Salugenesis and the Cell Danger Response: Dr. Robert Naviaux

[leokitten]

Well I really do hope Davis, Naviaux, or Prusty do finally prove or disprove that it’s something systemic with immune system and cellular energy mechanisms.

We all want to know if ME is purely a neurological disorder (inflammation, energy dysfunction only in brain, infection in brain) causing effect on organs, the full body feeling of energy depletion and all the other symptoms, or if it’s systemic via immune and cellular energy dysfunction and signaling affecting brain and other organs.

At my stage in the disease (8 years) those very strong symptoms of chronic immune activation have reduced from the early years and it mostly feels like all of that just damaged my CNS and the symptoms are mostly coming from CNS dysfunction.

 

[Rufous McKinney]

The combination of a dysregulated system that is energy depleted (with minimal capacity if any to rebound) and at the same time in a super vigilant state of protection.

I am seeing this much more clearly recently, in terms of my IBS symptoms. I've been in a highly depleted state for almost two years. I'm finally getting the level of absolute rest required to improve a bit. Suddenly my gut is functioning way better and its not probiotics, its not avoiding suspicious foods. I seem to have a bit more energy and now my gut can better defend itself.

So for years now, I can tell how much energy the brain takes. Its huge. When you have insomnia, and lists going...and your ravenous and its 4 am.

I also face really abrupt losses of energy. And then the brain goes almost blank. It ceases holding thoughts and information in a connected way. Holding that thought: costs energy.

 

[Rufous McKinney]

Literally the Elephant in the Room! We get caught up in all of the Metabolic, Viral, Stress and Functional features of ME/CFS that it is easy to forget it is all about energy first and protection second

Just now i felt like asking the Computer Gods- whats with ATP and red blood cells (thinking about those)...and kaboom the laptop says this:

"Most of the ATP is used to maintain the ion balance, cell volume, and RBC deformability."

So Stanford and Davis found its likely we have non-deforming red blood cells. So right there, we have an opportunity for a simple- ran out of ATP, can't deform -relationship. Then its likely they aren't delivering the oxygen well to the end organs through the narrowest capillaries.

So every single task the body takes up will have to include an energetic cost.

 

[Pyrrhus]

it is understood now that T cells do cross over the BBB when signaled that they are needed.

Possibly relevant: A relatively recent discovery is the discovery of Tissue-resident Memory T cells, abbreviated Trm. These are memory T cells that live inside organs, such as the brain, and are distinct from blood-borne T cells:
https://immunology.sciencemag.org/content/4/34/eaas9673

 

[leokitten]

I am seeing this much more clearly recently, in terms of my IBS symptoms. I've been in a highly depleted state for almost two years. I'm finally getting the level of absolute rest required to improve a bit. Suddenly my gut is functioning way better and its not probiotics, its not avoiding suspicious foods. I seem to have a bit more energy and now my gut can better defend itself.

So for years now, I can tell how much energy the brain takes. Its huge. When you have insomnia, and lists going...and your ravenous and its 4 am.

Probiotics actually made my ME gut issues worse. No matter what exotic probiotic or not that was mentioned here on PR or others, they all caused me to have increased gut issues and made me worse. Moment I stopped it got better. I honestly feel for most of us there isn’t any real microbiome issue, it’s that our immune system is in chronic activation mode and guess what 70% of immune system is in and around the gut, so my immune system just further activated when a bunch of new probiotic bacteria got down there making symptoms worse.

Btw wow do you get this increased hunger particularly after overexertion and it becomes ravenous when you’ve overdone it so much you are headed for a crash? There are a few of us here that have this symptom. For me it didn’t start until around 3-4 years into the illness, basically at some point as my severity had slowly gotten worse.

 

[Rufous McKinney]

No matter what exotic probiotic or not that was mentioned here on PR or others, they all caused me to have increased gut issues and made me worse.

I don't take probiotics very often and have in fact had adverse results at times from them. My chinese traditional medicine doctor also does not trust them. I also don't think I am getting alot of probiotics in foods I eat- I tend to eat cooked food and not much raw.

I do have some erratic blood sugar- am trying to avoid going type 2. I seem to be much better- now generally with the blood sugar. But I do tend to eat small amounts frequently, have sudden abrupt drops and have to eat right now type of thing. But its quite a bit better than it was. I can be- at times ravenous for- protein.

 

[Wishful]

The Trm cells certainly add complications. They aren't understood very well yet, so it's certainly possible that they play a role in ME. What if there are Trm cells restricted to specific parts of the brain? Kind of hard to spot specific t cells in the brain. They may use signals that aren't looked for, since they're not used by regular t cells.

Here's a scenario: an immune activating event occurs somewhere in the body. That sends some signals that reach some Trm cells in the brain, causing them to activate, and affect other cells in some way that in turn keeps the Trm cells active. Exactly where these Trm cells are activated, and how they respond and how other cells respond varies with the individual, creating the myriad of symptoms and responses we see with ME. Occasionally, some chemical might manage to switch these Trm cells back into the normal state, giving an abrupt switch out of the ME state, but the system somehow adapts to switch us back into ME. Is this something present medical technology can detect if actively looked for?

 

[Pyrrhus]

Possibly relevant: A relatively recent discovery is the discovery of Tissue-resident Memory T cells, abbreviated Trm. These are memory T cells that live inside organs, such as the brain, and are distinct from blood-borne T cells:
https://immunology.sciencemag.org/content/4/34/eaas9673

The Trm cells certainly add complications. They aren't understood very well yet, so it's certainly possible that they play a role in ME. What if there are Trm cells restricted to specific parts of the brain? Kind of hard to spot specific t cells in the brain. They may use signals that aren't looked for, since they're not used by regular t cells.

Yes, it's certainly possible that tissue-resident memory T cells (Trm) may play a role in ME. We just don't know much about them yet...