Everyone gets sick. Despite all the vegetables we eat or vitamins we gulp down, sooner or later pathogens such as viruses and harmful bacteria infiltrate our bodies, and we need to take a time-out. We sit back and let our immune system do its job.
But when it comes to getting sick, not all immune systems are equal. Some people seem to get sick much more often than others. One could easily conclude that these individuals—such as elementary school teachers or hospital workers—are merely exposed to sick people more often. But susceptibility to illness isn’t as simple as the odds of being exposed to someone with a cold. Each person gets sick differently.
Moreover people recover differently. Not everyone returns to their baseline level of health after the flu or COVID. The biology behind why and how some people get sick more often than others is still largely unknown. But a paper published on June 13 in Nature Communications shines a light on the components of immune resilience—the ability to restore immune functions that stave off diseases and control inflammation caused by infectious diseases, as well as other sources of inflammation.
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Scientific American spoke with the study’s lead author, Sunil Ahuja, a professor of medicine at the University of Texas Health Science Center at San Antonio and director of the Department of Veterans Affairs Center for Personalized Medicine, about why some people fall ill more often.
[An edited transcript of the interview follows.]
Why are some people more susceptible to getting sick?
In general, one would consider three main factors. One would be genetic susceptibility: you’re born with a genetic predisposition to becoming infected more easily. You could have inborn errors, such as polymorphisms in genes that are well described for host immunity.
Second would be environments where there’s a heavy burden of infection. If you look at our ancestors, a lot of them passed away by the time they were in their 50s because they had a greater antigenic load [the amount of inflammatory stress an infection causes] before there were vaccines, higher living standards and better sanitation.
These are kind of static factors. But then the third factor is response to inflammatory stress. I might respond in one way to one infection and in another way to a different infection. It’s a yin-yang. Environment plays a role, and that same genetic thing that’s protective against one infection can be detrimental for another infection. People show variation in how they respond to these challenges—which could also have a genetic basis. When we respond to challenges, we all have what I would call “a burst of inflammation.” We all need some inflammation, but it has to be the right amount at the right place at the right time. The injured or infected site gets swollen, red and warm. These signs of inflammation at that site are saying, “Help, I need white blood cells to show up at that site to ward off further spread of this inflammation and to allow for healing.” The body produces these chemical substances, which we now call chemokines. “Chemo” stands for “chemoattractant”—it’s the attractant for white blood cells.
There are people who can be hyperinflamed and hypoinflamed. People vary in their amount of inflammation. In our study, being able to control inflammation and preserve immunocompetence was associated with being asymptomatic. Some people are infected yet don’t get sick because they had a really good inflammatory response.
It seems that people in some professions, such as teachers, get sick more often. Why is that?
One reason is in part related to the microbial load. You’re taking 30 or 40 kids into close quarters. It’s exposure. Not everyone will get sick. It’s a subgroup of these people. This susceptibility is population-based, not individual-based. If I took a group of day care workers, they have so much exposure to respiratory viruses, influenza, and so on. The greater the exposure, the greater the likelihood there will be some degradation.
I told you about inflammation and how it can increase or decrease an effective immune response. We go through such cycles repeatedly in our life. There will be some people who, despite these repeated cycles, manage to preserve that resilience piece; there will be some people whose response is moderately degraded; and there will be some people who have this susceptibility at any age to degrade—that’s what we call nonoptimal.
The traditional way of doing research is to compare the old versus the young. This presumes that the only thing that is different between a young person and an old person is their age when, in fact, that’s not quite true. One might need to break down the old group into varying degrees of immune health. That’d be like saying, “I’m in my 60s”—which I am—“and I’m now an old fart, and I’m like every other old fart.” That may not be true. There are old farts who are 110 years old who do just fine.
As a whole, a group may be at greater risk of getting infections, but that risk is largely localized to those people with eroded immune health. Among that group is a subset who are susceptible to degraded immune resilience—that is, among people of a similar age. We know that as one grows older, one’s immunocompetence declines. So these infections tend to degrade our immune health at any age.
How can immune resilience affect a person’s longevity?
We could categorize people into four groups. People who have high immunocompetence and low inflammation—by definition, the most protected group—live longer. Then you have those with low immunocompetence and high inflammation. These people will, unfortunately, after controlling for age, die sooner than others. Those who have high immunocompetence, which is good, coupled with high inflammation, which is bad, have an intermediate life span. So do those who have low immunocompetence and low inflammation.
I want to give you an example of those cycles, such as in people who have had a natural influenza infection. Temporarily, they turned on so-called mortality-associated biomarkers. Over time, there was a recovery process. We have these injury-repair cycles. If people have too much injury and not enough repair, they will have some residual inflammation. They got hit with influenza, and then, over time, they recovered, but there was a small group who had this residual stuff left behind.
Are there ways to prevent an infection from seriously harming you?
That would be analogous to saying, “Can I be certain that when I go to my grocery store, some idiot does not want to kill me?” So I don’t think so. Some of the fittest people have gotten the flu and passed away. Among people who have good immune health, can I predict a priori that they will do as well during an infection? I cannot predict that. That is the problem. We do know that people, even young people, who have poor immune health don’t do so well after a vaccine. I could advise them that there is a chance that they may not do so well after getting vaccinated because of their immune health score.
I can only tell you ways to possibly prevent exposure risks that could potentially protect you.
How can you reduce your risk of getting exposed to pathogens?
I’m still very pleased when I see older veterans walking into the hospital with a mask on because it tells me they still understand the basic principle that their immune health is poor, or they’ve been informed of it, and they protect themselves.
Your diet and, I suspect, most importantly, exercise also play a role. I suspect that people who maintain regular sustained exercise, not just periodic exercise, are afforded immune benefits. There’s a huge behavioral component to all of this to change human behavior to mitigate risk. I think behavioral change is so difficult.
The two major things that I would focus on are to use commonsense precautions and to address behavioral issues.