• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

What might remissions mean?

Jonathan Edwards

"Gibberish"
Messages
5,256
The gut mucosa are crucial to building and maintaining the immune system, are they not, @Jonathan Edwards? Could this be one key to fluctuations, including full-blown remissions and relapses, at least for some people?

This looks a rather interesting paper on the gut and immunity.

A lot of antibody is produced in the gut wall by plasma cells that lodge there but I am not sure about events in the gut being that important. My impression is that the gut is permanently full of all sorts of dreadful stuff and has a pretty good way of coping. I suspect that gut disturbances occur when the immune system is activated because antibody production revs up there as part of the response - rather than the other way around.
 

lansbergen

Senior Member
Messages
2,512
On the other hand if the B cells are suspicious and they convince the T cells this is an alien by spraying their luggage with a little cocaine then the T cells will start yapping and the B cells can kick them out even if in fact they are perfectly law abiding citizens.

How do Bcells convince failing Tcells?
 

trails

Senior Member
Messages
114
Location
New Hampshire
@Jonathan Edwards, thank you very much for the wonderful analogies you previously provided in this thread.

I understand that Rituximab is not being touted as a cure. However, I'm hoping you can tell me why, after undertaking the rtx protocol, one wouldn't assume that the body will rapidly return to a state of producing "bad" b-cells in response to a particular antigen thereby resulting in a relatively quick relapse. If you have already answered this question in a previous post(s), please feel free to point me in that direction.
 

lansbergen

Senior Member
Messages
2,512
self-perpetuating:Having the power to renew or perpetuate oneself or itself for an indefinite length of time.

I do not understand what that has to do with: How do Bcells convince failing Tcells?

I want to know how Bcells make failing Tcells to do their job again.



@lansbergen , Jonathans response in an earlier thread: :)

"The self-perpetuating signals are various and complicated and not very easy to explain in an internet post. The general idea and several examples were given in a paper I wrote with G Cambridge and V Abrahams in 1999. You shuld find it at
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2567.1999.00772.x/full"
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
I do not understand what that has to do with: How do Bcells convince failing Tcells?

I want to know how Bcells make failing Tcells to do their job again.

Jonathans theory is that B-cells are the culprit for autoimmunity, not T-cells. So in that respect, the link is only indirectly relevant..
 

ghosalb

Senior Member
Messages
136
Location
upstate NY
Absolutely cyclic and haphazard! A very good way to put it.

I need to be a bit more precise but there is an interesting subplot here. An intriguing aspect of the immune system is that it tends to work a bit like the cockpit of an airliner. Decisions are never given to one cell clone to make. There is always a co-pilot to make sure the pilot has not gone bonkers. Intriguingly, although the lymphocytes in sharks are quite different from ours they also have decisions made by two sorts of cells the way we have decisions made by T and B cells.

The basic co-pilot system for immune responses is that both B and T cells have to agree that an antigen is an alien. Autoimmunity sets in if the B cells shut the door when the T cells have gone to the loo - or perhaps a better analogy is that they fool the T cells into thinking they are attacking an alien when they are attacking self.

But even within the B cell system there is a beautifully designed co-pilot requirement. B cells expand by chain reaction when a microbe attacks because the more antibody is made the more the antigen can be passed around to new cells to stimulate more antibody. But the new cells obviously have to pick up the antigen by a different handle if they are being shown it by an antibody from the first cell attached to another handle. That has the interesting effect that a single B cell clone can never stimulate itself to make more antibody beyond a certain point. Once there is enough antibody to stick to all the handles on the antigen that B cell can see it cannot stimulate through further handles.

Forget worrying if it seems too complicated but the basic outcome is that autoantibody production has to come from at least two and more likely several B cells, each recognising a different handle on the same antigen.

Now B cell clones are in constant competition with each other and even if fairly successful, tend to die out and be replaced by other clones. So what seems likely to happen in autoimmune disease, and there is quite good evidence from tracking b cell clones in joints for instance, is that the collection of B cell clones causing the trouble is constantly changing. A bit like a tennis club, members come and go. But you always have at least two members to play tennis and even if the members have all changed the game is still tennis (making a certain autoantibody).

So that's a very long winded explanation for why we should expect autoimmune diseases to wax and wane all the time because the tennis club members are always changing and some are better at tennis than others. And so you get cycles of good and bad tennis and it is all haphazard because B cell generation is a random process!
Thank you Professor.....your students were very lucky.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
@Jonathan Edwards, thank you very much for the wonderful analogies you previously provided in this thread.

I understand that Rituximab is not being touted as a cure. However, I'm hoping you can tell me why, after undertaking the rtx protocol, one wouldn't assume that the body will rapidly return to a state of producing "bad" b-cells in response to a particular antigen thereby resulting in a relatively quick relapse. If you have already answered this question in a previous post(s), please feel free to point me in that direction.

Great question. It seems from phase 2 that some immune systems possibly get "cured" after rtx, while some stay longer in remission before "bad" b-cells recurr, and some unlucky patients get them back all the quicker..
 

ghosalb

Senior Member
Messages
136
Location
upstate NY
Thank you MeSci for starting this great thread.
This is my two cents.....
I understand that there are 3 types of CFS patients....1. those who get it at an early age and recover completely on their own..........2, those who get it, then improve, relapse, improve, relapse..... but each relapse/recovery is worse than the last one.......3. those who get it and never improve. I fall in group 2...this is my third recovery...but last relapse was so bad, I am afraid I may not make it during next relapse. Anyway, can autoimmune disease explain this ?
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I had a number of instant remissions back when I was on Immunocal. They typically lasted for six hours. I did not always immediately notice them, I just felt normal. Then I realized that it really was normal. During this period my overall health was higher than for most of the decade before, I had moved to mild ME.

On occasion I have taken advantage of this in absolute amazement. One time I went from struggling to walk to being able to run for miles. This improvement was there and gone in six hours. Another two times my brain immediately kicked in. Of those two, in one I was suddenly able to solve tutorial questions on physical chemistry involving math (I was at uni) in my head, that before I was struggling to do at all. On another occasion was right before an exam. My reading speed suddenly went from struggling to thousands of words a minute. I mean really really fast. That remission lasted long enough for me to finish the exam. On reflection most of these occurred during a natural rise in stress - good stress mostly, such as seeing a movie at the cinema.

To me this indicates there is not huge structural damage even at the molecular level for a subgroup of us. Its about dynamic regulation of something. However this does not rule out severe damage that the body can sometimes compensate for, but such compensation is not sustainable.

I use a wave analogy, and its only an analogy, reality is more complex. Think of the causes of symptoms as waves, which wax and wane. Waves go up and down. There are numerous such waves. Spontaneous crashes without triggers occur when a bunch of these waves peaks coincide and reinforce each other. However, when the troughs of the waves coincide the symptoms just go away. It might be rare, but it can happen.

In reality these waves are biochemical signals, They are however not constant. They will wax and wane with various biochemical factors, including regulating systems.

That leads me to at least two possibilities. Either some dynamic system, probably involving brain and hormones, is driving the symptoms. Or the same dynamic system is fighting the damage, and can sometimes overcome it on a temporary basis. Of course these two are not mutually exclusive.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
A lot of antibody is produced in the gut wall by plasma cells that lodge there but I am not sure about events in the gut being that important. My impression is that the gut is permanently full of all sorts of dreadful stuff and has a pretty good way of coping. I suspect that gut disturbances occur when the immune system is activated because antibody production revs up there as part of the response - rather than the other way around.

I'm rather surprised that you don't think that the gut is important in regulating the immune system, Prof Edwards, but at least you can't be accused of bandwagon-jumping, as there is a very big bandwagon at present about the gut microbiome and immunity! :D

I am one of those who has been very excited about these developments, and was very interested in this Phoenix Rising article.

This quote sums it up well for me:
More immune cells are in the gut than anywhere else in the body, which makes sense as that's where most bugs are too. But it isn't simply bugs and our immune system facing off against each other: it turns out that the immune system needs the microbiota both to develop normally and to keep to keep it on an even keel.

Any comments on that quote?

It is certainly in keeping with my own experience of many symptoms improving after I brought about an improvement in gut function. These have included weight normalisation, disappearance of dermatitis and sinus congestion and the mood and sleep improvements mentioned earlier but, like so many improvements, these have worsened again when my gut function deteriorates, for reasons which are not usually/always clear but probably include overexertion and dietary errors.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I do not understand what that has to do with: How do Bcells convince failing Tcells?

I want to know how Bcells make failing Tcells to do their job again.

There aren't any failing T cells as far as I am aware. I do not think we have any evidence for failing T cells in either ME or most autoimmune diseases. The B cells fool perfectly normal T cells by passing them fragments of foreign antigen that has been attached to self antigen and taken in by the B cell.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I am starting to think you mean something else than I think it means they left and the bcells prevent they come back in.
Can you explain what you mean?

That particular analogy was not very good, and maybe an inappropriate reference to terrorist episodes. The cocaine on the luggage was better - as I think I suggested.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Thank you MeSci for starting this great thread.
This is my two cents.....
I understand that there are 3 types of CFS patients....1. those who get it at an early age and recover completely on their own..........2, those who get it, then improve, relapse, improve, relapse..... but each relapse/recovery is worse than the last one.......3. those who get it and never improve. I fall in group 2...this is my third recovery...but last relapse was so bad, I am afraid I may not make it during next relapse. Anyway, can autoimmune disease explain this ?

Autoimmune diseases can follow all three patterns. The emphasis is different for different diseases. Type 1 is rare for RA - it is mostly type 2 or 3. Immune thrombocytopenia is quite often type 1. Lupus is mostly type 2 if you get sufficient treatment to survive severe episodes.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
Thank you MeSci for starting this great thread.
This is my two cents.....
I understand that there are 3 types of CFS patients....1. those who get it at an early age and recover completely on their own..........2, those who get it, then improve, relapse, improve, relapse..... but each relapse/recovery is worse than the last one.......3. those who get it and never improve. I fall in group 2...this is my third recovery...but last relapse was so bad, I am afraid I may not make it during next relapse. Anyway, can autoimmune disease explain this ?

I think there are more than 3 types, as does @Jonathan Edwards - see this thread.

I am not worse than I was at the start (20 years ago) except perhaps in terms of mental and physical energy. But then I am 20 years older! Sometimes mental and physical energy are good for a while - typically a few hours. I have had improvements, two which were near-remissions, but was not worse after these. Many symptoms have improved, some have worsened again, and many fluctuate, as they do with most of us. I was in my 40s when I became ill.

I think it's crucial not to risk over-exertion during remission, as that too-often leads to major relapse.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I'm rather surprised that you don't think that the gut is important in regulating the immune system, Prof Edwards, but at least you can't be accused of bandwagon-jumping, as there is a very big bandwagon at present about the gut microbiome and immunity! :D

I am one of those who has been very excited about these developments, and was very interested in this Phoenix Rising article.

This quote sums it up well for me:


Any comments on that quote?

It is certainly in keeping with my own experience of many symptoms improving after I brought about an improvement in gut function. These have included weight normalisation, disappearance of dermatitis and sinus congestion and the mood and sleep improvements mentioned earlier but, like so many improvements, these have worsened again when my gut function deteriorates, for reasons which are not usually/always clear but probably include overexertion and dietary errors.

When I see a bandwagon coming I let it pass. They go nowhere in general.

I think the idea that gut flora regulae our immune response is hype to be honest. It comes mostly from experiments with mice put in environments with no bacteria.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
There aren't any failing T cells as far as I am aware. I do not think we have any evidence for failing T cells in either ME or most autoimmune diseases. The B cells fool perfectly normal T cells by passing them fragments of foreign antigen that has been attached to self antigen and taken in by the B cell.

And that combination of antigen the "bad" b cells carry is obviously not due to a conscious decision, but however, a consequence of those b-cells` individual genetics?