Topic: What does HSV-1 and Bb have in common...this!
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
If you don't want to read any further...just read the next sentence.
Both HSV-1 and Bb downregulate an antigen (protein) called CD1d.
Now for those who are interested in further learning with quotes from research (not linked to make this easier to read)...keep reading.
HSV-1 is the virus that causes cold sores. It goes dormant when our immune system is functioning well. It "rests" in nerves near our ears.
"NKT cells are involved in initial responses to viruses, and we recently showed that herpes simplex virus type 1 (HSV-1) escapes recognition by
inducing the down-regulation of CD1d molecules from the surface of infected cells ,
including DCs. The virus prevents reexpression of CD1d molecules on the cell surface during the normal process of recycling through the endocytic pathway."
J Immunol. 2000 Nov 1;165 (9):4797-801 11046002
"Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi.
H Kumar , A Belperron , S W Barthold , L K Bockenstedt
CD1 molecules can present microbial lipid Ag (Ag = antigen - a protein) to T cells, suggesting that they participate in host defense against pathogens.
In this study, we examined the role of CD1d in resistance to infection with the Lyme disease spirochete, Borrelia burgdorferi (Bb), an organism
*with proinflammatory lipid Ag.*
Bb infection of CD1d-deficient (CD1d(-/-)) mouse strains normally resistant to this pathogen resulted in arthritis.
Pathology correlated with an increased prevalence of spirochete DNA in tissues and enhanced production of Bb-specific IgG, including IgG to Ag rapidly down-modulated on spirochetes in vivo.
CD1d(-/-) mice exhibited high-titer Bb-specific IgG2a, an isotype commonly induced in disease-susceptible mice but not in the disease-resistant control mice in this study.
These results show that CD1d deficiency impairs host resistance to a spirochete pathogen, and are the first example of a mutation that imparts Bb-resistant mice with the Ab and disease profile of a susceptible mouse strain."
It appears Bb's PKC inhibitor (IF it is indeed PKC delta) does exactly the same, i.e., downregulates the CD1d molecule because...
"Protein kinase C delta is a critical regulator of CD1d-mediated antigen presentation."
Without PKC delta (if Bb's PKC inhibitor is PKCD) ...CD1d antigen presentation is kapoot.
What is that molecule?
"T-cell surface glycoprotein CD1d antigen, bound to phosphatidylcholine." (An antigen is a protein.)
The above indicates a glucose - glyco (sugar) and fat connection.
A PKC (protein kinase C) delta inhibitor prevents the T cells from reacting to the CD1d antigen which binds to...phosphatidylcholine.
Phosphatidylcholine is LECITHIN...a fat EMULSIFIER.
"The initial immune response to any antigen absolutely requires that the antigen be recognized by a T lymphocyte ("T cell")."
"Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer (NK) cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self- and foreign lipids and glycolipids. They constitute only 0.2% of all peripheral blood T cells."
"Natural killer T (NKT) cells should not be confused with natural killer (NK) cells."
"NKT cells are a subset of T cells that co-express an alpha beta T cell receptor (TCR), but also express a variety of molecular markers that are typically associated with NK cells, such as NK1.1.
They differ from conventional alpha beta T cells in that their TCRs are far more limited in diversity and in that they recognize lipids and glycolipids presented by CD1d molecules , a member of the CD1 family of antigen presenting molecules, rather than peptide-MHC complexes."
"NKT cells seem to be essential for several aspects of immunity because their
dysfunction or deficiency has been shown to lead to the development of autoimmune diseases (such as diabetes or atherosclerosis) and cancers."
"Both CD1d Antigen Presentation and Interleukin-12 Are Required To Activate Natural Killer T Cells."
CD1d deficiency is also linked to lupus:
"Germline deletion of CD1d exacerbates lupus in BWF1 mice."
"Macrophages are believed to help cancer cell proliferate as well.
They are attracted to oxygen-starved (hypoxia) tumour cells and promote chronic inflammation.
Inflammatory compounds such as Tumor necrosis factor (TNF) released by the macrophage activates the gene switch nuclear factor-kappa B. NF-kB then enters the nucleus of a tumour cell and turns on production of proteins that stop apoptosis (cell death) and promote cell proliferation and inflammation."
NKT cells have recently been implicated in the disease progression of human asthma."
"CD1d is crucial in the priming of SEA-specific Th2 lymphocytes."
Hence...Th1 up, Th2 down. Th1 downregulates Th2.
MOre...
"Only B. burgdorferi elicited gamma interferon (IFN-gamma) from NK cells. B. burgdorferi was phagocytosed avidly by monocytes.
Depletion of monocytes revealed that they were the primary source of inflammatory cytokines , while dendritic cells (DCs) directed IFN-γ production from innate lymphocytes."
Langerhans cells are dendritic cells.
"During infection, circulating blood monocytes migrate from the vasculature to the extravascular compartments where they mature into tissue macrophages ,"
"Thus, phagocytosis of live spirochetes initiates cell activation programs in monocytes and DCs that differ qualitatively and quantitatively from those induced at the cell surface by lipoprotein-enriched lysates."
(Macrophages - many kinds - live from months to years and are more abundant in fat cells. Think of them as pac-men...gobbling up pathogens.)
Activated gamma delta T cells, on the other hand, are able to exert an influence on B cells by
inhibiting the secretion of IgG in coculture experiments."
Bottom line and greatly simplified..."delta" is being downregulated. Bb prevents our immune cells from recognizing/reacting to a protein named CD1d which binds to phosphatidylcholine...lecithin.
I have been doing a lot more research getting into FABP4 (fatty acid binding protein 4 adipocyte), PPARd and PPARy - delta and gamma because:
I'm trying hard to figure out how to get our system to recognize CD1d and respond accordingly.
Meanwhile...I am also researching cAMP...bigtime because I believe that may well be the "protein or enzyme in the blood of the WFL" that confers protection.
Somehow, this all links together:
"The PKC delta-like protein is phosphorylated in vivo in response to cAMP and phorbol ester stimulation."
and...
"Here we report that cAMP-induced effects in Th2 cells occur independently of the protein kinase A pathway, which is the major mediator of cAMP-induced signaling events in most cell types.
Instead, cAMP stimulates activation of p38 mitogen-activated protein kinase in Th2 cells. This appears to be a Th2-selective event because cAMP barely increased p38 phosphorylation in Th1 cells."
and...
"There is considerable interest in the possible use of cAMP-elevating agents in the treatment of autoimmune diseases such as rheumatoid arthritis.
"The cAMP-elevating agents could directly influence the activity of T cells but, in addition,
influenced the ability of antigen-presenting cells to support T helper type 1 responses."
Last but not least...now THIS IS WEIRD...
CD1D 16
In Gene Array layout...
There's 16 again!!!
H16...group...vascular damage...
Ancora Imparo!
Pycnogenol. Forskolin. Curcumin. Ecklonia cava in Fibronol...(acetylcholinesterase implications in addition!)
I only have been told (by a retired ID doctor) and have research to back up the dosage of Pycnogenol(Arizona, asthma)...1mg per pound of body weight per day.
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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bejoy
Frequent Contributor (1K+ posts)
Member # 11129
posted
Very interesting.
Connection questions:
Isn't phosphatidylcholine used to reduce cortisol levels?
Could this begin to explain some of the hormone dysregulation that happens to so many people with lyme?
-------------------- bejoy!
"Do not go where the path may lead; go instead where there is no path and leave a trail." -Ralph Waldo Emerson Posts: 1918 | From Alive and Well! | Registered: Feb 2007
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
No...to restore the HPA axis = phosphatidyl serine.
Hypothalamus, pituitary, adrenal = HPA.
Pretty significant doses.
The neurohormones and neurotransmitters "signal" each other.
Bb has a gene for C-acetyltransferase. It is using this enzyme...depleting it, it appears.
That enzyme is needed to make acetylcholine.
When acetylcholine levels drop...others go up.
The imbalances are HUGE in lyme...and MANY.
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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posted
How do we get more phosphatidyl serine to restore the HPA axis?
Posts: 172 | Registered: Dec 2003
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clairenotes
Frequent Contributor (1K+ posts)
Member # 10392
posted
I am not sure which foods might provide more phosphatidyl serine, but my husband uses a Jarrow brand and I just purchased a Designs For Health product. My husband notices a big difference in mental clarity. I haven't tried either product yet. In fact, I almost forgot that I purchased the DFH product... so I think I am anxious to try it .
Thanks for the information, Marnie. I will have to go back and re-read it later.
Claire
Posts: 1111 | From Colorado | Registered: Oct 2006
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Forskolin is a PDE4 inhibitor. It increases cAMP (it looks to do so by preventing its breakdown, I think - preventing the enzyme that breaks down cAMP to AMP).
Phosphatidyl Serine comes as a supplement.
Apparently 300mg is the "magic" dose. I don't know why. More doesn't make a difference from what I've read.
Now...it is usually recommended to take it in divided doses, but someone here took it all at once and reported (here) s/he felt better.
IMO there is just too much oxidative stress happening. We need some, but not so much!
Try Pycnogenol also at doses of 1mg per # of body weight all at once, one time a day...and report back. In other words, if you weigh 150#s, you'd be taking 150mg. Sorry...it is not a cheap one either.
The source is important. It must come from FRENCH PINE TREE BARK.
The supplement companies are unregulated and as such, not all are "created equal". It is important to know the reputable companies. (Same hold true for Curcumin sources.)
I noticed a HUGE difference (no more "restless legs")now that I am taking Pycnogenol daily. I don't have great leg circulation (genetic - dad too). My son is using it too and also reports that he "thinks clearer".
It was recommended by a very smart retired ID doc here...so I feel confident enough to post!
He stays abreast of research! Not so all docs.
Ultimately though...because of acetylcholinesterase (enzyme that breaks down acetylcholine)...Fibronol may be the best IF the company is "legit".
Too many free radicals impact our immune system - negatively - ALSO.
Let's see if I can simplify this...Bb has a PKC inhibitor. Tamoxifen is a man-made PKC inhibitor that is used to DESTROY breast cancer cells.
It looks like the objective of PKC inhibitors is to harm cells.
Bb's PKC inhibitor looks to harm our immune system cells (Langerhans and macrophages themselves become infected and can't function as they should)...from the get-go.
(Macrophages come from monocytes. Macrophages live in our system for months to years...)
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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