Is this true that it is inevitable? My understanding, from my girlfriend attending medical school (only M1), is that for many types of transplants, when immunosupressants are taken properly, it is unlikely that the organ will ever be rejected.
For example, only 10-20% of patients who receive a kidney transplant will experience rejection.
It's kind of similar to how diabetes patients need to constantly monitor their blood sugar and manually adjust their insulin levels to compensate, but on a longer time scale (generally weeks to months rather than minutes to hours). But with diabetes, at least you have the potential for almost direct control over your blood sugar levels (by regulating food intake). There is no such direct control for your level of immune activity, nor is there a simple and quick blood test to measure whether immune suppression is at the right level.
In short, anyone with a transplant is walking a wobbly tightrope of immune suppression for the rest of their life, and they sometimes don't even know they've fallen off until they hit the ground.
(Source: I have previously worked in a lab studying transplant rejection and trying to, among other things, develop such a simple and quick blood test: https://www.ncbi.nlm.nih.gov/pubmed/24725967)
Modern immunosuppressive therapy for, for instance kidneys, has dropped the five year acute rejection rate from 50% to 20%. About 8-10% in the first year.
You can get a 5% 10-year non-rejection rate only in the most hand-picked groups (adheres to meds, no underlying systemic disease, and no chronic nephropathy). That sub-population exists, but it’s pretty uncommon.
The parent comment I responded to stated it was "inevitable." "Inevitable" and "only 20%" are many more worlds apart than "unlikely to ever be rejected" and "only 20%".
"Unlikely" is a bit subjective, but it is well below a coin flip.
I cited a source for the statistics. If you disagree, can you please cite your source?
you better believe we have! It’s just rare (thank goodness).
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.
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.
For anyone else curious about this, https://en.wikipedia.org/wiki/Immune_privilege
> 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!
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).
This is also why many species reproduce by sex.
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
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.
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.
Seems like this:
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.
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 (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:
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:
The immune system is incredibly complicated.
> Unfortunately, the MHC proteins are themselves a highly reactive antigen thahttps://www.airships.net/hindenburg/interiors/t 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:
This is very interesting that this process is split into two separate domains / privilege levels. That way you can't have a fork bomb that would overwhelm the MHC production process.
> Unfortunately, your body doesn't know the shape of MHC proteins from donor tissue and can't learn to kill any TCRs that match.
Maybe we'll combat this in the future by finding a way to donate or genetically engineer a whole bone from the organ donor, thus having bone marrow matching the donated organ. If we could get localized immune suppression on only those parts, that would be cool. I guess those leukocytes would be attacked immediately.
It amazes me how much 'tech' is always running on a cellular/molecular level.
https://www.youtube.com/watch?v=SMtWvDbfHLo (DNA transcription)
https://www.youtube.com/watch?v=TfYf_rPWUdY (mRNA translation)
https://www.youtube.com/watch?v=I9ArIJWYZHI (DNA replication)
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.
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.
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).
FYI: WAG stands for Wild Ass Guess. They usually don't involve citations.
*The interview discusses the material in Katherine Eban's book Bottle of Lies.
It is nothing more than rank speculation that these two stories are somehow related. The world is teeming with junk science like this, and it can be dangerous and even fatal. (E.g. anti-vexers). That's why I think it's important to recognize it when you see it, and call it out. Even more-so if you find yourself possibly espousing damaging speculation without a scintilla of evidence.
Before dismissing my comments out of hand maybe you should look at my evidence.
He didn't claim that your evidence was faulty, but that there is nothing to connect these two stories. You're making a link that does not exist.
In fact, when you say
> It is possible that this is not what happened
you are making it seem quite likely that this is indeed what happened. With no supporting evidence.
It's exactly what anti-vaxers do.
“I had such a low quality of life prior to my face transplant. Do I wish it had lasted 10 or 20 years? Of course,” she said.
I was on an email list and a woman who had two lung transplants described some of what she had been through and also asserted she would do it again and had no regrets.
You have to understand these are people who have no other viable options. However bad this is, the alternative is worse.
I wrestle with these questions because I wish we were looking for better answers. I am in no way interested in telling people who have had transplants that they were wrong to choose that for themselves.
But transplants are dramatic, heroic, headline grabbing procedures. Helping people keep their organs functioning so they don't need a transplant has much less capacity to grab headlines and fascinate the public and so on.
We increasingly put our time and effort into really dramatic medical procedures that are very expensive and have a golly, gee whiz factor. I think we are likely largely overlooking better paths that would give a higher quality of life in many cases because they have less razzle dazzle.
I'm periodically shocked when I'm reminded of how wide is the spectrum between good and bad.
Are there pictures?
I am just left speechless, there really should be a death penalty for intentionally maiming a person to the point that they will live the rest of their life in suffering and sorrow. No one deserves the fate this woman has been left with. I am sorry she will have to endure another transplant.
Not trying to 1-up you but I can't imagine how anyone could do this to anyone.
Edit: to those curious what happened to the husband. 30 to 70-year sentence (age 52 at the time), died in prison. https://www.vnews.com/Man-Convicted-of-Maiming-Vermont-Woman...
I don't think empathy and punishment are at odds with each other. It's perfectly possible (and, I think, healthy) to have deep compassion for both victims and perpetrators, while still taking the right corrective measures.
Depending on what exactly "stringing up" entails, I might be right there with you.
“I have fully forgiven him and I don’t have the same attitude that a lot of people have with his treatment of me,” Tarleton said. “I have moved on so well and in so many ways. I feel like, for me, it ends a big chapter in my life.”
More than what happened to her, what stands out to me is that she's moved on. That's strength. There are things that no one can take away.
In most cases, no, the people trying to bleed you emotionally with their pity party for you aren't going to do a damn thing to help improve your quality of life. They will only add to your suffering.
Shutting them down as efficiently as possible as just part of protecting yourself from yet more damage in a cold, cruel world full of assholes.
Self-blame is very common in victims of domestic abuse, and when one suffers from it they're predisposed towards "forgiveness". It's really a compensation for feeling somehow responsible for their own abuse, which is very unfortunate.
I'm glad she seems to have found some closure in his death though.
If anyone hasn't been through some tragic medical shit in their life, pay attention to that. You'll understand it later.
It won't teach the perpetrator not to commit the same crime again. Malice only breeds malice.
If it is deterrence, you're too late as the act has already been done; you may argue that it might stop others from committing it, but since this was a deeply irrational crime reasonable consequences didn't factor into it.
Making the victim feel better? Seeing their attacker hurt may seem cathartic on a visceral level but it won't undo the damage.
Making you feel better? That wouldn't be justice, that'd be sadism.
Torturing criminals to "make them feel the same pain" is a visceral response that brings brief gratification, but it's not a solution to anything.
So the judgment on whatever should happen in case where guilt is really not in doubt must be reserved for omniscient infallible divine beings, as we the people simply are not capable of implementing a process that's able to determine when guilt is not in doubt, as all practical experience shows that we've tried and failed and failed and failed to do so.
Rehabilitation is just as important, if not more so, than punishment. Simply locking someone in a cage for a few years does nothing to prevent recidivism. It often makes it worse, as once someone comes out of prison, it can be extremely difficult to find work (since employers discriminate against felons), causing them to turn back to a life of crime in order to survive.