Phage , the virus that cures

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Hi Gibson, i read something interesting that may have a strong implication on how to handle in the future autoimmune diseases.
As it turns out, the inoculation against measels may have prevented humanity from overlooking a perhaps ancient practice which we now only see in the movies as magic but is just a very smart trick of healing in sequence and that the enemy of my enemy is my friend for a moment : The measels.
As it turns out, by accident Dutch researchers and English researchers sort of stumbled on something in the dutch biblebelt where measle vaccination does not occur.
The children had a very weird symptom after healing from the measles infection. They lost there memory cells for previously encoutered diseases. And that may be interesting to counter auto immune diseases acquired through molecular mimicry.

The dutch Amsterdam UMC and Wellcome Sanger Institute in Cambridge is researching it since 2019. It is in dutch, so you have to translate.

"
Not only do people get sick from measles, the virus also has a major impact on the immune system of patients. This increases the chance of another illness after the children have measles. Researchers from Amsterdam UMC and the Wellcome Sanger Institute in Cambridge have mapped out how the measles virus paralyzes the immune system. They will publish Thursday in Science Immunology.
"

Why do i come up with ancient practice that we only see in movies ?
Well, let's think of the following scenario : Sometimes sick people where brought to a healer. The healer gave them something, a potion that fights the disease but the potion also will kill them. So after killing the disease, the potion must be neutralized...

Perhaps many diseases can be cured that way as when i was talking with my friend in the gym ,we talked about how certain parasites fight of other parasites...

What is your take on it ?
 
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Look, more mounting evidence what the cause is of multiple sclerosis.


It is now a question to why it happens.
Here is a postulation :
There may a way : What i read, is that with some people the EBV virus seems to hide in sleeping memory b cells.
What if something happens to such a cell that it reactivates and starts pumping out antibodies that lock on to the proteins of the myelin sheet of the nerve fibers ?
What if it is a coinfection ? 2 virus infections at once ? The EBV virus is inside a resting memory b cell. Then an RNA virus infects the cell which also has some trick up it's sleeve similar to reverse transcriptase. Somewhere inside the b memory cell, antibodies are created as explained in a simple way here :


A coinfection inside an infected memory b-cell might be the cause of multiple sclerosis.

The big questions are : Is there a protein on the EBV virus that looks similar like for example myelin basic protein ? And is it molecular mimicry ?
Or is there just something weird going on in the antibody production department inside the (EBV) infected memory b cell ?

EBV = Epstein Barr Virus = Human herpes virus 4 [HHV-4]
Also, EBV is known for mono AKA kissings diseases AKA (ziekte van Pfeiffer).
 
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Gibsons

Lifer
Aug 14, 2001
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So let's see -
I personally have zero concerns about Sarscov2 integrating in the human genome. For me or humanity in general.

EBV causing MS - three possible mechanisms are:
1 antigen mimicry - Abs against various EBV proteins cross react to self proteins. there are documented examples of this.
2 EBV causes or allows B cells to migrate to CNS, causing inflammation from there. We know the migration happens, whether that's necessary for MS to develop, who knows.
3 immortalized/infected B cells are less subject to control or anti inflammatory mechanisms. Kind of hand waving here, but EBV does immortalize B cells.

These could all be working together, they aren't mutually exclusive. And of course there are almost certainly things going on that we don't know about or even suspect.

This was a huge, important discovery imo. Pinning down causes of autoimmunity has been problematic.
 
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May 11, 2008
18,325
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So let's see -
I personally have zero concerns about Sarscov2 integrating in the human genome. For me or humanity in general.

EBV causing MS - three possible mechanisms are:
1 antigen mimicry - Abs against various EBV proteins cross react to self proteins. there are documented examples of this.
2 EBV causes or allows B cells to migrate to CNS, causing inflammation from there. We know the migration happens, whether that's necessary for MS to develop, who knows.
3 immortalized/infected B cells are less subject to control or anti inflammatory mechanisms. Kind of hand waving here, but EBV does immortalize B cells.

These could all be working together, they aren't mutually exclusive. And of course there are almost certainly things going on that we don't know about or even suspect.

This was a huge, important discovery imo. Pinning down causes of autoimmunity has been problematic.
Thank you, Gibson. That is fascinating. Encouraging the curiosity indeed.

2 EBV causes or allows B cells to migrate to CNS, causing inflammation from there. We know the migration happens, whether that's necessary for MS to develop, who knows.

Now this, Gibson. Is a very improtant clue. What mechanism lies beneath this systematic migration to the CNS ?
How does the migration occur ? Is it just jump in the bloodstream and hope to get there by chance ? Or is it really like an encoded map of the body. To know how to get there and that the EBV hijacks this ?


3 immortalized/infected B cells are less subject to control or anti inflammatory mechanisms. Kind of hand waving here, but EBV does immortalize B cells.

immortalized b cells. I have never heard of that description before. That is like a precursor to a tumor cell ? Yes ?
 

Gibsons

Lifer
Aug 14, 2001
12,528
30
91
Looks like I misremembered a bit about B cells migrating to the brain. They can and do migrate to the brain (so can T cells and other immune cells), it's definitely seen in MS, and thought to be a contributing factor towards disease. It's due to expression of an integrin that allows them to cross the blood brain barrier (there are other ways iirc). But... I'm not sure where I got that EBV actually causes the integrin expression and subsequent migration. I can't find a reference for it. :( I guess it's possible that it does, but it's just supposition.

immortalization (disclaimer: over-generalizations incoming)

So, cancer 101. If you take a 'normal' cell (good luck defining that, I won't try) from a human and put it in a culture flask, feed and talk to it real nice, it will grow. It will sick to the bottom and divide until it covers the bottom surface of the flask in a single cell layer, then stop. If you take a cell(s) from that, and put it in a new flask, it grows and covers the new flask. Keep repeating this and eventually, the cells stop dividing. How often they divide depends on a few things, but a typical number of divisions might be 50 (called the Hayflick limit). That's a 'mortal' cell, it has a finite ability to divide.

On the other hand, take cancer cells, and they will usually (not always, CLL being a maddening exception for me personally) divide as long as you care to keep dividing and feeding them. That's an immortal cell line, it has an apparently infinite capacity to divide. Most or all of the difference is due to telomerase.

Side note, the cancer cells will also grow on top of each other in piles, compared to the single layer of normal cells. The terms here are 'contact inhibition,' (they grow in a single layer, stop when they contact another cell) and 'transformation' (basically a loss of contact inhibition). So, most cancer cells are usually transformed and immortal.

One reason EBV has been so well studied for so long is that it immortalizes B cells. So in the early days when B cells were starting to get picked apart and we knew almost nothing about telomerase, you could take a B cell from any old source (not really), infect it with EBV, and grow up as many as you cared to. A question that still isn't quite answered: if immortalization is about half of what you need for cancer, why doesn't EBV cause tons of B cell cancers? It's definitely causative in the endemic form of Burkitt's lymphoma, but not much else.
 
May 11, 2008
18,325
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Looks like I misremembered a bit about B cells migrating to the brain. They can and do migrate to the brain (so can T cells and other immune cells), it's definitely seen in MS, and thought to be a contributing factor towards disease. It's due to expression of an integrin that allows them to cross the blood brain barrier (there are other ways iirc). But... I'm not sure where I got that EBV actually causes the integrin expression and subsequent migration. I can't find a reference for it. :( I guess it's possible that it does, but it's just supposition.

immortalization (disclaimer: over-generalizations incoming)

So, cancer 101. If you take a 'normal' cell (good luck defining that, I won't try) from a human and put it in a culture flask, feed and talk to it real nice, it will grow. It will sick to the bottom and divide until it covers the bottom surface of the flask in a single cell layer, then stop. If you take a cell(s) from that, and put it in a new flask, it grows and covers the new flask. Keep repeating this and eventually, the cells stop dividing. How often they divide depends on a few things, but a typical number of divisions might be 50 (called the Hayflick limit). That's a 'mortal' cell, it has a finite ability to divide.

On the other hand, take cancer cells, and they will usually (not always, CLL being a maddening exception for me personally) divide as long as you care to keep dividing and feeding them. That's an immortal cell line, it has an apparently infinite capacity to divide. Most or all of the difference is due to telomerase.

Side note, the cancer cells will also grow on top of each other in piles, compared to the single layer of normal cells. The terms here are 'contact inhibition,' (they grow in a single layer, stop when they contact another cell) and 'transformation' (basically a loss of contact inhibition). So, most cancer cells are usually transformed and immortal.

One reason EBV has been so well studied for so long is that it immortalizes B cells. So in the early days when B cells were starting to get picked apart and we knew almost nothing about telomerase, you could take a B cell from any old source (not really), infect it with EBV, and grow up as many as you cared to. A question that still isn't quite answered: if immortalization is about half of what you need for cancer, why doesn't EBV cause tons of B cell cancers? It's definitely causative in the endemic form of Burkitt's lymphoma, but not much else.
Integrins. That is interesting. I have to read about that.

Cancer 101. Indeed. I know a little bit of something about that. Telomeres. the regeneration of telomeres. Telomeres also being used as a sort end of sentence instruction when DNA is being read. I purchased this book (see picture) about Henrietta Lacks last year but have not read it yet about the immortal HeLa cells and how aggressive they are. They even grow inside the body of another human and likely also in other mammals a while before the immunesystem will succesfully remove the HelA cells after time. But that starts to sound like transmittable cancers like some Canine versions and Tasmanian devils versions after biting eachother and passing on the cancer cells through open wounds and blood... Some really nazi alike illegal experiments were done using inmates in a prison in the USA. Weird fact is that the HeLa cells came to existence after a uterine cell became infected with HPV-18 and syphilis and got a large amount of chromosomes around 78 of them. She was the poor victim of infidelity from her husband. If only he kept his pecker inside the pants...

That contact inhibition and transformation is interesting. I read somethings about tumors. And it seems that the aggressive ones were comprised of cells that were able to differentiate into cells with specific functions. Like a new organism. Some were more optimized for replication, others were very good at pumping out all kinds of signal molecules for the body to start generating new bloodvessels for the tumor to feed upon to be able to grow faster because of getting more nutrients than the surrounding tissues. A fact used by the current chemical therapies.

Hayflick limit. There are some animals where there is something weird going on with the hayflick limit. But i forgot the animal.
I never knew about normall cells only wanting to grow in 2 dimensions in a flask.

This is also an interesting TED talk by Nobel prize winner Elizabeth Blackburn, about the increased shortening of telomeres because of chronic stress.

And i found this useful a while ago , for you Gibson, it is easy material but for us microbiology amateurs and peasants very handy :tearsofjoy:: https://www.yourgenome.org/facts/what-is-a-telomere

What makes me kind of mad, is that it is known for so long how dangerous EBV is and no one ever bothered to make a vaccine for it before but i guess it was very difficult to impossible create a save one.
They always say it is a perfectly harmless virus while it is obvious it is not. Immortalizes B cells swimming around in the body does not sound very comforting.
I learned that moderna is busy with a trial to start with a EBV vaccine based on the same technique now used for SARS-CoV2 virus : mRNA vaccine.


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The venereal disease gonorrhea is again spreading enormously and is now also quite resistant to most antibiotics. Gonorrhea is a disease that develops after infection with the bacterium Neisseria gonorrhoeae through sexual contact. In now not so rare cases, the bacteria can also spread to other parts of the body. Also to the brain and thus cause ultimate psychological complaints due to local infections in the brain. And also cause meningitis. Another example is that inflammation of the heart valves can also develop, which can even become chronic, increasing the risk of heart failure. Just to name a few examples.


"
An existing vaccine that prevents meningococcal disease may also be up to 40 percent effective at preventing gonorrhea infections, which are becoming increasingly resistant to antibiotics, with some strains completely incurable. This discovery is according to a series of studies and commentaries published Tuesday in The Lancet Infectious Diseases.
Though the estimated effectiveness is modest, shots of the vaccine—4CMenB aka Bexsero—could still prevent many infections, researchers reported. The vaccine could prevent more than 100,000 gonorrhea infections over 10 years in the UK, saving an estimated $10.4 million. In the meantime, the vaccine's effectiveness could provide significant clues for vaccine developers to make a more effective gonorrhea-specific shot.
The need for such a vaccine is clear. Not only is gonorrhea quickly becoming more drug-resistant, but it is also on the rise in the US and other countries. The World Health Organization estimates there were more than 82 million gonorrhea cases worldwide in 2020. The US Centers for Disease Control and Prevention estimates there were nearly 680,000 cases in the US in 2020, up 10 percent from 2019 and up 45 percent from 2016.

In a press conference Tuesday, Jonathan Mermin, director of the CDC's National Center for HIV, Viral Hepatitis, STD, and TB Prevention, highlighted the optimism around using 4CMenB to prevent gonorrhea. "There's more research going into that," Mermin noted, "but it does show at least some hope that in the future we could be developing effective and safe vaccines against gonorrhea, which would help us more successfully reverse some of the trends that we've been seeing over the past 10 years."
The effectiveness of a meningococcal vaccine against gonorrhea stems from the fact that the two diseases are caused by related bacteria—Neisseria meningitidis and Neisseria gonorrhoeae, respectively. Previous research has suggested that the vaccine could provide cross-reactive immune responses, given that the two microbes share significant amounts of their genetic code and key proteins targeted by the vaccines.

Multipurpose vaccine

In the series of studies published Tuesday, two were case-controlled observational studies looking at the real-world effectiveness of 4CMenB against gonorrhea infections in specific populations in the US and Australia.
In the US-based study, led by the CDC's Winston Abara, researchers used health records of gonorrhea cases in people ages 16 to 23 in New York City and Philadelphia from 2016 to 2018. The cases were matched to others in the same age group who had chlamydia—the control group.
The researchers had records of nearly 168,000 infections (approximately 18,000 gonorrhea infections, 125,000 chlamydia infections, and 25,000 co-infections) among almost 110,000 teens and young adults. Of those, nearly 7,700 were vaccinated with at least one dose—about 4,000 had one dose, and 3,600 had two doses. The researchers estimated that having two doses provided 40 percent protection against gonorrhea, and one dose was 26 percent effective.
In the second study, Australian researchers tapped into data on more than 53,000 teens and young adults who received one dose and 46,000 who received two doses in South Australia as part of a statewide program. Looking at the vaccination status of gonorrhea cases and using chlamydia cases as controls, the researchers estimated that the 4CMenB vaccine was 33 percent effective at preventing gonorrhea.
The studies have several limitations. For instance, the researchers cannot determine how long such protection may last against gonorrhea after vaccination. The studies looked at specific populations, so the estimates may not be generalizable. Still, any modest benefits could significantly impact disease spread, especially in high-risk groups, such as young adults and men who have sex with men (MSM).
In a third study released Tuesday, researchers in the UK modeled the cost-effectiveness of using the meningococcal vaccine 4CMenB to prevent gonorrhea infections. They estimated that vaccinating at-risk MSM could prevent 110,000 cases in the UK over the next 10 years, saving $10.4 million in testing and treatment costs. And those estimates are conservative. The researchers assumed that one dose of the vaccine does not provide any protection. The study also didn't account for extra costs that may be associated with drug-resistant gonorrhea infections.
"With a gonorrhea-specific vaccine likely to take years to develop, a key question for policymakers is whether the meningitis vaccine 4CMenB should be used against gonorrhea infection," lead author of the modeling study, Peter White, of Imperial College London, said in a statement. "Our analysis suggests that giving the vaccine to those at the greatest risk of infection is the most cost-effective way to avert large numbers of cases."

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