In the last few thousand years, AfroEuroAsian civilization experienced a large amount of urbanization and population density increases.
This resulted in diseases that cross over from other species to have a fertile ground to spread and infect in waves that cross and recross the world. Many millions if not billions die over the generations, those that survive adapt to being resistant to the kind of symptoms the disease generates, and the disease adapts to be more efficient at spreading.
When AfroEuroAsian explorers reached isolated communities who hadn't been exposed to the huge host of diseases they where used to, the diseases did a clean-field burn of the populations. Fewer diseases came back, as the volume (time times area) of dense human habitation wasn't as large; but possibly not absent. It is possible that syphilis did transfer back from the Americas.
The seed population of Astronauts would have a genetic pool from the surivors of such pandemics. They would also carry with them aquired immunity to common earthborn diseases; that, however, lasts at most a generation or two, and sometimes as little as a decade or less.
Their innate response to infection might not drift rapidly. That innate response is mostly what makes you die or not die to a given disease. A disease, say smallpox, might kill 1/3 of people who where culled by a previous smallpox epidemic in their genetic history, while kill 90% of those who lack that culling.
There would be some drift. Back on Earth, new diseases and variants would spread, and those whose innate immune response was fatal would die and tend not to pass on their genes. The red queen's race would continue.
Those on the station would have their innate immune response mostly drift, or respond to variations in the small number of diseases they carry with them. Immune systems that overreact to sterile environments with massive allergies might be selected against, for example. But if your immune response to the common cold (which dies out in a small population) in the next generation is massive and debilitiating, you wouldn't even notice.
There is also the possibility of a pandemic hitting Earth, killing a significant percentage of the population. Such a hit would result in those with an immune response that isn't fatal to that disease being selected-for. Multiple such pandemics could cause significant genetic drift over the entire Earth.
So these different factors would result in the innate immune response of the Space Fairing and Earth populations diverging. The Space Fairing would also experience the founder effect and larger amounts of drift due to smaller population size, where quirky unique mutations in the founders might end up being extremely common, or later mutations doing the same.
Over 7-10 years, your immunity to colds and flu would fade. Going back, you would be likely to get a really bad cold and possibly flu, which could be fatal. The next generation would get some antibodies from their mother via breast feeding, but their immune system would mostly be missing defences agianst common earth infections; so they would risk a really, really nasty lung/ear/eye/skin infections when they come back. This would increase over time. These can be fatal, but they aren't like 90% death rates with modern medicine.
The multi-generation effect of genetic drift and the red queen's race back on Earth could result in the isolated population having mass deaths. How long this would take is extremely hard to guess, as we haven't really had a good experiment. Even Pitcarn island was only isolated for 20-odd years.
Animal models aren't any good, because we are stange critters with our city-hives, worldwide travel, and quirky immune systems.