5 ms·

I just finished up an introductory biology lecture series, and this suddenly makes less sense to me than it did before. What is it about the foreign cells that

I just finished up an introductory biology lecture series, and this suddenly makes less sense to me than it did before. What is it about the foreign cells that is identified as foreign by the host cells? The cells ought to be remarkably similar. They're human, with the same function/pluripotency using the same protein interactions. So why attack it?

ceejayoz 7y ago
There's a lot more to immune response than "does this look like a human cell?" See, for example, blood types, where giving an A type person B type blood will cause serious issues. Each human has a largely unique signature of HLAs (https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Human_leukocyte_antigen).
- cabalamat 7y ago
  The whole point of this, evolutionarily, is so that a parasite that thrived in one human body won't necessarily thrive in another. This is also why many species reproduce by sex.
Enginerrrd 7y ago
Because it's part of the arms race with pathogens that has been going on for a billion years since multi-cellular life first appeared. Pathogens do lots of very clever things to hide from the immune system, so the immune system is tuned to detect very subtle changes. The body largely operates on zero-trust network models, except for a few locations where the benefit of a too-active immune system has serious consequences to the fitness of the organism. The eyes and the testicles are good examples of that in humans.
- asveikau 7y ago
  I guess auto-immune disease is an example of where it also goes the wrong way for somebody. Probably most of us know somebody with IBD, lupus, or any of the others. It's very common for the body to reject something benign, or ourselves.
  - friedegg 7y ago
    Type 1 diabetes is a good example of this, where the body detects its own insulin producing cells as threats and eliminates them. Lots of the research in type 1 treatments isn't just about producing insulin, but figuring out how to prevent the body from destroying it again without all of the risks of immunosupressant drugs.
- wongarsu 7y ago
  To add to this: if the immune system would just check that the cell is human then every invader would just evolve to pass that check. The only viable way to defend is to mark the cells as belonging to this specific human. That way even if some bacteria evolves to trick my immune system it's unlikely to also trick yours, and the infection can't spread.
  - alan-crowe 7y ago
    Additionally, if the immune system would just check that the cell is human, then humans would be vulnerable to contagious cancer, such as the facial tumor disease suffered by Tasmanian Devils https://en.wikipedia.org/wiki/Devil_facial_tumour_disease https://en.wikipedia.org/wiki/Devil_facial_tumour_disease
    - mkl 7y ago
      Humans almost certainly are vulnerable to contagious cancer (there are a few known in other species: https://en.wikipedia.org/wiki/Clonally_transmissible_cancer https://en.wikipedia.org/wiki/Clonally_transmissible_cancer) . We just haven't acquired/discovered any yet.
      - apathy 7y ago
        HTLV, EBV, HPV you better believe we have! It’s just rare (thank goodness).
        skosch 7y ago
        Those are cancers caused by viruses, and it's the viruses getting transmitted. On the other hand, clonal transmission refers to the cancer cells themselves leaving sick individual A, entering healthy individual B, and continuing to reproduce there.
        apathy 7y ago
        You could use transmissible preleukemia (eg CHIP in allo transplants) as an example if you wished. Direct unassisted clonal transmission in humans seems likely but, as you noted, it hasn’t been documented to the extent that Tasmanian Devil facial tumors have. Warts are a corner case. I’m not sure whether it’s been determined if some hosts end up increasing the fitness of the shed cells. If so, that’s quickly heading towards a globally transmitted precursor lesion.
- jacobolus 7y ago
  > except for a few locations where the benefit of a too-active immune system has serious consequences For anyone else curious about this, https://en.wikipedia.org/wiki/Immune_privilege https://en.wikipedia.org/wiki/Immune_privilege
ryanmercer 7y ago
This seems to answer it https://www.sciencealert.com/this-protein-could-explain-why-our-bodies-reject-transplanted-organs https://www.sciencealert.com/this-protein-could-explain-why-... Dendritic cells 'teach' lymphocytes what a foreign invader is, right most of us know that from high school, but here's where it goes beyond me: >They found that differences between the mice donor's and recipient's SIRPα gene correlated with the recipient's immune responses. SIRPα isn't an unknown protein, already understood to bind to another protein called CD47 that triggers a range of immune responses in different white blood cells. >Joining the dots, the researchers believe CD47 on monocytes – the white blood cells that grow into dendritic cells – interact with SIRPα receptors on foreign tissues, setting off the entire ID check process. >"Once these cells are activated, then they turn around and activate the rest of the immune system, and that leads to the full-blown rejection of the organ," lead researcher Fadi Lakkis from the University of Pittsburgh told Liz Reid at 90.5 WESA. Here's the paper https://immunology.sciencemag.org/content/2/12/eaam6202 https://immunology.sciencemag.org/content/2/12/eaam6202 This seems to be the relevant bit >Using an elegant positional cloning approach, Dai et al. have identified polymorphisms in the mouse gene encoding signal regulatory protein α (SIRPα) to be key in this innate self-nonself recognition. They show that SIRPα receptor CD47 binds SIRPα variants with distinct affinities and propose this affinity sensing to be the mechanism that triggers dendritic cell maturation, the first step in the initiation of the alloimmune response. Given that the SIRPα gene is also polymorphic in humans, it remains to be seen whether human SIRPα variations influence transplantation success.
aphextim 7y ago
Probably has some sort of MAC address identifier that can detect whether something if different than the host DNA, but I have no idea nor experience in biology.
- xwdv 7y ago
  I’d say it’s probably more like some kind of checksum against the DNA. If the body detects something has been changed from what was there before it dispatches the white blood cells to kill it off. Immunosuppressants are a way to bypass the checksum, but only for some limited time. Maybe we need a way to change the checksum values altogether, but then the whole body could be rendered rejected and cease to function (death).
  - petschge 7y ago
    This is actually an issue in graft-vs-host rejection for bone marrow transplants.
  - aphextim 7y ago
    I love tech analogies to biological functions. It amazes me how much 'tech' is always running on a cellular/molecular level. Thank you!
    - SamBam 7y ago
      We always reach for the analogies that match our experience most closely. If this were 200 years ago, we'd say that the immune system was like a lock-and-key mechanism, or perhaps we'd say it was like a bank checking for correct signatures. Indeed, I remember a kid's cartoon about our bodies when I was growing up that showed germs that had evolved the correct antigens as being spies passing through passport control with forged passports.
    - magicalhippo 7y ago
      Indeed. I had read about it before but viewing these visualizations blew my mind: https://www.youtube.com/watch?v=SMtWvDbfHLo https://www.youtube.com/watch?v=SMtWvDbfHLo (DNA transcription) https://www.youtube.com/watch?v=TfYf_rPWUdY https://www.youtube.com/watch?v=TfYf_rPWUdY (mRNA translation) https://www.youtube.com/watch?v=I9ArIJWYZHI https://www.youtube.com/watch?v=I9ArIJWYZHI (DNA replication)
abbirdboy 7y ago
Adding to some of the other comments: Leukocytes (immune cells) such as B and T cells will undergo "education" when they are developing. For example, B cells, before being released, will go through something called central tolerance in the bone marrow. If the B cell receptors bind a "self" antigen (markers that are associated with our own cells) while developing, it will go through negative selection and be destroyed. Of course, some B cells that bind self antigens do make it through in rare cases and this is what manifests as an autoimmune disease.
- airstrike 7y ago
  Thanks for this. I'm perpetually amazed at how mind-bogglingly complex the human body is. > while developing, it will go through negative selection and be destroyed Can you share more about how this process works? Even just a link would do. Thank you!
  - Footkerchief 7y ago
    https://en.wikipedia.org/wiki/V(D)J_recombination https://en.wikipedia.org/wiki/V(D)J_recombination
  - abbirdboy 7y ago
    I think Khan Academy does a good job of explaining it: https://www.youtube.com/watch?v=EsQyCHs4IBY https://www.youtube.com/watch?v=EsQyCHs4IBY
- deleted 7y ago
  [deleted]
refurb 7y ago
Proteins on the surface of cells identify them as “self” or “not self”. MHC (major histocompatability complex) plays a large role.
DoreenMichele 7y ago
So why attack it? There is more in your body than just your cells. We are in the infancy of understanding stuff like this, but my WAG is that donor tissue can be rejected because it contains hostile microorganisms that didn't make the radar of the medical staff for whatever reason.
- zbentley 7y ago
  > donor tissue can be rejected because it contains hostile microorganisms Citation? That sounds both convenient and implausible (medical science has a long way to go in many areas, but microscopy/microorganism detection is pretty far along).
  - DoreenMichele 7y ago
    Humans Carry More Bacterial Cells than Human Ones https://www.scientificamerican.com/article/strange-but-true-humans-carry-more-bacterial-cells-than-human-ones/ https://www.scientificamerican.com/article/strange-but-true-... FYI: WAG stands for Wild Ass Guess. They usually don't involve citations.
echelon 7y ago
> I just finished up an introductory biology lecture series, and this suddenly makes less sense to me than it did before. The immune system is one of the most complicated and wonderful pieces of biology. It's also scary in the ways that it can malfunction and the challenges it presents to modern medicine. > What is it about the foreign cells that is identified as foreign by the host cells? The MHC system is a major determinant of histocompatibility. https://en.wikipedia.org/wiki/Major_histocompatibility_complex https://en.wikipedia.org/wiki/Major_histocompatibility_compl... https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Histocompatibility https://en.wikipedia.org/wiki/Histocompatibility MHC is an adaptive immune function used to detect foreign antigen that was evolved as a means to combat intracellular pathogens. This cell-surface machinery collects and presents foreign antigens from inside the cell at the cell surface for discovery by immune cells that come into contact. If something "foreign" is found on the MHC, the immune system targets the cell for deletion and upregulates the immune system for further attack. The genes that code the MHC proteins vary widely between individuals. This can be beneficial as viruses struggle to evolve in a way that evades all MHCs in a population. Unfortunately, the MHC proteins are themselves a highly reactive antigen that triggers the immune system. Luckily, the body learns during a process called "negative selection" to cull any immune cell receptors that recognize your own MHCs: https://en.wikipedia.org/wiki/Thymus https://en.wikipedia.org/wiki/Thymus (search "negative selection"). If any of your own T-cells match your own MHC, they're killed. Unfortunately, your body doesn't know the shape of MHC proteins from donor tissue and can't learn to kill any TCRs that match. And these proteins are incredibly, incredibly polymorphic: https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Human_leukocyte_antigen Search "variability", then multiply the numbers -- you're not going to find an exact match for you anywhere, unless you have an identical twin. This is why donor databases exist. If you can find a match for one of the variants, it reduces the product of these multiples. It's very hard to find a tissue match. When you transplant foreign tissue, it's an antigen. Fun fact: did you know your immune system genes aren't at rest and are actually evolving right now? Your immune cells run stochastic hill climbing. It's wild. Check out somatic recombination: https://en.wikipedia.org/wiki/V(D)J_recombination https://en.wikipedia.org/wiki/V(D)J_recombination The immune system is incredibly complicated.
- 7y ago
onemoresoop 7y ago
My understanding is that most cells in the human body regenerate. What I don't understand is how cells that are part of the transplant regenerate. Do they use the host or the transplanted DNA to regenerate?
- PeterisP 7y ago
  Cells (re)generate by splitting, there's no other way. For non-mobile tissue, the tissue regenerates itself from whatever DNA the cells in that tissue have locally. There are some types of cells that are "manufactured" in one place and "shipped" throughout the body (e.g. blood cells in bone marrow) but for the transplanted tissue any new cells would still have the donor DNA forever. Also, that applies for chimeric humans that happen to have two different DNA sets from two different fertilized eggs; some parts of their body will forever have different DNA than other parts.
  - insulanus 7y ago
    > Also, that applies for hymeric humans Seems like this: https://en.wikipedia.org/wiki/Chimera_(genetics) https://en.wikipedia.org/wiki/Chimera_(genetics)
    - PeterisP 7y ago
      Yep, that's the correct term, English isn't my main language.
  - onemoresoop 7y ago
    Now makes more sense. Thanks for the explaination
bitwize 7y ago
It's no one thing, but a combination of factors that allow the immune system to identify and attack foreign cells that have entered the system. Think of it like one of those incredibly stupid algorithms that pass for AI today. Except this algorithm is "trained" over millions of years by the host organism dying when it fails to properly classify hostile foreign biomass. Over that long a time it gets to be pretty good, but not 100% flawless: autoimmune disorders like multiple sclerosis result when the immune system incorrectly attacks the body's own tissues, and allergies result when the immune system overreacts to foreign material, such as food or pollen, entering the body.

ceejayoz 7y ago

There's a lot more to immune response than "does this look like a human cell?" See, for example, blood types, where giving an A type person B type blood will cause serious issues. Each human has a largely unique signature of HLAs (https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Human_leukocyte_antigen).

cabalamat 7y ago
The whole point of this, evolutionarily, is so that a parasite that thrived in one human body won't necessarily thrive in another. This is also why many species reproduce by sex.

Enginerrrd 7y ago

Because it's part of the arms race with pathogens that has been going on for a billion years since multi-cellular life first appeared. Pathogens do lots of very clever things to hide from the immune system, so the immune system is tuned to detect very subtle changes. The body largely operates on zero-trust network models, except for a few locations where the benefit of a too-active immune system has serious consequences to the fitness of the organism. The eyes and the testicles are good examples of that in humans.

asveikau 7y ago
I guess auto-immune disease is an example of where it also goes the wrong way for somebody. Probably most of us know somebody with IBD, lupus, or any of the others. It's very common for the body to reject something benign, or ourselves.
- friedegg 7y ago
  Type 1 diabetes is a good example of this, where the body detects its own insulin producing cells as threats and eliminates them. Lots of the research in type 1 treatments isn't just about producing insulin, but figuring out how to prevent the body from destroying it again without all of the risks of immunosupressant drugs.
wongarsu 7y ago
To add to this: if the immune system would just check that the cell is human then every invader would just evolve to pass that check. The only viable way to defend is to mark the cells as belonging to this specific human. That way even if some bacteria evolves to trick my immune system it's unlikely to also trick yours, and the infection can't spread.
- alan-crowe 7y ago
  Additionally, if the immune system would just check that the cell is human, then humans would be vulnerable to contagious cancer, such as the facial tumor disease suffered by Tasmanian Devils https://en.wikipedia.org/wiki/Devil_facial_tumour_disease https://en.wikipedia.org/wiki/Devil_facial_tumour_disease
  - mkl 7y ago
    Humans almost certainly are vulnerable to contagious cancer (there are a few known in other species: https://en.wikipedia.org/wiki/Clonally_transmissible_cancer https://en.wikipedia.org/wiki/Clonally_transmissible_cancer) . We just haven't acquired/discovered any yet.
    - apathy 7y ago
      HTLV, EBV, HPV you better believe we have! It’s just rare (thank goodness).
      - skosch 7y ago
        Those are cancers caused by viruses, and it's the viruses getting transmitted. On the other hand, clonal transmission refers to the cancer cells themselves leaving sick individual A, entering healthy individual B, and continuing to reproduce there.
        apathy 7y ago
        You could use transmissible preleukemia (eg CHIP in allo transplants) as an example if you wished. Direct unassisted clonal transmission in humans seems likely but, as you noted, it hasn’t been documented to the extent that Tasmanian Devil facial tumors have. Warts are a corner case. I’m not sure whether it’s been determined if some hosts end up increasing the fitness of the shed cells. If so, that’s quickly heading towards a globally transmitted precursor lesion.
jacobolus 7y ago
> except for a few locations where the benefit of a too-active immune system has serious consequences For anyone else curious about this, https://en.wikipedia.org/wiki/Immune_privilege https://en.wikipedia.org/wiki/Immune_privilege

ryanmercer 7y ago

This seems to answer it https://www.sciencealert.com/this-protein-could-explain-why-our-bodies-reject-transplanted-organs https://www.sciencealert.com/this-protein-could-explain-why-... Dendritic cells 'teach' lymphocytes what a foreign invader is, right most of us know that from high school, but here's where it goes beyond me: >They found that differences between the mice donor's and recipient's SIRPα gene correlated with the recipient's immune responses. SIRPα isn't an unknown protein, already understood to bind to another protein called CD47 that triggers a range of immune responses in different white blood cells. >Joining the dots, the researchers believe CD47 on monocytes – the white blood cells that grow into dendritic cells – interact with SIRPα receptors on foreign tissues, setting off the entire ID check process. >"Once these cells are activated, then they turn around and activate the rest of the immune system, and that leads to the full-blown rejection of the organ," lead researcher Fadi Lakkis from the University of Pittsburgh told Liz Reid at 90.5 WESA. Here's the paper https://immunology.sciencemag.org/content/2/12/eaam6202 https://immunology.sciencemag.org/content/2/12/eaam6202 This seems to be the relevant bit >Using an elegant positional cloning approach, Dai et al. have identified polymorphisms in the mouse gene encoding signal regulatory protein α (SIRPα) to be key in this innate self-nonself recognition. They show that SIRPα receptor CD47 binds SIRPα variants with distinct affinities and propose this affinity sensing to be the mechanism that triggers dendritic cell maturation, the first step in the initiation of the alloimmune response. Given that the SIRPα gene is also polymorphic in humans, it remains to be seen whether human SIRPα variations influence transplantation success.

aphextim 7y ago

Probably has some sort of MAC address identifier that can detect whether something if different than the host DNA, but I have no idea nor experience in biology.

xwdv 7y ago
I’d say it’s probably more like some kind of checksum against the DNA. If the body detects something has been changed from what was there before it dispatches the white blood cells to kill it off. Immunosuppressants are a way to bypass the checksum, but only for some limited time. Maybe we need a way to change the checksum values altogether, but then the whole body could be rendered rejected and cease to function (death).
- petschge 7y ago
  This is actually an issue in graft-vs-host rejection for bone marrow transplants.
- aphextim 7y ago
  I love tech analogies to biological functions. It amazes me how much 'tech' is always running on a cellular/molecular level. Thank you!
  - SamBam 7y ago
    We always reach for the analogies that match our experience most closely. If this were 200 years ago, we'd say that the immune system was like a lock-and-key mechanism, or perhaps we'd say it was like a bank checking for correct signatures. Indeed, I remember a kid's cartoon about our bodies when I was growing up that showed germs that had evolved the correct antigens as being spies passing through passport control with forged passports.
  - magicalhippo 7y ago
    Indeed. I had read about it before but viewing these visualizations blew my mind: https://www.youtube.com/watch?v=SMtWvDbfHLo https://www.youtube.com/watch?v=SMtWvDbfHLo (DNA transcription) https://www.youtube.com/watch?v=TfYf_rPWUdY https://www.youtube.com/watch?v=TfYf_rPWUdY (mRNA translation) https://www.youtube.com/watch?v=I9ArIJWYZHI https://www.youtube.com/watch?v=I9ArIJWYZHI (DNA replication)

abbirdboy 7y ago

Adding to some of the other comments: Leukocytes (immune cells) such as B and T cells will undergo "education" when they are developing. For example, B cells, before being released, will go through something called central tolerance in the bone marrow. If the B cell receptors bind a "self" antigen (markers that are associated with our own cells) while developing, it will go through negative selection and be destroyed. Of course, some B cells that bind self antigens do make it through in rare cases and this is what manifests as an autoimmune disease.

airstrike 7y ago
Thanks for this. I'm perpetually amazed at how mind-bogglingly complex the human body is. > while developing, it will go through negative selection and be destroyed Can you share more about how this process works? Even just a link would do. Thank you!
- Footkerchief 7y ago
  https://en.wikipedia.org/wiki/V(D)J_recombination https://en.wikipedia.org/wiki/V(D)J_recombination
- abbirdboy 7y ago
  I think Khan Academy does a good job of explaining it: https://www.youtube.com/watch?v=EsQyCHs4IBY https://www.youtube.com/watch?v=EsQyCHs4IBY
deleted 7y ago
[deleted]

refurb 7y ago

Proteins on the surface of cells identify them as “self” or “not self”. MHC (major histocompatability complex) plays a large role.

DoreenMichele 7y ago

So why attack it? There is more in your body than just your cells. We are in the infancy of understanding stuff like this, but my WAG is that donor tissue can be rejected because it contains hostile microorganisms that didn't make the radar of the medical staff for whatever reason.

zbentley 7y ago
> donor tissue can be rejected because it contains hostile microorganisms Citation? That sounds both convenient and implausible (medical science has a long way to go in many areas, but microscopy/microorganism detection is pretty far along).
- DoreenMichele 7y ago
  Humans Carry More Bacterial Cells than Human Ones https://www.scientificamerican.com/article/strange-but-true-humans-carry-more-bacterial-cells-than-human-ones/ https://www.scientificamerican.com/article/strange-but-true-... FYI: WAG stands for Wild Ass Guess. They usually don't involve citations.

echelon 7y ago

> I just finished up an introductory biology lecture series, and this suddenly makes less sense to me than it did before. The immune system is one of the most complicated and wonderful pieces of biology. It's also scary in the ways that it can malfunction and the challenges it presents to modern medicine. > What is it about the foreign cells that is identified as foreign by the host cells? The MHC system is a major determinant of histocompatibility. https://en.wikipedia.org/wiki/Major_histocompatibility_complex https://en.wikipedia.org/wiki/Major_histocompatibility_compl... https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Histocompatibility https://en.wikipedia.org/wiki/Histocompatibility MHC is an adaptive immune function used to detect foreign antigen that was evolved as a means to combat intracellular pathogens. This cell-surface machinery collects and presents foreign antigens from inside the cell at the cell surface for discovery by immune cells that come into contact. If something "foreign" is found on the MHC, the immune system targets the cell for deletion and upregulates the immune system for further attack. The genes that code the MHC proteins vary widely between individuals. This can be beneficial as viruses struggle to evolve in a way that evades all MHCs in a population. Unfortunately, the MHC proteins are themselves a highly reactive antigen that triggers the immune system. Luckily, the body learns during a process called "negative selection" to cull any immune cell receptors that recognize your own MHCs: https://en.wikipedia.org/wiki/Thymus https://en.wikipedia.org/wiki/Thymus (search "negative selection"). If any of your own T-cells match your own MHC, they're killed. Unfortunately, your body doesn't know the shape of MHC proteins from donor tissue and can't learn to kill any TCRs that match. And these proteins are incredibly, incredibly polymorphic: https://en.wikipedia.org/wiki/Human_leukocyte_antigen https://en.wikipedia.org/wiki/Human_leukocyte_antigen Search "variability", then multiply the numbers -- you're not going to find an exact match for you anywhere, unless you have an identical twin. This is why donor databases exist. If you can find a match for one of the variants, it reduces the product of these multiples. It's very hard to find a tissue match. When you transplant foreign tissue, it's an antigen. Fun fact: did you know your immune system genes aren't at rest and are actually evolving right now? Your immune cells run stochastic hill climbing. It's wild. Check out somatic recombination: https://en.wikipedia.org/wiki/V(D)J_recombination https://en.wikipedia.org/wiki/V(D)J_recombination The immune system is incredibly complicated.

7y ago

onemoresoop 7y ago

My understanding is that most cells in the human body regenerate. What I don't understand is how cells that are part of the transplant regenerate. Do they use the host or the transplanted DNA to regenerate?

PeterisP 7y ago
Cells (re)generate by splitting, there's no other way. For non-mobile tissue, the tissue regenerates itself from whatever DNA the cells in that tissue have locally. There are some types of cells that are "manufactured" in one place and "shipped" throughout the body (e.g. blood cells in bone marrow) but for the transplanted tissue any new cells would still have the donor DNA forever. Also, that applies for chimeric humans that happen to have two different DNA sets from two different fertilized eggs; some parts of their body will forever have different DNA than other parts.
- insulanus 7y ago
  > Also, that applies for hymeric humans Seems like this: https://en.wikipedia.org/wiki/Chimera_(genetics) https://en.wikipedia.org/wiki/Chimera_(genetics)
  - PeterisP 7y ago
    Yep, that's the correct term, English isn't my main language.
- onemoresoop 7y ago
  Now makes more sense. Thanks for the explaination

bitwize 7y ago

It's no one thing, but a combination of factors that allow the immune system to identify and attack foreign cells that have entered the system. Think of it like one of those incredibly stupid algorithms that pass for AI today. Except this algorithm is "trained" over millions of years by the host organism dying when it fails to properly classify hostile foreign biomass. Over that long a time it gets to be pretty good, but not 100% flawless: autoimmune disorders like multiple sclerosis result when the immune system incorrectly attacks the body's own tissues, and allergies result when the immune system overreacts to foreign material, such as food or pollen, entering the body.