In the traditional view of your immune system, your body is a fortress that needs to be defended. You trust your immune system to be constantly on alert for enemies like harmful bacteria and viruses, and to be able to fight them off when they attack. But Prof. Philip Calder, Professor of Nutritional Immunology at the University of Southampton (UK) and the latest winner of the Danone International Prize for Nutrition, says although this is an important part of what the immune system does, our thinking needs an update. In his work, Calder emphasizes that the function of the immune system is actually much broader: it ensures we respond appropriately when we encounter any pieces of the world around us—small or big, harmless or harmful.

“The immune system was first discovered because of its association with infections and pathogens. That has to be the primary purpose of the immune response,” Calder says in a phone interview with GMFH. “In addition to that, the immune system and the immune response makes sure that we can live happily in an environment which is actually quite threatening to us. Every day you will be eating probably thousands of plant and animal [substances called antigens], for example. And you live happily with those because your immune system recognizes them but makes a decision that they’re not threatening in any way.”

Calder says, on one hand, a well-functioning immune system must have a strong enough response when stimulated by a foreign (non-human) substance. “A resilient response would be a response which deals effectively and efficiently with the source of the immune stimulation—that is, the elimination of the bacteria or viruses—in a way which doesn’t cause excessive damage or illness to the host.”

On the other hand, he says, a resilient immune system is one that can also maintain a passive response. “The immune system is, all the time, having a less active response to things which are not threatening,” he says. But if that system breaks down, he notes, it could potentially lead to immune-mediated diseases such as allergy or arthritis.

So how would someone without disease know when their immune system has the capacity to face everything that comes its way? Says Calder, “Inflammation is part of the immune response. What we want is [for] inflammation to happen when inflammation is necessary.”

From this point of view, immune system resilience is about more than avoiding sickness. It’s about maintaining an inflammation response that is neither too passive nor too active, 24/7. “A resilient response is really a response which is in the right place at the right time, following the right path, and controlled. If you lose that resilience, then some sort of disease happens,” says Calder, adding, “It’s quite a fine balance between having a good response and not.”


Gut microbiota affect immune response

Calder notes that the activities of the gut microbiota are important to take into account when talking about immune response. “There is a series of mechanisms by which the microbiota interacts with the host immune response. Those mechanisms are still being investigated,” he says. “[But probably] the nature of the microbiota could influence the nature of the host immune response.”

“The different microorganisms, particularly the bacteria within the gut lumen, are producing chemicals that act on the host. Some of those… interact with the immune cells,” Calder explains. These chemicals include, for example, the short-chain fatty acids (SCFAs) that are produced when bacteria in the gut consume non-digestible fibre for humans: SCFAs interact with the gut-associated immune system, an organized set of immune cells located under the gut lining.

These findings support the idea that the gut microbiota could potentially be modified to fine-tune the immune response. “Because nutrition particularly affects the gut microbiota, there could be an indirect route between nutrition, the gut microbiota, and the host immune response,” Calder says.

The second article in this 2-part series covers the role of nutrition in building a resilient immune system.