How hard the flu hits us has a lot to do with our first experience of the disease, a new paper reports.

Researchers at the University of California Los Angeles (UCLA) and the University of Arizona may finally have an explanation as to why different people seem to have such different reactions to the flu. And, to a large extent, they report, it has to do with your childhood.

Early experience

“Our immune system often struggles to recognize and defend against closely related strains of seasonal flu, even though these are essentially the genetic sisters and brothers of strains that circulated just a few years ago,” said lead author Katelyn Gostic, currently a postdoctoral fellow at the University of Chicago.

“This is perplexing because our research on bird flu shows that deep in our immune memory, we have some ability to recognize and defend against the distantly related, genetic third cousins of the strains we saw as children.

An individual’s ability to fight off the flu is related to the number of different flu strains they contracted during their lifetime and the order in which they did so. Prior exposure to a pathogen, be it in the wild or controlled (in a vaccine) is known as immunological imprinting.

For the study, the team set out to determine whether immunological imprinting could explain differences in how people respond to the flu. They used health records from the rizona Department of Health Services to track how different varieties of the virus affect people at various ages, focusing on the H3N2 and H1N1 strains. These strains were selected as both have led to seasonal outbreaks over the past few decades, so there was enough data on them to work from.

In very broad lines, H3N2 is more closely associated with severe flu cases in elderly people and causes the majority of flu-related deaths. H1N1 seems more partial to children and young adults and is far less deadly.

The data showed that people who were first exposed to H1N1 during childhood were less likely to require hospitalization if they re-encountered the strain later on in life compared to those who were first infected with H3N2. Similarly, this latter group would be more resistant to subsequent reinfections of H3N2.

The team looked at the evolutionary relationship between the two strains and report that they belong to two different branches of the influenza family. Further research revealed that while infection with any of the strains does somewhat boost resistance against any other, the best effects are seen with strains from the same family that an individual has battled before. Furthermore, your first exposure seems to grant you extra protection against related strains in the future: people who had their first run-in with flu as children in 1955 (N1H1 strain) were significantly more likely to be hospitalized with an H3N2 infection than an H1N1 infection when both strains were circulating.

However, the team also found that people whose first childhood exposure was to H2N2 did not have better protection when they later encountered H1N1 (although the two strains are closely related). They are still unsure as to why this is.

“We hope that by studying differences in immunity against bird flus — where our immune system shows a natural ability to deploy broadly effective protection — and against seasonal flus — where our immune system seems to have bigger blind spots — we can uncover clues useful to universal influenza vaccine development.”

The paper “Childhood immune imprinting to influenza A shapes birth year-specific risk during seasonal H1N1 and H3N2 epidemics” has been published in the journal PLOS Pathogens.