As far as gravity is concerned, spaceflight can be divided into two components. You’re exposed to hypergravity during launch and landing. Most of the time in between those events, there is microgravity. Researchers led by Katherine Taylor of the University of California Davis and her colleagues used some space-faring flies (Drosophila) to figure out how our immune systems might be compromised by those changes in gravity.
Flies have two major responses to infection, one (Toll) that is used primarily to fight off fungi, and the other (Imd) for bacteria. Mammals have similar immune pathways, which is why flies are a good model organism.
The researchers infected flies with a fungus and then simulated hypergravity by putting the flies in a centrifuge, essentially fast-spinning wheel like the kind used to train astronauts. Interestingly, the spinning flies were more able to fight off the fungi than their sedentary neighbors. For some reason, their Toll systems seemed to be improved over flies not exposed to hypergravity.
Testing the effects of microgravity was less simple. For that, the researchers used a population of flies that had been reared entirely on board the shuttle Discovery (now resting at the Smithsonian National Air and Space Museum) during one of its missions. Upon arriving on Earth, the space flies had severely compromised Toll systems. In contrast the flies’ Imd pathway seemed to be intact. They were just as capable of dealing with bacterial infection as their Earth-reared cohorts, but terrible at fighting off fungi.
Many genes involved in all sorts of processes from metabolism to metamorphosis were over-expressed in the Space flies and a few others were under-expressed. In particular, the production of proteins associated with the stress response was altered. Some of these changes could have resulted in the immune effects.
It’s not clear why hypergravity would have one effect and microgravity the opposite effect on the flies. Human space missions spend a tiny percentage of their time exposed to hypergravity compared to the time at microgravity. Hopefully, the problems of microgravity will be solved for the next generation of astronauts.
By the way, if you're worried about Chris Hadfield, he's adjusting to life back on Earth just fine.