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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.
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Thanks, @SDSue@Simon Thanks so much for all the work you do getting information to PR members.
I wonder if you could point me to the part of the course, or your writings, that covers cytokines.
I have found a local osteopath who is having success with targeted treatment via cytokine nasal sprays. As you are likely aware, cytokines are currently being tested for use as adjuvants in nasal spray vaccines because of their profound affect on the immune system, and I could sure use a profound effect on my immune system! Because of all this, I'm very interested in learning more and possibly seeing this doctor.
Thanks again for all your work.
Thanks for the nice summary. I have a feeling Ian Lipkin has a greater mind than all of us put together, so the warning is duly noted!In one of his talks Ian Lipkin said that if the IL-17 finding in ME/CFS patients held up it might eventually be a therapeutic target eg using anti-IL17 antibodies - but he cautioned that it's too early to start testing, and warned that mucking around with cytokines can cause all kinds of problems. Cytokines are not necessarily your friend.
Thanks for these superb summaries, Simon. I try to read them when I have the energy, although that seems increasingly rare as Christmas approaches...
Nevertheless, when I read them, I am always impressed by the clarity of thought and expression you bring to this topic. I like your analogies too! keep it up - I hope you are getting a lot out of this course.
Thanks for the encouragment (especially pleased you like the analogies, @Battery Muncher), and thanks for sticking with this. As I'm learning in this course, the immune system is staggeringly complex and not easy to grasp.Back to school! That was brilliant - thanks Simon!
@Simon and others
I have some questions with regards to the development of autoimmune conditions and I'm hoping this is the most appropriate thread to ask..
So for a B-cell to become activated, it must first present to an (autoreactive) T-helper cell before it has a chance to start producing antibodies. What are the chances of this happening, given the tight selection processes of T-cells?
There is no requirement for these to come from the same molecule and in many cases they cannot (for antibodies to carbohydrates or DNA for instance). The system is set up so that they are likely to come from the same molecule because the B cell normally presents a peptide chopped up from an antigen it has ingested becuase it bound to surface antibody. But if the surface antibody binds to molecule A and molecule A is stuck to molecule B then the B cell will ingest and present molecule B as well. This has been understood as the most plausible explanation for a lot of autoantibody production since the early 1990s.
This is interesting, do we have any direct observational evidence that this happens?
The example of the gliadin-transglutaminase is a compelling one. Are there any other key parings like this?
How stable does this binding have to be?
Is it plausible for a B-cell to become active towards say, a kinase which was in the process of phopsphorylating a viral peptide? Or does this process happen too quickly for a B-Cell to ingest them at the same time? (or dephosphorylation or ubiquitination for that matter)
I think the idea you suggest about producing an antibody to a kinase that binds a virus is very much in line with what seems to happen in this model. The only reservation I would have is that phosphorylation of viral protein is likely to occur inside a cell and unless the kinase-protein complex gets released into tissue fluid where it can interact with B cell surface receptors it would not engage a B cell response.
FRIENDS, an old friend is manipulating the immune system
December 27, 2013 by SCIENCE ME
https://moms4science.wordpress.com/...old-friend-is-manipulating-the-immune-system/
Extract....
Summary
All four studies found an increased percentage of Tregs in patients diagnosed with ME/CFS. Regulatory T cells play an important role in maintaining immune homeostasis. Increased levels of Tregs have been found in many cancers and various chronic infectious diseases. Tregs are known to suppress other immune cells. The bystander immune suppression caused by increased percentage of Tregs could lead to reactivation of latent herpes viruses and other opportunistic infections commonly found in immune compromised patients.
Furthermore, these results would suggest that the immune system of patients with ME is unable to clear a chronic infection.
The interesting possibility arises of virus induced autoimmunity though?
For example, there are known viral mechanisms that interfere with apoptotic signalling, particularly for viruses with large genomes such as EBV. For example, BHRF1 has been shown to be a BCL-2 homologue in B cells and kinases such as VRK2 have been shown to phosphorylate BHRF1. JNK also phosphorylates BCL-2 (which inactivates it), so I'm wondering about potential cross-reactivity there too.
This still happens within the cell though, but surely the possibility exists for B-Cell interaction after cell lysis?
Edit - on additional thinking, I realised such antibodies would still be mostly useless, except perhaps as a potential catalyst towards development of a B-Cell lymphoma...
Lastly, there is this interesting theoretical study on the specificity of human kinases for phosphorylating viral proteins:
http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0040694&representation=PDF
Lastly, is your opinion on activated B cells themselves expressing CD40L and thus providing a survival signal during germinal centre processes?