The Dynamics of Immunity

The strength of the immune system’s response to respiratory infections is constantly changing. According to a Francis Crick Institute study published today in Nature Immunology, the immune response is even influenced by an organism’s history of previous unrelated infections.

There are two types of immunity: adaptive and innate. Adaptive immunity provides immune “memory,” allowing a fast and strong immunological response when the same disease is encountered more than once. In contrast, innate immunity provides a broad and less-specific first line of defense against all pathogens that is vital to control infections the body has not experienced previously.

The new study found that after recovery from a respiratory infection, particular cells in the innate immune system in the lung are more effective, offering extra protection against new infections in the following weeks. Specifically, they found that mice given the flu virus were significantly less likely to catch a completely different bacterial infection a month later.

This heightened immunity is the result of how, during the initial infection, a particular type of immune cell travels from the bone marrow to the lungs and turns into a lung macrophage. Once in the lungs, these cells produce cytokines, which are hormone-like molecules that cause inflammation and help fight pathogens. These macrophages remain in a more reactive state in the lungs after the infection is resolved, offering an extra layer of protection from future infections over the following weeks.

However, over time, the ability of these macrophages to produce high levels of cytokines disappears. This means that, after a couple of months, protection against infection decreases and eventually returns to the same level as in animals that had not previously been infected. The researchers believe this mechanism could also be true for humans.

“Flu is a serious disease, especially for vulnerable groups, and we’re not suggesting that a flu infection is desirable,” says first author Helena Aegerter. “Rather, this research provides valuable insights into how a viral infection that is cleared quickly can continue to affect immunity for weeks afterwards, through long-term changes in innate immune cells. This could partially explain why our response to diseases can vary; what you could fight off with no symptoms one week could have nasty effects a couple of weeks later.”

The researchers plan to look further into how a history of infection affects the immune system, including in conditions such as asthma or chronic obstructive pulmonary disease, in which the heightened inflammatory response could worsen symptoms.