Effects of stasis on adaptive immunity

Factual Questions
1

My understanding is that immune systems and pathogens are in a constant Red Queen’s race against each other — pathogens are constantly evolving to get past immune system defenses, and adaptive immune systems are constantly adapting to those changes by exposure.

If I’ve got that wrong, feel free to correct me. But if I’m correct so far, then imagine that someone is in stasis for 20 years. (For my purposes, I mean that by some magic or sci-fi voodoo, their body is “frozen” and isolated and doesn’t change at all for 20 years.) When they come out of stasis, their immune system hasn’t changed at all — but the pathogens in the outside world have. Their immune system is now 20 years behind on that race.

Would this have a noticeable effect on their adaptive immunity? Would they get sick more easily? Would mild illnesses like the common cold affect them worse because the virus is potentially very different from what their body is used to? In other words, would they be, for all intents and purposes, immunocompromised? Or is my reasoning totally off and it wouldn’t matter? (For instance, maybe their innate immunity would be enough to pick up the slack.)

If I’m right and they would be effectively immunocompromised, how bad would it be? For instance, what if they caught a cold? What about a more serious virus?

2

There is not one single population of germs, nor one single population of humans, and 20 years is too short for thorough mixing of either. At the absolute outside, your person coming out of 20 years of stasis would be no worse off than someone visiting a foreign country.

3

I know all of these things. I’m not clear on how that supports your conclusion. What am I missing?

4

Twenty years is too short a time. For the most part, hundreds or thousands of years is needed and even that would only be in exceptional circumstances. When the Europeans arrived in the New World, they brought with them dozens of diseases that were new. Many were deadly, but it’s thought that smallpox played the largest role in decimating the population.

Unless that someone had the misfortune to sleep through a deadly disease striking the rest of humanity, the immune system would be approximately as good as anyone else’s.

5

Human defenses nowadays are not exactly the same now as they were 20 years ago, and germs are not exactly the same now as they were 20 years ago. But by the same token, human defenses are not exactly the same in the US and Europe, and germs are not exactly the same in the US and Europe. The only way that the defenses a European person has can spread to the American population is for a European person to come here and have children and grandchildren and so on, and that takes a lot more than 20 years. So the difference between immune systems in the US and Europe must be a lot larger than the difference across 20 years.

6

The Red Queen Hypothesis usually refers to evolution. A single organism does not evolve, evolution is something that happens to a population, it takes place across multiple generations within a population through differential rates of survival and procreation among organisms with different traits. Organisms that by chance are less susceptible to pathogens will tend to survive and have more offspring, and the trait may eventually spread throughout the population. So the Red Queen Hypothesis is not really applicable to your scenario.

What’s applicable for one organism over 20 years is the question of exposure to new pathogens, through which we gain immunity to repeat infection, immunological memory. The first thing you’d want to do when waking up is get your vaccinations up to date. But for unvaccinated conditions, if you wouldn’t have died 20 years ago upon first exposure there’s no obvious reason why you’d die today on first exposure - other than the fact that you’re older and less robust. I suppose that simultaneous first infections might be slightly more likely if you’re in a dangerous part of the world. But most of us don’t usually have frequent encounters with life-threatening pathogens that we haven’t been vaccinated against.

7

Let me modify slightly what I wrote.

Individual organisms do not evolve, so your immune system will not be fundamentally any better or worse after 20 years with or without stasis. Any difference would be in your immunological memory - the question of whether you had a first exposure to something during those 20 years that granted you immunity to repeat infection, similar to the process of vaccination.

In most cases, I think you would be no less capable of fighting off a first infection after your hypothetical 20 years in “stasis”. However, 20 years is plenty of time for a pathogen to evolve, since microorganisms have a short generation time. So it’s possible that more dangerous forms of some pathogens might have evolved in that time. And if you had not been in stasis, it’s conceivable that you might have been exposed to a first infection from an earlier less dangerous form of that pathogen, survived that first infection, and gained immunological memory that grants you immunity to the new more dangerous form too. Whereas a first infection from the more dangerous form might not be survivable.

But I’m searching for rare scenarios here - in general I think it’s unlikely that it would make any difference at all, you wouldn’t need to sequestrate yourself from humanity.

8

This is actually a pretty unlikely scenario, which probably explains your inability to find an example. In general, pathogens evolve to be less dangerous, since their host dying is not good for the microorganism, either individually or as a population.

9

First, note that evolution is not a vicious arms race- it’s more a matter of “whatever works”. Smallpox remained smallpox because it killed about 10% of the population, and the rest gained immunity. Therefore, there was no great selection for a more deadly disease - the same disease could come back in a generation and the result would be the same. It was more of a steady state. In fact, a disease more deadly to the host runs out of hosts. (Just as preadators usually don’t kill off all the prey, the situation evolves into a steady state. And there was no tendency for the hosts to evolve built in immunity, because they already gained immunity after exposure if they survived.

Flu virus and HIV are two examples of viruses that mutate much more easily - but again, flu rarely kills off the host unless they were already weak. I wonder with HIV if we haven’t seen the same effect (and maybe with bubonic plague centuries earlier). the more lethal varieties kill off the hosts before they spread far, the less lethal has more time to spread because the host does not die as soon and exposes the virus to more possible hosts, so diseases become less lethal over time. The first major flu epidemic killed huge numbers of people in 1919, but subsequent ones have been fairly mild by comparison.

I read a review, many years ago, of a book about the last great smallpox epidemics in northwest North America and Alaska. Poring over records and memoirs, the author contended that the smallpox was no more lethal to natives than Europeans. It wiped out entire villages because everyone became sick at once - in a subsistence economy, there was nobody left to fetch food and water for the sick, people died of exposure and dehydration while feverish. Sometimes one or two in the village managed to survive anyway. In villages with someone previously expose who was immune - a missionary, or a villager who had been to the big city and suffered through - the death rate was often not any worse that the 10% mortality rate Europeans experienced because someone could tend to the sick. But that is the key - people can survive a major fever because someone nurses them while they are sick, covers them, prevents dehydration, provides food once they can eat. Left unattended in a huddle on the floor or out in the open, death rates are far higher.

So it’s likely that a person frozen for decades or centuries might encounter a disease that nobody of his or her time had encountered, but odds are the familiar diseases have entered a steady state where they co-exist and would pose no greater threat.

10

Yes I agree. I probably should not have bothered to add my second comment above, I was trying to imagine rare scenarios that might happen.

The succinct answer to the OPs question is - no, you would not get sick more easily, provided you got up to date with your vaccinations.

The principal reason being the (common) misconception about how evolution works. Individual organisms do not evolve, populations evolve. So the Red Queen Hypothesis does not mean that individual organisms change throughout their lifetime.

11

I actually wasn’t necessarily thinking of the pathogen being inherently more dangerous, but simply different from what the subject’s immune system has been exposed to before — sufficiently different that maybe it can’t respond very effectively.

I know, that was the crux of my scenario. Their immune system hasn’t changed at all.

There we go — that’s what I was wondering about.

This is pretty much the exact scenario I was picturing. But from what everyone’s saying, it sounds like it’s very unlikely. Okay, fair enough. Thanks. :slight_smile:

Sorry, I didn’t think to mention that in my scenario this person most likely can’t update their vaccinations after the stasis. They might be able to get a few, but they won’t be able to get all the recommended ones. They might not be able to get any at all. Does that make a difference? (I assume not, but I’ll ask anyway.)

I didn’t think it meant that, and I don’t think I said anything that would suggest I did. But no matter — thanks for your help! (That goes for everyone else, too. Thanks!)

12

Your first two paragraphs are not clear on the distinction between two rather different things.

The Red Queen Hypothesis is about the evolution of the immune system. Evolution by natural selection means that adaptive traits proliferate in a population. And as noted, evolution does not mean that individual organisms change, it means that the frequency of heritable traits in a population changes.

One of the adaptive traits that has evolved in the human lineage is the adaptive immune system. But these two uses of the word “adaptive” refer to completely different things.

In a discussion of evolution, an adaptive trait is a heritable trait that imbues an organism with evolutionary fitness - i.e. survival & reproductive success. Through natural selection, an adaptive trait will tend to become more common in a population. Over time, it may become fixed in a population - all organisms may possess the trait. But again to reemphasize - this does not come about by any organism changing. It comes about through organisms that possess the trait having more offspring than organisms that do not; fixation means that organisms that do not possess the trait ultimately have no descendants at all.

The adaptive immune system is the part of the immune system that reacts (“adapts” in a more usual colloquial sense, not the evolutionary sense) to specific pathogens. After initial exposure, immunological memory triggers a much more rapid response to any subsequent re-infection with the same or similar pathogens. So rapid that you probably won’t know anything happened. This is the part of the immune system that makes vaccination so remarkably effective.

13

I guess the point to make is that some organisms change easily and frequently, some remain the same -roughly.

Let’s consider smallpox. It has a target audience - humans not yet exposed. For these, it seems to attack easily. Then, as the discussion above touches on, the body’s adaptive response means the host is immune form then on. So will smallpox change much? That depends. It’s found an express vector into human bodies; will a small change make it more infectious? Bypass the immune response of previously exposed hosts, so it can infect again? For smallpox that does not seem to have been the case. In fact, smallpox vaccine was discovered by the observation that a less dangerous cowpox conferred the same immunity (trained the adaptive response against the same virus surface molecules?) without the disfigurement or high risk of death. So unless the mutated virus wins the trifecta - bypass immune response to cause infection again while retaining the same infectious capability and being significantly lethal - it is not going to be a “better disease”. The current one seems to be good. A “better” disease that doesn’t spread fast is not much of a threat.

This is the crux of evolutionary niches - highly specialized organisms are adapted to a specific set of environmental circumstances, and once there, it’s difficult to escape. It’s the simple, more generalist organisms that are the cornerstone of the next wave of complex, differently adapted organisms. (Mammals came from mousey little things, not adapting from raptors and T-Rex.)

The flu might be a differently adapted virus. it’s included in its toolchest a surface that can change sufficiently to fool the adaptive immune system by reconfiguring into an unrecognized shape that the herd has far less immunity to. But, along with this it is far less lethal, and is a bit more difficult to spread. unlike smallpox or bubonic plague, it does not spread like wildfire and infect every host, nor does it kill most. This to would be an appropriate adaption - flu can give partial immunity to other varieties, so something that spreads too fast will tend to create a better herd immunity for any related variants. (despite what people call colds, many people have not had the real flu - it’s usually a lot more severe than a bad cold, I hear).

And as Reimann points out, the human body is not changing it’s immune system - it’s the same old immune system, just creating new antibodies - but only in response to infections. The fact that except for the regular warnings about new flu strains, we really don’t have massive outbreaks of untreatable and llethal diseases - that should tell you that the “arms race” model is not entirely correct. Things are nt changing that fast.

There is the occasional trifecta. Smallpox, whenever it emerged. Bubonic plague. Spanish flu. There’s the suggestion that syphilis was imported by the Spanish from the new world, and found an opportunistic vector in a more dense and mobile society in Europe.

14

Pathogens have a vastly shorter generation time than humans, giving them a huge advantage in an evolutionary arms race. The way we have adapted to resist this is really interesting. Our immune system effectively “encrypts” antigens, with the encryption key contained in the Major Histocompatibility Complex. This makes it much more difficult for pathogens to hide by evolving to resemble molecules that are naturally present in the human body, since it’s the encrypted form of antigens that’s presented to T-cells for judgment; and the MHC is highly polymorphic, meaning that a human population contains a wide selection of different “encryption keys”.

There’s quite a bit in this thread about this and other aspects of how the adaptive immune system works.
http://boards.straightdope.com/sdmb/showthread.php?p=19830766

15

But then, from that thread, it sounds like the process the adaptive immune system goes through really is a sort of microcosm of evolution: Try mutations for everything, then keep the things that work.

16

Yes, there’s an analogy in the sense that we don’t “intelligently design” an antibody or T-cell receptor to recognize something, we generate a huge diversity of random specificities and then select those with useful specificity. Of course, the random mutation to generate diversity is tightly regulated. The primary process is V(D)J recombination, which involves massive mutation of a specific segment of DNA at a particular time in early development. Later there’s another process called affinity maturation that involves further generations of random mutation and selection.