I'm not convinced that genes are all that. There is one study I saw that said something like with identical twins one getting RA is 8% and both getting RA are only 15%. If genes were all that then that second number (actually both) would be MUCH higher. Plus, there are HBL-whatever gene info - supposedly if you had that, then you got RA - only as time went on, there were more people who had the gene and didn't get RA and those that didn't have the gene and did. Go figure. It's things like this that keep me coming back to some sort of 'trigger' and something the body cannot remove from the body easily - something it misses but keeps trying to hit. From what I can see - danger model, or infectious model, would expose you to the pathogen back in the day (very few studies say/threorize it can be passed on mother to child) and some sort of recent event would somehow 1) either reactivate the original pathogen or 2) add in some sort of secondary pathogen that would/could initiate the cascade called AI disease.
<snipped from links>
There is no reason why APCs should not respond to both endogenous and exogenous
signals. Vertebrates and bacteria have shared eons of evolutionary time and space, and
thus receptors for endogenous and exogenous signals may have evolved simultaneously.
Indeed, there is evidence that these receptors are often the same molecules. The answer was a little further on - I'll change what I consider important to green.
One possibility is that we may be looking at the PRRs completely backwards (
7). Perhaps PRRs have not evolved to bind to pathogens at all. Perhaps the pathogens have evolved to bind to them! Many cell surface molecules involved in normal physiological functions are targeted by pathogens. Human immunodeficiency virus, for example, binds to CD4, CCR5, and CxCR4, and Toxoplasma also seems to bind to CCR5 (30), whereas Staphylococcus and Streptococcus bind to a conserved loop on T cell receptors and to the Fc portion of antibodies. Coxsackie virus binds to intracellular cell adhesion molecule-1 (ICAM-1), rabies to N-CAM, and Epstein-Barr virus to complement receptor 2, thus activating a B cell as it enters. No one suggests that these molecules have evolved to act as receptors for pathogens. We assume instead that the pathogen's ability to bind to these molecules serves the pathogen's agenda, not ours. Similarly, the PRRs may be misnamed. For example, CD14, which recognizes apoptotic cells (31), has been called a PRR because it also binds to bacterial LPS (32). However, mice lacking CD14 resist Gramnegative bacteria more vigorously than their normal littermates (33), suggesting that the LPS-CD14 interaction is more favorable to the bacterium than to the host. -
So, this keeps bringing me back to the 'Borg/you will be assimilated' theory that once the infection/whatever becomes activated, it somehow 'hijacks' the cells it needs to survive. Usually (my opinion) is that there is some threshold that needs to happen so the body becomes 'unable' to fight back as it would normally. For some of us, that's the 'canary in the coal mine' aspect JSNM speaks of, with first the thyroid, then one AI disease, then another etc, until the body is so overwhelmed we die, my guess, usually by some cancer that they don't link to AI disease.
The long history of host–pathogen coevolutionary interactions has led pathogens to develop efficient tools for impairing the host immune system. Immunologists have much to learn from these pathogen strategies, which could help us to imagine and design new potent tools to control the immune response in various immunopathological conditions such as diabetes and related autoimmune diseases, graft rejection, or allergy. Pathogens, on the other hand, have evolved under a selective immune pressure that allows them to thrive whether or not they comprehend immunologist's models.
Basically, the models the scientists make don't really matter because the pathogen is going to do what it needs to do to survive. If the scientists can figure out what the pathogens are doing they can use that info to deal with other things like graft rejection, etc. She's wrong here - my personal opinion - in that some, if not most, diabetes is some sort of pathogen 'canary' affecting pancreas instead of the thyroid or adreanal system.
Transplants, however, cannot be performed without surgical and/or ischemic damage. Thus, to induce the acceptance of transplants without lifelong immunosuppression, we should mimic the body's own way of inducing tolerance, i.e., by blocking the endogenous alarm and/or costimulatory signals.
[/QUOTE]
The answer to the above was a bit further on -
Most of the current immunosuppressive drug protocols endeavor to block Signal One (antigen recognition). Although this effectively blindfolds the lymphocytes, it also prevents them from becoming tolerant, and consequently the drugs must be given for life. In contrast, studies in rodents and monkeys (
36-38) have shown that short-term treatment with costimulation blockers, or blockers of alarm signaling (39), can lead to long-term graft acceptance in the absence of long-term immunosuppression. Perhaps the lower extent of damage can explain why kidneys from living donors are accepted more easily than those from cadavers (4). Similarly, fetuses should not elicit immunity, in spite of being foreign, as long as they are healthy and do not send alarm signals (10).
I just found it interesting that they figured out a way to do this (in animal models) that doesn't require being on drugs for life. Hmmmm. Bet this goes nowhere.
The part about tumors I found fascinating especially since they have recently started using 'infection' as a way to get the body to shrink tumors. That's assuming, of course, that tumors aren't microbial in onset/nature.
This part about Autoimmune diseases -
In these cases, the immune system is not at fault; it is doing its job of responding to alarm signals (but, in these cases, to the detriment of the host). If we could pinpoint these mutations or environmental agents, we might be able to reduce the incidence ofautoimmune diseases. No duh, this is exactly what I think is going on. Our bodies are doing exactly what it needs to do to try and protect us long term. It's hurts and isn't pleasant (understatement) but it's doing what it's supposed to do. The only question I had was what could I do to help it along so it can 'recover' enough to fight back on it's own.
Anyway - the part that got me the most excited was the stuff about how the specific tissue effected (RA would be joint) etc determines the cellular response. Which, in my mind, makes the genes even less relevant and ties this more to Dr. Brown's original theory in that that microbe itself really didn't matter because almost all disease was different manifestations of the same thing - microbial infection. So, a microbe that prefers the spine is going to lodge there. And the rheumies are going to say 'splondyarthy'. And if it lodges in the joint - its RA. If it lodges in the pancreas - it's diabetes. And when it moves on...it's yet another 'separate' disease, seen by a different doc - but its all the same original problem.
And I loved the stuff about endogenous stress molecules - especially since I fell in love with the HPA axis.
Anyway, I've been gone all day ice skating (first time since I damaged my rib) and I'm exhausted. Your turn, girls.
Pip
Pip, great article - I have been the one going WTF?, that your immune system (which is to protect you) suddenly for no reason whatsoever (like an infection too powerful to overcome?) turns on itself and starts to attack your own body. One of your defense systems suddenly decides it time to do a 180 and do the opposite of what its suppose to do? I just haven't bought into the "approved AMA only way it can be" theory about autoimmune and autoimmune diseases. It going to take me a LONNNGGGGGG time to fully understand this article. Once again, thanks for all your great research. Cathyhow about this thought...
young children can be transplanted and not have lifelong immunosuppression. Their bodies adapt to the new organ. So maybe the rejection in adults isn't because of the organ itself but that the doner heart tissues bears traces of every antigen the doner has ever been exposed to and its these new antigens that cause the rejection response in the recipiant. it works with the infection theories
Yes, the danger model, which I still only partially understand, is compatible with the infection theory model. And I've dragged this link out a few times but it's relevant her again:
http://www.med.umich.edu/opm/newspage/2007/microbes.htm
On a more personal note, the day I got DXed and my RD explained to me that the theory was for no apparent reason, other than maybe, a genetic predisposition, my immune system uped one day and started attacking myself, I almost laughed in her face (and I do have a lot of respect for my RD). I never believed it for a minute.[QUOTE=SnowOwl]
Ok, bear with me. I'm not feeling so great today and am not the brightest bulb in the chandelier. So, let's say autoimmune diseases, plural, boil down to being an individual's immune response to any or every "danger" that triggers overreaction to infiltration. Is it practical that we could learn to identify and counter-attack specific exogenous causes? You're looking at environmental triggers, bacterial agents, food allergies, reactions that approach infinite as they mutate and new strains develop of viruses? From what I've read and comprehend (and that's not much), the best treatment candidate to date still seems to lie in the refinement of stem cell therapy, where does that fit in to the Danger Model theory?
[/QUOTE]
Snow -
Yes it's possible to counter specific causes - but that is just more therapies. I'm thinking what we need to do is help the body do what its trying to do. I've found research that says certain substances can 'correct' or 'mend' cellular degeneration or receptors that go bad (for want of a better term). This is part of the reason I've been focused on my sleep patterns because that's when the body heals best. If we can undo the cellular damage then we can heal. Or be cured. Which they tell is isn't possible. As for stem cell therapy, I'm assuming that they will attempt to find some sort of gene therapy that they can inject that will instantaneously fix whats wrong. We are a 'magic little pill' society and how many people here on AI are willing to change eating habits etc to get the body repaired? Not a lot (self included but I'm still psyching myself up for it - sigh). With stem cell therapy, right now that's for the 'end of the road' people. This would fit in with the Danger Model because if they can remove a pathogen and reboot the body - of course people would be cured. Right now, the problem is that many, if not most, cell lines are contaminated. Google that - what a nasty surprise. And it might be the reason why in a 1/3 of the cases the disease comes back.
GoGo -
I love that post - I use it all the time to visualize what I'm trying to kill off. Kind of Pac-man like. LOL
Buckeye -
<blink, blink>
What? Kids don't have to immunosuppress? Are you sure? Is there an age cut off? And yes, that would tie into the infection theory. Also, did you understand that part about how they can get the body to accept a transplant with rats etc? Can you explain that better than I did?
Pip
Pip, don't want to get OT, but gluten free isn't really that bad, once you get through the adjustment period. You can make great cakes and stuff with rice flour (use less). I can send you some awesome pancakes and cashew sauce recipes so yummy you'll wonder why people eat gluten.
No, I am not gluten free but I know many people who are, and I "practice" often.I'll get those recipes from you soon, please.
And bump.
Pip
Pip..I'm talking very young children..age measured in months not years. Most pfteb children born with severe heart problems. They can be transplancted with hearts not of the same blood type and they don't reject.
I'll have to reread the article before I try to answer the rat thing
whoa.. buckeye! That's really interesting.Here is the twin studies and RA.
http://www.sciencedaily.com/videos/2007/0711-identical_twins_identical_problems.htm
Until someone else acknowledges this study I don't think it means much.bumpAcknowledges it how, Anna? He's saying the same thing - 15%. You'd think it would be more. What I found interesting is -
The research team thinks these genes are susceptible to something called oxidative stress, which affects how cells repair themselves. But there's only a small chance it will trigger the disease, which is why most of the time, only one twin inherits the disease.
And -
Every cell or tissue has the same genetic information; what differentiates them is that in each, different sets of genes that are turned on, or “expressed.” Epigenetic marks are chemical additions to the DNA sequence that turn genes on or off.
This guy wants to make more therapies - it says so in the article - he's not even looking for the 'cure' or 'what's causing this'.
Certain natural compound found in every day foods can re-write genes and turn things off. We just need to figure out how to help the body heal so it does.
Pip
Bumping for JSNMtanks I remember my eyeballs rolling back trying to read this one. Keep at it - seriously, this is the 'one' I think, that's most on the money. Brings in all the theories together and accounts for a lot. She's also updated her theory - no - I have no idea where I put that either.
Pip
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