"The omega-3 PUFAs ***reduced expression levels of*** costimulatory molecules CD80 and CD86 and major histocompatibility complex ***HLA-DR.***
PMID: 17499970
It would appear, our body is saying, "Hey, this is an INTRAcellular pathogen. Get HLA-DR down and focus on HLA class 1 antigens instead!"
Since monocytes become macrophages and inflammation or EPA downregulate HLA-DR on monocytes...then the "mature" monocytes i.e., macrophages should regulate HLA class 1 antigens (A, B, C).
Once HLA DR is downregulated, we have to focus on HDL class 1 antigens (proteins) which are A, B, and C.
I highly suspect these correspond to Bb's antigens = proteins (OspA, OspB and OspC).
"The C receptor is a heterodimer consisting of a HLA-C mature gene product
*and β2-microglobulin*."
Me...HLA CB2?
KIR2DL1 has been shown to interact with HLA-C.
Killer cell immunoglobulin-like receptor 2DL1 is a protein that in humans is encoded by the KIR2DL1 gene.
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells.
Is Bb messing with our natural killer cells via inhibiting CB2/HLA C + B2?
Ancora Imparo! (Translation: I am still learning)
Posted by Keebler (Member # 12673) on :
- Thanks, Marnie. I have this gene type but have been to ill to really delve into the literature. Thanks for this so I can get cracking on it, finally. -
Posted by TerryK (Member # 8552) on :
Marnie -
OK, now I'm confused.
You wrote: People who have this gene type (HLA DR) are at a greater danger when it comes to lyme (takes more to downregulate it).
Doesn't everyone have HLA-DR? Isn't it the HLA-DR subtypes that determine various genetic factors?
You wrote: Because Bb goes INTRAcellular, it would thus be logical that HLA DR has to be downregulated.
Doen't HLA-DR identify and thereby help get rid of the toxins that are created by borrelia, mold, spider bites etc. etc...? We need HLA-DR to work for us to get rid of the toxins. That's my understanding.
Terry
Posted by TerryK (Member # 8552) on :
HLA-DR alleles determine responsiveness to Borrelia burgdorferi antigens in a mouse model of self-perpetuating arthritis.
Iliopoulou BP, Guerau-de-Arellano M, Huber BT. Tufts University, Boston, Massachusetts 02111, USA.
Abstract
OBJECTIVE: Arthritis is a prominent manifestation of Lyme disease, which is caused by infection with Borrelia burgdorferi (Bb). Chronic Lyme arthritis persisting even after antibiotic treatment is linked to HLA-DRB1*0401 (DR4) and related alleles. In contrast, patients whose Lyme arthritis resolves within 3 months postinfection show an increased frequency of HLA-DRB1*1101 (DR11).
The aim of this study was to analyze the underlying mechanism by which HLA-DR alleles confer genetic susceptibility or resistance to antibiotic-refractory Lyme arthritis.
METHODS: We generated DR11-transgenic (DR11-Tg) mice on a murine MHCII-/- background and compared their immune response to Bb antigens with the response of DR4-Tg mice after immunization with Bb outer surface protein A (OspA) or infection with live Bb.
RESULTS: T cells from OspA-immunized and Bb-infected DR11-Tg mice had defective production of interferon-gamma as compared with those from DR4-Tg mice. In contrast, DR11-Tg mice developed higher titers of anti-OspA and anti-Bb antibodies, respectively, than did DR4-Tg mice.
Consistent with this observation, we found that the Bb-infected DR11-Tg mice had a decreased spirochetal burden as compared with the DR4-Tg mice, as measured by quantitative polymerase chain reaction.
CONCLUSION: This study provides direct evidence that in the presence of HLA-DR11, the immune response against Bb antigens is directed toward a protective antibody response. In contrast, an inflammatory Th1 response is induced in the presence of DR4. These observations offer an explanation for the differential genetic susceptibility of DR4+ and DR11+ individuals to the development of chronic Lyme arthritis and, eventually, the progression to antibiotic-refractory Lyme arthritis. PMID: 19950279 [PubMed - indexed for MEDLINE]PMCID: PMC2828865 [Available on 2010/12/1]
Posted by Annelet (Member # 13503) on :
Dr K thinks that people with this genotype who have KPU/HPL issues actually detox much better when the Zinc and B6 deficiencies are treated.
Posted by TerryK (Member # 8552) on :
Ann, would you be so kind as to post a link if you have one so I can see if Dr. K mentions which subtype of HLA DR he is talking about? Sounds like maybe the detox one, not the one that is associated with refactory lyme arthritis?
I think anyone with the genes that Dr. S (Mold Warriors) mentions that cause the problem with detox stay sick because they can't detox borrelia toxins. Borrelia toxins will cause one to continue to experience the symptoms of lyme. The answer there is binders like cholestyramine.
Perhaps treatment for KPU helps make more antibodies that get rid of the toxins? I know that zinc is very helpful to the immune system.
I wonder if the reason KPU helps is because it helps detox heavy metals? We know that when borrelia dies it releases heavy metals. If one has problems detoxing heavy metals seems like KPU would help a lot.
ahhhh.... so many questions, so few answers.
Terry
Posted by Annelet (Member # 13503) on :
This is the presentation at the Lyme-Autism conference where Dr K mentions the detox issue. @ hours long, but i found it to be very interesting.
One thing that I found really interesting was how he tried to "think like a smart bug". Instead of trying to find multiple ways of interfering with immune function, why not trigger one thing that would have the desired end result....namely to somehow activate a "switch-off" that would get rid of all the zinc. Simplistic, I know....but it makes sense !
Zinc is crucial to an effectively working immune system.
![[Big Grin]](biggrin.gif)