One thing that I don’t understand is what happens to the cells in which the mRNA enters. Do they die? Do they go haywire? How are the spike proteins getting out of them? And if the cells die, how many of them are going to be affected by one shot?
as soon as the cell expresses S protien the immune system may then tag it and take a sample then produce a great many antibodies for the price of a small number of cells death relative to the large number of antibodies
In other words, is there a worry of MRNA causing auto-immune reaction/disease due to those proteins getting expressed by host's own healthy cells?
the mRNA of concern will not modify your DNA sequence, the expression of the S protien occurs untill the mRNA is destroyed by the cell, or the cell itself is destroyed taken apart and compared to self antigens, the foriegn antigen is expressed by MHC cells and PresenteD in a context of this is a hostile thing [a wanted poster]
this all occurs in a system of interdependent cell types and thier interactions.
your question addresses the crux of immunology, and needs a lot more attention than would be constructive here.
put on your reading cap and check this out:
keep in mind this is not proven but is a promising angle, CRSPR as made popular is a hijacked mechanism used to edit DNA sequences. normally this mechanism is used in prokaryotic organisms as an immune system. there are tags in the prokaryotes DNA that are used to match with foriegn DNA and signal it for destruction.
this type of arrangement MAY, possibly exist in eukaryotes as well and may be the basis of self/nonself recognition.
i have yet to talk to anyone else in professional context, this is inference on my part but it the best answer i can suggest for now.
you would want to look at antigen presentation and antibody production mechanisms, in deep detail .
Disclaimer: All I know about this comes from Cells at Work/Hataraku Saibou.
So if I understand you correctly, the self-recognition system is something built-in and doesn't change in response to foreign antigens? Or in other words, it's only the recognition of foreign molecules that will change, but this shouldn't affect the production (or culling) of T-cells that are super-sensitive to host's own self-antigens?
PS. And thank you and thanks to others for answering newbie questions on this thread! :)
I think the medical guidance has been pretty clear that you should not get the vaccine in this case. There are a lot of people who care more about their own safety than yours who may try to change your mind. Don't listen to them; don't get your medical advice on the internet. Find an expert.
the molecular level of the mechanism, beyond the cellular level is detail that needs to be elucidated.
> So if I understand you correctly, the self-recognition system is something built-in
Yes. before immune cells are released and "primed" they go through a selection process where the receptors they have for (unknown) antigens are tested against a vast array of proteins the body normally produces, if they bind, they are killed off. Sometimes this doesn't work and if they are activated and bind their (self-)antigen when the immune system is activated (i.e. during an infection) they can attack uninfected cells. Which as a one off event is not problematic, the problem comes from the fact that those immune cells stick around when they contact their antigen, and if it is produced by the body this is a lot, and continue to kill healthy cells and cause inflammation.
> and doesn't change in response to foreign antigens?
By the time the immune cells bind to foreign agents they have already gone through the selection process.
Necessarily a vaccine will produce an immune response (or otherwise it won't have the intended effect), this could cause an autoimmune response because the atuoresponsive cells, presumably, have their antigen around.
> but this shouldn't affect the production (or culling) of T-cells that are super-sensitive to host's own self-antigens?
new ones, no. In fact if you're not a child, you aren't producing many new (unique) T-cells at all. Old ones however may proliferate if their antigen is present and an immune response is triggered (to the vaccine or the virus).
If you want real advice, don't take it from some random on the internet with only a minor in biomed, talk to your doctor or immunologist.
Firstly they only express it as long as the mRNA remains intact. mRNA are degraded naturally so there is a finite time window as the mRNA is not reverse transcribed into DNA and reintegrated into the genome.
> what are the chances that it will also learn to react to other proteins expressed by those cells,
T (and B cells? I can't remember) cells undergo a selection process in the thymus that select against cells with receptors that bind to self proteins, that is proteins made normally by the body. Sometimes this fails and you get autoimmune disorders. Chances are very slim and no more than any other antiviral vaccine.
Why not? Just because it doesn't match up, or is there a deeper reason?
eukaryotes use splicing mechanisms that copy/delete/replicate DNA from one locus to another, this is more reliable as mRNA are unstable and become damaged quickly. cytoplasmic mRNA is not of fidelity and does not reverse compile into the dna sourcecode, or it would produce massive errors and corrupt the DNA.
Reverse transcription only happens when a reverse transcriptase (found in retro-viruses, e.g. HIV-1, HIV-2, Hepatitis B Virus etc) does that and the RNA is the direct viral genome or a transcript of the viral DNA (for DNA viruses). They have special marker sequences at either end to facilitate this (search for terminal repeats)
SARS-CoV-2 is not a retrovirus.
The CDC and other sources argue the vaccine is safe because it doesn't alter your DNA, but I have a vivid imagination and can think of a thousand other ways something might go wrong. Having my DNA altered was never one of my concerns.
what you would get is some false starts, and segment of protien if that at all.
https://en.wikipedia.org/wiki/MHC_class_I#Effect_of_viruses
I don't honestly understand how the immune system decides which protein fragments are okay to develop a response to, but the point is that that is already part of the normal immune response pathway that learns new antigens every day; after the protein fragment shows up on the cell surface, the rest of the process is similar to the response to an attenuated-virus vaccine or a natural infection.
keep in mind there is no proof yet that this is how it works but it is a promissing direction to look into.
I'm no expert either, but I don't see a difference here between virus infected cells and mRNA "infected" cells. So cells primed with mRNA simply produce less virus parts than those with the real virus?
the vaccine is not the whole mRNA, its only the part that codes for immunogenic protien [SARS-2 S] that is exported to the cell membrane
this is not a constituative expression and the cell expressing the foriegn protien is often destroyed later in the process but not always as the vaccine mRNA is edited out of the cytoplasm not replaced by genetic expression and the novel protien goes into turnover mode.
...no? This is not gene therapy. The effects of receiving a mRNA vaccine will, apart from training the immune system (which was the whole point), be next to nothing.
Your body is continually being bombarded with random foreign DNA and RNA. That's just how life on Earth works. Yes, introducing a big pile of it at once is not normal... but it's a difference of degree, not something completely new.
If anything, problems are more likely to derive from the lipid bubbles used (at least by Moderna) to package and transport the mRNA.
Noob here, could you expand on that?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583697/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624045/
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edit: Here is more specific information on lipid nanoparticles in RNA vaccines, which explains that RNA vaccines that involve lipid nanoparticles tend to cause a local inflammatory effect, i.e. shoulder soreness.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963972/#sec3-v...
It is absolutely not anything like merging a patch into the master branch.
There are also other delivery pathways for mRNA vaccines.
The virus is not functional because the mRNA vaccine only contains one little component of the virus, the spike protein.
You can see a quick comparison chart of the most important vaccine methods in this Nature figure: https://media.springernature.com/lw685/springer-static/image...