5 ms·

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, wha

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 .
    - darkwizard42 6y ago
      This has been an AWESOME thread to follow. Thanks for taking the time to answer through the thread.
      - divbzero 6y ago
        Yes. Reading the thread you quickly realize what a natural wonder our immune system is, and how much more there may be left to learn about it.
  - nicwilson 6y ago
    They are made by https://en.wikipedia.org/wiki/Thymic_epithelial_cell https://en.wikipedia.org/wiki/Thymic_epithelial_cell (see the section on Positive and negative selection) as part of the selection process.
  - m4rtink 6y ago
    There is a guy living in a house inside a tree with huge library. The first responder cells will call him by phone and he will check the library for what to do. Disclaimer: All I know about this comes from Cells at Work/Hataraku Saibou. (https://en.m.wikipedia.org/wiki/Cells_at_Work https://en.m.wikipedia.org/wiki/Cells_at_Work!)
  - deleted 6y ago
    [deleted]
  - ddmma 6y ago
    “The body stores this index of components recognized as self in the thymus” / gtp3 gets more specific
  - wetpaws 6y ago
    It does not. All index entries that correspond to body are filtered out during aging process. If some are missed or close enough to the body proteins past puberty, you would get an autoimmune reaction
    - rolph 6y ago
      look back in the thread and you will see this part is about an autoimmune question. other than that yes you have the concept.
- throw9678 6y ago
  I know just enough to be dangerous :) I actually have an autoimmune disease, so that's the reason for my question, specifically wondering about the chance for an MRNA vaccine triggering or deepening autoimmune disease. 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! :)
  - sgfyd 6y ago
    > specifically wondering about the chance for an MRNA vaccine triggering or deepening autoimmune disease. 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.
    - rolph 6y ago
      i have a friend that is quite allergic to aluminum, and zinc on contact. these sort of allergies are about hypersensativity, it sounds like you may have problems with any sort of foriegn challenge to your body. A major component of most vaccines is an adjuvent and that is intended to make your immune system extremely ready to recognize foriegn antigens. this means a very good chance you will have a flare up. you want to have sound medical advice from a doctor regarding your own health characteristics. Bare minimum i would want to see direct supervision and observation after a vaccine.
      - sgfyd 6y ago
        Allergic reactions to adjuvants is an entirely different matter (than autoimmune reactions) and may actually not apply to these vaccines. This just goes to show, don't get your medical advice from HN.
nicwilson 6y ago
> assuming that host cells start expressing the spike protein, and the immune system learns to react to it, 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.
- sgfyd 6y ago
  > as the mRNA is not reverse transcribed into DNA and reintegrated into the genome Why not? Just because it doesn't match up, or is there a deeper reason?
  - rolph 6y ago
    an enzyme called reverse transcriptase or its equivalent is required, the HIV virus and a number of other retrovirii do this, and implant thier code into the host DNA. 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.
  - nicwilson 6y ago
    because thats not what mRNA and normal cellular processes do and there is no mechanism in the body to allow that to happen. 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.
- curlypaul924 6y ago
wiml 6y ago
My understanding is that normal viral infections cause proteins to be expressed by cells in the same way — in fact, uninfected cells also continually display a "status report" of protein fragments. Your immune system monitors this to detect cells that have gone haywire, whether by mutation or infection. https://en.wikipedia.org/wiki/MHC_class_I#Effect_of_viruses 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.
- rolph 6y ago
  this is a very new and edgey statement however here goes. the self/nonself antigen profile is likely in the DNA and in eukaryotes likely functions in similar fashion to the NORMAL crspr system of prokaryotes [as in not the hijacked gene editing one of current topic] keep in mind there is no proof yet that this is how it works but it is a promissing direction to look into.
jcynix 6y ago
If one gets infected with COVID19, the cells containg the virus will too produce the spike protein among other virus constituents as specified by the virus RNA. 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?
- rolph 6y ago
  this is hard to say yes, but i can tell you that the live virus will replicate in the cell and increase copy number of its RNA until the cell dies. the vaccine mRNA will remain until degraded and stop producing valid copies. 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

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 .
  - darkwizard42 6y ago
    This has been an AWESOME thread to follow. Thanks for taking the time to answer through the thread.
    - divbzero 6y ago
      Yes. Reading the thread you quickly realize what a natural wonder our immune system is, and how much more there may be left to learn about it.
- nicwilson 6y ago
  They are made by https://en.wikipedia.org/wiki/Thymic_epithelial_cell https://en.wikipedia.org/wiki/Thymic_epithelial_cell (see the section on Positive and negative selection) as part of the selection process.
- m4rtink 6y ago
  There is a guy living in a house inside a tree with huge library. The first responder cells will call him by phone and he will check the library for what to do. Disclaimer: All I know about this comes from Cells at Work/Hataraku Saibou. (https://en.m.wikipedia.org/wiki/Cells_at_Work https://en.m.wikipedia.org/wiki/Cells_at_Work!)
- deleted 6y ago
  [deleted]
- ddmma 6y ago
  “The body stores this index of components recognized as self in the thymus” / gtp3 gets more specific
- wetpaws 6y ago
  It does not. All index entries that correspond to body are filtered out during aging process. If some are missed or close enough to the body proteins past puberty, you would get an autoimmune reaction
  - rolph 6y ago
    look back in the thread and you will see this part is about an autoimmune question. other than that yes you have the concept.
throw9678 6y ago
I know just enough to be dangerous :) I actually have an autoimmune disease, so that's the reason for my question, specifically wondering about the chance for an MRNA vaccine triggering or deepening autoimmune disease. 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! :)
- sgfyd 6y ago
  > specifically wondering about the chance for an MRNA vaccine triggering or deepening autoimmune disease. 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.
  - rolph 6y ago
    i have a friend that is quite allergic to aluminum, and zinc on contact. these sort of allergies are about hypersensativity, it sounds like you may have problems with any sort of foriegn challenge to your body. A major component of most vaccines is an adjuvent and that is intended to make your immune system extremely ready to recognize foriegn antigens. this means a very good chance you will have a flare up. you want to have sound medical advice from a doctor regarding your own health characteristics. Bare minimum i would want to see direct supervision and observation after a vaccine.
    - sgfyd 6y ago
      Allergic reactions to adjuvants is an entirely different matter (than autoimmune reactions) and may actually not apply to these vaccines. This just goes to show, don't get your medical advice from HN.

nicwilson 6y ago

> assuming that host cells start expressing the spike protein, and the immune system learns to react to it, 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.

sgfyd 6y ago
> as the mRNA is not reverse transcribed into DNA and reintegrated into the genome Why not? Just because it doesn't match up, or is there a deeper reason?
- rolph 6y ago
  an enzyme called reverse transcriptase or its equivalent is required, the HIV virus and a number of other retrovirii do this, and implant thier code into the host DNA. 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.
- nicwilson 6y ago
  because thats not what mRNA and normal cellular processes do and there is no mechanism in the body to allow that to happen. 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.
curlypaul924 6y ago

wiml 6y ago

My understanding is that normal viral infections cause proteins to be expressed by cells in the same way — in fact, uninfected cells also continually display a "status report" of protein fragments. Your immune system monitors this to detect cells that have gone haywire, whether by mutation or infection. https://en.wikipedia.org/wiki/MHC_class_I#Effect_of_viruses 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.

rolph 6y ago
this is a very new and edgey statement however here goes. the self/nonself antigen profile is likely in the DNA and in eukaryotes likely functions in similar fashion to the NORMAL crspr system of prokaryotes [as in not the hijacked gene editing one of current topic] keep in mind there is no proof yet that this is how it works but it is a promissing direction to look into.

jcynix 6y ago

If one gets infected with COVID19, the cells containg the virus will too produce the spike protein among other virus constituents as specified by the virus RNA. 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?

rolph 6y ago
this is hard to say yes, but i can tell you that the live virus will replicate in the cell and increase copy number of its RNA until the cell dies. the vaccine mRNA will remain until degraded and stop producing valid copies. 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