From what I understand, random interactions with wild pathogens can prime the immune system in the wrong way, leading it down the wrong path. This is why some people can get lucky with immunity and be super resistant to flu, because they happened to luck into a response that targets a common factor in most flu strains. Other people have bad luck and target some area that mutates frequently, and they proceed to get walloped by every flu strain, every year.

This is why it's hard to make a 'super vaccine' for flu, becuase it takes many rounds of shots to retrain some people's immune systems once they've latched on to the wrong recipe for antibodies.