6 ms·

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

by lrossi 6y ago

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?

rolph 6y ago
its a game of numbers and timing. first off there is a patrol inside that cell that cleans up mRNA that doesnt have a "hall pass" cells that are very damaged or confused will go into a procedural death mode called apoptosis, different from simple cell death as others are imformed of events and can react accordingly. 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
- rolph 6y ago
  addendum >>there is a halflife/turnover rate, in tech terms the hardware is updated very frequently, by degradation, and replacement. this is loosely what creates a constituatively expressed proteome. the S protien is not part of the program so is degraded and not replaced. if the protien insertion is too extensive or the activity of the protien is egregious for the cell then, apoptosis
- throw9678 6y ago
  If you (or others) would humor a newbie question - assuming that host cells start expressing the spike protein, and the immune system learns to react to it, what are the chances that it will also learn to react to other proteins expressed by those cells, which are not related to the virus, and basically learn to attack its own cells? 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?
  - rolph 6y ago
    there is a self recognition system, the body indexes its components and will end process when the protien is recognized as self. foriegn molecules are not indexed and if large enough [as in protiens, not water or salt] they will trigger immune response a wanted poster and a bunch of antibodies are produced that tag the invader. 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: https://en.wikipedia.org/wiki/Immunology https://en.wikipedia.org/wiki/Immunology https://en.wikipedia.org/wiki/Autoimmune_disease https://en.wikipedia.org/wiki/Autoimmune_disease
    - stmfreak 6y ago
      Where does the body store this index of components recognized as self?
      - deleted 6y ago
        [deleted]
      - rolph 6y ago
        this is a million dollar question probably nobel prize winning. 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 .
- ashleyn 6y ago
  Pardon my ignorance but is this something that could, in theory, trigger a cell to become cancerous or trigger the body to develop an autoimmune condition (as the spike protein is created by the body's own cells)?
  - rolph 6y ago
    short answer, is no 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.
nextos 6y ago
The mRNA gets translated into the spike protein. And then the cell presents it in the surface for the immune cells to track and learn it. This is called MHC-I pathway. As a consequence of this, the immune system might instruct "infected" cells to self-destruction. 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/art%3A10.1038%2Fs41392-020-00352-y/MediaObjects/41392_2020_352_Fig2_HTML.png https://media.springernature.com/lw685/springer-static/image...
stmfreak 6y ago
These are great questions. Another one since we are talking about editing the programming “code” of the human body is: what if we got it wrong? What sorts of “bugs” might occur in execution or through unforeseen interactions?
- exmadscientist 6y ago
  > Another one since we are talking about editing the programming “code” of the human body is ...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.
  - whycombagator 6y ago
    > 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?
    - aponia 6y ago
      Here is an article on Covid vaccines, and the second link is from its references, and explains lipid nanoparticles used in these vaccines. Both the Pfizer and Moderna vaccines use lipid nanoparticles and are very similar in their designs. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583697/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583697/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624045/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624045/ ______________________________________________________ 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-vaccines-07-00132title https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963972/#sec3-v...

by lrossi 6y ago

rolph 6y ago

its a game of numbers and timing. first off there is a patrol inside that cell that cleans up mRNA that doesnt have a "hall pass" cells that are very damaged or confused will go into a procedural death mode called apoptosis, different from simple cell death as others are imformed of events and can react accordingly. 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

rolph 6y ago
addendum >>there is a halflife/turnover rate, in tech terms the hardware is updated very frequently, by degradation, and replacement. this is loosely what creates a constituatively expressed proteome. the S protien is not part of the program so is degraded and not replaced. if the protien insertion is too extensive or the activity of the protien is egregious for the cell then, apoptosis
throw9678 6y ago
If you (or others) would humor a newbie question - assuming that host cells start expressing the spike protein, and the immune system learns to react to it, what are the chances that it will also learn to react to other proteins expressed by those cells, which are not related to the virus, and basically learn to attack its own cells? 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?
- rolph 6y ago
  there is a self recognition system, the body indexes its components and will end process when the protien is recognized as self. foriegn molecules are not indexed and if large enough [as in protiens, not water or salt] they will trigger immune response a wanted poster and a bunch of antibodies are produced that tag the invader. 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: https://en.wikipedia.org/wiki/Immunology https://en.wikipedia.org/wiki/Immunology https://en.wikipedia.org/wiki/Autoimmune_disease https://en.wikipedia.org/wiki/Autoimmune_disease
  - stmfreak 6y ago
    Where does the body store this index of components recognized as self?
    - deleted 6y ago
      [deleted]
    - rolph 6y ago
      this is a million dollar question probably nobel prize winning. 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 .
ashleyn 6y ago
Pardon my ignorance but is this something that could, in theory, trigger a cell to become cancerous or trigger the body to develop an autoimmune condition (as the spike protein is created by the body's own cells)?
- rolph 6y ago
  short answer, is no 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.

nextos 6y ago

The mRNA gets translated into the spike protein. And then the cell presents it in the surface for the immune cells to track and learn it. This is called MHC-I pathway. As a consequence of this, the immune system might instruct "infected" cells to self-destruction. 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/art%3A10.1038%2Fs41392-020-00352-y/MediaObjects/41392_2020_352_Fig2_HTML.png https://media.springernature.com/lw685/springer-static/image...

stmfreak 6y ago

These are great questions. Another one since we are talking about editing the programming “code” of the human body is: what if we got it wrong? What sorts of “bugs” might occur in execution or through unforeseen interactions?

exmadscientist 6y ago
> Another one since we are talking about editing the programming “code” of the human body is ...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.
- whycombagator 6y ago
  > 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?
  - aponia 6y ago
    Here is an article on Covid vaccines, and the second link is from its references, and explains lipid nanoparticles used in these vaccines. Both the Pfizer and Moderna vaccines use lipid nanoparticles and are very similar in their designs. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583697/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583697/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624045/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624045/ ______________________________________________________ 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-vaccines-07-00132title https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963972/#sec3-v...