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Immune T cells help repair sore muscles after repeat exercise

Discussion in 'Other Health News and Research' started by Marco, Feb 9, 2016.

  1. Marco

    Marco Grrrrrrr!

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    At least that's how it's supposed to work:)

    It's not news that the immune system recognises and responds to mechanical damage as well as damage caused by pathogens (see DAMPS and PAMPS) but what may be new is identifying the role of T cells in 'remembering exercise induced damage'.

    http://www.medicaldaily.com/immune-system-sore-muscles-inflammation-working-out-372626
     
  2. roller

    roller wiggle jiggle

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    i understand, the big news was, that they detected t-cells in muscles... for the first time ...

    and that only because the graduate gave it a go...

    until then they 'thought' there were none...
     
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  3. anciendaze

    anciendaze Senior Member

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    Note that this is how the process is thought to work in healthy exercise. There are many ways such repair mechanisms can go wrong. I think this supports a connection with B-cell signalling to T-cells to limit recruitment, which has turned up in autoinflammatory disease.
     
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  4. Marco

    Marco Grrrrrrr!

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    @anciendaze Interesting. I was considering reduced T cell recruitment interfering with normal repair mechanisms but (having just skimmed it - bookmarked for later) that paper suggests the opposite.

    I wonder what @Jonathan Edwards thinks of this MO for the effects of B cell depletion in RA?

     
  5. roller

    roller wiggle jiggle

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  6. anciendaze

    anciendaze Senior Member

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    The problem I'm thinking about is that the normal repair mechanism works initially, but the signalling feedback to terminate the inflammation process is defective. At later stages I would expect some specific kind of immune exhaustion to limit a runaway response.

    Note that biochemical signalling during repair is likely to produce the subjective fatigue which limits physical activity until repair is complete. Evolution just grabs whatever signals are handy for a purpose, it doesn't have to make the kind of sense we would expect from a process we designed.

    The key insight is that we simply have not understood a very common aspect of immune response and recovery from exercise. This will not be the end of the story.

    Added: if T-cells are appearing in muscle tissues, where nobody expected them, they must be disappearing from peripheral blood. This might mean common tests would show a decrease in circulating T-cells.
     
    Last edited: Feb 9, 2016
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  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Not a lot. There are no T cell mediated autoimmune events in RA that I have ever heard of.
     
  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I think there is probably a simple misunderstanding underlying this stuff. We have seen T cells in muscle for decades. And that is no surprise because T cells have adhesion receptors that pick up changes in inflamed blood vessels. Just like neutrophils and macrophages they go to anywhere feeling poorly to check out what is wrong. I cannot see any reason to think t cell memory has anything to do with the training of muscle - which is something that has been studied in relation to T cell influx since I started in the Department of Medicine at UCL in 1982. If the authors think T cells cause rheumatoid arthritis they are clearly not up on the subject of T cell misbehaviour.
     
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  9. anciendaze

    anciendaze Senior Member

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    Rheumatoid arthritis is a kind of trainwreck, and based on an actual trainwreck I have seen I would expect the cause to be some distance from the big pile of wreckage. It is also a chronic disease and the theories of causation taught in medical schools get downright mystical when they have to deal with systems of feedback required to sustain a long-term pathological process. When I talk about dynamical systems with attractors, or even basic differential equations, I get responses indicating this has nothing to do with medicine. Ignoring dynamics in situations where you are clearly dealing with very complicated dynamical systems looks like a great way to remain ignorant.

    This is a special problem when clinical access to biological data is largely restricted to convenient physiological compartments. Without some way of inferring activity you can't directly access you are likely to be badly misled by the data you can easily obtain.

    I would also like to see some evidence of successful predictions. Explaining things after the fact can become little more than word games.

    I have no special brief concerning RA, but I am simply not impressed with the level of understanding which has persisted for the last 50 years. It is still listed as "of unknown etiology" and treatment options have not changed nearly as much as one might hope. A relative who was part of a research study was given high doses of methotrexate, and had enough liver damage to change color. At the time there was absolutely no doubt about the dangers of methotrexate. If such a study was still considered ethical in 1999 there must have been a real problem in the RA research community.

    I will admit I am exploring "long-shots" which have generally been rejected, but I think the long-standing lack of success points to a need for changes in thinking. If what you are doing is not working, you probably need to do something else.
     
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  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Try reading Edwards and Cambridge 1998 BJ Rheumatol. (specific prediction made) and then Edwards et al 2004 (proved right).

    I am not surprised that you are not impressed by the level of understanding that has persisted for 50 Years. That is just the literature generated by the dimbos who don't get it. 'Unknown aetiology' is a joke. But treatment options have changed out of all recognition - going from steroids and gold injections to TNF and IL-6 inhibitors and rituximab. I am not quite sure how much more radical a change you are looking for?? (Methotrexate always seemed to me a waste of space.)

    I think maybe you are a bit behind the times anciendaze!! When I started rheumatology in 1973 none of my patients had their disease course changed by treatment. When I left in 2010 there were very few patients whose disease was not controlled.
     
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  11. Sasha

    Sasha Fine, thank you

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    I'm maybe a bit OT but I think someone suggested on another thread that a patient only gets so many "goes" with rtx before it wears off so it couldn't be a long-term solution for PWME.

    Is that true (for RA)?
     
  12. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    That is more of a hypothetical worry than something established, Sasha. A few people have to stop riuximab but not usually because it wears off, more to do with low Ig levels.
     
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  13. Sasha

    Sasha Fine, thank you

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    That's a relief! Thank you. :)
     
  14. BurnA

    BurnA Senior Member

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    It just shows you what can be done, when there is enough money and interest in solving a problem.
    I guess the big difference is that you didn't have to convince people that RA was real ?
     
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  15. anciendaze

    anciendaze Senior Member

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    I'll check...
    What I consider real progress would be changes that reduce incidence. If the goal is to provide steady employment for doctors and reliable income for pharmaceutical companies the current situation is ideal. I am also aware of people who are seriously messed up as a result of either the disease or previous treatment. (I'm dealing right now with a relative who is in constant pain.) The sure way to avoid the disease is to die before onset, the only way to be free of disease after onset is to drop dead. This strikes me as highly unsatisfactory.

    Of course there is always the problem of patients who can't afford sophisticated treatment options, and various gatekeepers who limit access. I have in mind a friend who has been living with hepatitis C, apparently since a transfusion in 1968. Fortunately her husband has excellent insurance and can afford the copay of $5,000 on a $32,000 bill for 28 pills for the first month of three months of treatment. Total costs over $90,000 are typical. Unless incidence of HCV infection, etc. drops, that kind of cost will break any medical insurance system, public or private. I have similar unpopular opinions about heart bypass operations. This is a primitive medical intervention that shows we are far from understanding causes. The number of people who are not exactly healthy and not exactly dead continues to increase. No matter how we pay for it, I see us approaching a series of crises as recurring costs mount. I have no doubt the wealthy and well-connected will have a considerably different medical experience than the poor or politically weak.

    We now have to take careful legal steps to make sure we will not be maintained in a state just short of death that resembles medieval ideas of torture. I came to terms with fear of death itself in the military, but can't shake fear of some things I see regularly. Simply delaying death is not the ultimate goal. I would rather have people read that I died an untimely death at 100 in a freak skydiving accident.
     
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  16. lansbergen

    lansbergen Senior Member

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    It should not be but that is all I see happen.
     
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  17. anciendaze

    anciendaze Senior Member

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    This is partly because we have very limited understanding of what we are doing, so don't make interventions until the situation is life-threatening. There is some wisdom in that, but the real solution is to gain understanding so that other options make sense.

    I don't want to hijack this thread for a personal dispute with Dr. Edwards, particularly since it is not he himself who is the target of my ire. If I had a condition where he had direct professional experience I would probably be glad to have his advice as a practical matter. What bothers me is the belief that current understanding is acceptable, with only some small details to fill in. From personal experience I know that professionals operating with defective models of what they are doing can kill people, and I'm not demonizing the medical profession, I learned this in a very different context. I also have strong reason to believe current models are seriously defective, to the extent of omitting a wide range of fundamental questions. There are large professional blind spots in things I've mentioned like dynamic variation and signalling. There is now a substantial literature on biological signalling, dynamics and system theory, but this scarcely has any impact on the practice of medicine, and little impact on medical research. I keep seeing the same obviously defective models in publications, reviews and textbooks. A surprising number of professionals actually believe them.

    The progress he cites on the practice of treating RA is real, but deserves more scrutiny. About half the change has come by eliminating practices that were harmful. Positive changes have been introduced at about the rate of one per decade. Current best practice still fails one of my tests because it does not scale. This is not something that medical professionals are likely to think about per se.

    Experience with the transition from propeller-driven aircraft to spacecraft, or from vacuum tubes (valves) to VLSI, gives me a different perspective, and that is only the hardware. In my own lifetime I have recapitulated essentially the entire history of computation.

    Understanding of information as a Ding an sich has been more important than the touted changes in hardware. I have repeatedly seen ideas reimplemented using new means of fabrication. (Changes in implementation have come so fast that we have largely given up on introducing new acronyms like ULSI or MOSFET. They don't last long enough to catch on before they are superseded.) Medicine has recently received more solid information than was previously available in the entire history of the subject. So far, there is little idea what to do with this.

    We tend to think that we can go on the way we have been forever. We forget the cumulative effect of changes already in progress. Video and the Internet now mean we live in glass houses, compared to past civilizations. We tend to forget that more people are looking in than out. The current refugee crisis is an example of the problem of extending our comfortable bubble to accommodate others. Even small expansions involve crises. We are still arguing about how to pay for the last expansion.

    If we don't deal with the problem of scaling medicine and some other important aspects of convenient modern life in this century it is very likely the civilization we have built will be torn apart. I don't like the idea of a comfortable elite living in well-fortified castles as a future. Nor is bringing everyone down to a common level of misery attractive. We've already been there and done that, about 1,000 years ago.

    (Do you suspect I've been reading about the condition of "jolly old England" leading up to 1066?)
     
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  18. lansbergen

    lansbergen Senior Member

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    @anciendaze Do you know where I can find information of the innate response near basal membranes? I can not find what I want to know.
     
  19. anciendaze

    anciendaze Senior Member

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    One hell of a lot goes on "near basal membranes", and I'm not at all sure what you are looking for in terms of innate immune response. Are you talking about ion channels or transporter molecules as targets of immune activity, or is it something else entirely? The query may be too broad, and I'm probably the wrong person to ask. Try some specific instances which might lead you to more standard professional terminology.
     
  20. lansbergen

    lansbergen Senior Member

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    :Looking for how the local environment responses to infection near the basement membranes. There are many immune cells there but I can not find specific information about the innate response.

    The symptons occur to soon for antibodies and there is no known antiboy or other adaptive response to the infection I am after.
     

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