How long would human immunity last in space?
I won't claim to be a biologist, but I'm fairly certain that it's really hard for disease to survive in space because most bacteria and viruses need a host in order to survive for long periods of time.
So, let's say a group of very healthy astronauts were sent out into space. Their only contact is with one another and they reproduce. Their children wouldn't come in contact with many childhood diseases, and while they may inherit some antibodies from their parents, their immune systems would probably take a slight hit after not needing to fight off any of these diseases.
I'm assuming that some diseases that were on the ship at take off would mutate in order to survive, but the vast majority of human illnesses will never make it on board.
How long will it take for the immune systems of this group of people (and their descendants) to deteriorate so that they can't return to Earth without dire effects to their health? Would this even be an issue?
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I'd suggest that they may lose at least partial immunity to a decent extent within a decade or two of leaving Earth.
According to Smith et al. (2014) (explained for us laypeople here), the number of disease outbreaks has been rapidly increasing over the last few decades:
Specifically, there's been a large increase in bacteria- and virus- carried infections.
I'd argue that this could be quite a problem. Immunity to past strains of a disease can be created through vaccinations, and I see no reason to not bring enough on the ship for future generations. There's no sense in having a child somehow get chicken pox when they go to Earth just because someone felt it wasn't worth sending an extra syringe along.
The odds of this are extremely low, assuming proper procedures are followed to make sure that no diseases manage to hitch a lift on the ship. But with 3000 outbreaks happening over the span of five years - many likely from new varieties of illnesses - it seems highly likely that the descendants will not be prepared to deal with any of them once they leave space. The only way out would be to constantly supply the ship with vaccines from the latest strains of disease, or to ensure that the spacefarers undergo quarantine when they come back until they receive the correct vaccinations - not bad, considering the odds of them contracting, say, Ebola while in Earth orbit are slim to none.
So, without vaccinations in space or back on the ground at arrival, I'd say that within ten years or so, they'd be incapable of dealing with a variety of new strains - many minor, some significantly worse - when they go to Earth.
I'm aware that the question asks for "dire effects". Diseases which can have nearly guaranteed severely negative effects on most members of a population don't necessarily follow the same trends as shown above and can be difficult to anticipate in advance. If a disease that becomes the next smallpox strikes Earth within ten years, this answer becomes very different. But if we don't see such an epidemic within a few decades, then the answer is simply that there won't be any significant problems.
I don't think I'm qualified to speculate on when the next pandemic will hit, so I'm not going to try.
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