a discussion of the significance of his recent work in this thread:
http://www.marshallprotocol.com/forum39/6896.html
At this point I have a definitive model, based in molecular biology, for the disease process leading to the syndromes we call "autoimmune." Our latest transcriptional-level model of the human Vitamin D metabolism is described in our paper which is currently 'in press', and part is also in my presentation at the recent Metagenomics conference
http://www.marshallprotocol.com/forum39/9348.html
The model shows that antibodies play no part in producing these syndromes. They become a player due to the cytokine and chemokine cascade after the intraphagocytic pathogens have done the actual damage via the innate immune system functions which they directly compromise.
During Th1 infection, antibodies are produced which have no obvious target. Some of these have been identified as "autoantibodies," antibodies directed at self. I am sure that science will eventually be able to find the true targets of these, and that they will be pathogen-related, not self-related.
..Trevor..Last edited on Thu Aug 23rd, 2007 19:36 by Foundation Staff
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