The year an individual was born plays an important role in determining his or her susceptibility to a given strain of influenza, a new study reveals. The results provide clarity around a long-standing question surrounding flu susceptibility; that is, why are infections with one strain, H5N1, found mainly in children and young adults, whereas H7N9 cases mostly affect older individuals? Recent experiments have revealed that broadly protective immune responses can provide cross-immunity between different flu subtypes. Flu viruses are categorized into two groups. Group 1 consists of subtypes H1, H2, and avian H5, whereas group 2 contains seasonal H3 and avian H7. Katelyn Gostic et al. hypothesized that individuals exposed to infection by a virus from one of these groups subsequently experience a reduced risk of severe disease from novel strains within that same group. Indeed, they found that the year a person was born - and thus, which flu strains they were exposed to during childhood - strongly influenced their future susceptibility to various flu strains. For example, individuals born before 1968 likely experienced their first flu infection from a group 1 virus; those individuals appear protected against viruses of the same group, including H5N1. Conversely, initial infection with group 2 viruses, often the case for those born after 1968, appears to protect against the group 2 virus H7N9. The protective effects of being exposed to either strain were profound, reducing the risk of severe infection with H5N1 or H7N9 by about 75%, and the risk of death by about 80%. The authors speculate that this cross-immunity occurs due to antibodies that target the stem of the hemagglutinin protein found along the surface of the virus, noting that this stem has remained fairly unchanged across subtypes, whereas the head of this protein has mutated substantially across strains. A Perspective by Cécile Viboud and Suzanne L. Epstein provides more context.