Thursday, April 2, 2020

Immune ‘Boosters’ Ignore the Immune System’s Best Quality: Balance

When I got sick as a kid, my father would draw a cartoon of the battle my immune system was fighting in my body. He would sketch an antibody man, shaped like the letter Y, with bulging muscular arms, getting ready to beat up an angry-faced bacteria or virus.

As I grew older, I've noticed that we all cling to these metaphors of physical violence when talking about the immune system. Immune cells called phagocytes devour trespassing bacteria. "Killer" T-cells destroy cells that have been hijacked by viruses. It's ingrained in how we explain the complex system within ourselves that protects us from foreign invaders.

In a 2016 essay in Aeon about the militaristic language we use for the immune system, science writer Jon Turney described a children's book from the 90s called Cell Wars, about "a brave band of cells that keep you healthy by constantly battling against all kinds of invading germs. Every minute, every hour, every day of your life, they are fighting.”

“The imagery of war is hard to get away from,” Turney wrote. Earlier this month, New York's governor, Andrew Cuomo, said of the COVID-19 pandemic, "This is a war. We have to treat it like a war."

Simultaneously, my inbox is teeming with pitches for products that claim they can "boost" my immune system. As a novel coronavirus infects hundreds of thousands of people all over the world, these ads prey on the desire to bolster our troops, give them more ammunition—to go to war. Supplements, juices, soups, elixirs, broths: they all promise to get my immune system into fighting shape for its inevitable showdown with a new enemy.

But this conception of the immune system isn't entirely correct. It does protect us from invading cells, but the system at large is not a cannon set on autopilot. What's more important to the immune system than all-out war is balance. An immune system that is overly-"boosted" is not desirable, but in fact, deadly.

A timely illustration of this is one of the leading causes of death among people with COVID-19, the illness caused by the new coronavirus. It's an extreme overreaction of the immune system, called a cytokine storm. This storm is a thunderous, devastating, often fatal burst of immune overactivity. In these cases, it is not the virus that directly kills a person, but their immune system. There is discussion among clinicians about a treatment for COVID-19 patients that wouldn't "boost" the immune system but instead, turn it down.



A healthy immune system is not fighting every minute. It's also deciding what not to react to, what not to kill; this discernment is a skill it spends our whole lives refining. The immune system's job, said Petter Brodin, an immunologist at the Karolinska Institute in Sweden, is to maintain a healthy relationship with all of the bugs that live in, on, and around us.

If the immune system killed everything foreign in sight, we would not have a microbiome (the millions of beneficial bacteria that live in and on us), and our bodies would resemble "scorched earth," said writer and journalist Matt Richtel, the author of An Elegant Defense: The Extraordinary New Science of the Immune System.

“It’s all about balance and timing,” Brodin said. “The immune system is an exquisitely well-balanced system. But if someone has an allergic reaction, they can be dead in half a minute or seconds. What does that tell you? It tells you the immense power that the immune system has. It can kill you within seconds, but it usually doesn’t because it’s well-regulated.”

I've found myself thinking about the immune system and cytokine storms, and about the upset balance between overreaction and underreaction, as we observe government and individual missteps in reaction to the pandemic. We could stand to learn some lessons from our own immune systems—about how we mount a defense, decide when to act and when to lay low, and how we define ourselves versus what's "foreign."

The immune system is complicated. It employs a vast network of cells and tissues to continuously scan the body for trouble. We are born with innate immunity, which is our body’s ability to fend off invading cells from the get go. And throughout our lives, our body’s learned immune response, the adaptive immune system, steps in. Each time we get an infection or a vaccination, our immune system learns, and can protect us from that pathogen if we encounter it again.

To do this, the body recognizes things that don’t belong, called antigens. Antigens are proteins on the surfaces of bacteria, fungi, or viruses. A longstanding conception of the immune system is that its job—summarized in just a few words—is to detect cells that are not "us."

In the 1949 book, The Production of Antibodies, scientists Frank MacFarlane Burnet and Frank Fenner introduced this notion that the "self" was inextricably tied to the immune system. Burnet thought that the self was actually defined by the immune system, since it decided what the "non-self" was that needed to be attacked. Just like there are borders around countries that define its residents, our body was the border that contained our cells. Any other "not-self" cells that crossed those borders needed to be killed.

We know now that it's more nuanced than this. All around us, every day, microbes lurk. They’re on our bodies, computers, clothes, food, and, yes, doorknobs. Any one of them could be your body’s foe. But many of them are also your body's friends. Others are microbes that care little about you at all.

With the discovery of the microbiome, we've come to realize that our immune system frequently leaves the microbes in our bodies alone, even though they are not human cells, technically are not the “self.” At other times, the immune system even persuades them to colonize us. Take one antibody protein called IgA, for example, after it recognizes the antigens on some gut bacteria. "Does that signal their destruction?" Turney wrote in the Aeon essay. "No." Instead, when IgA binds to the bacteria, it helps it take root in our guts, establishing a new home there.

Cytokine storms are one example of how too much immune reactivity isn't ideal. When the novel coronavirus enters the body, the immune system senses it. It releases inflammatory cells, called cytokines, which enlist other immune cells to help. This process should be controlled and regulated, but in some patients with COVID-19, it starts to boil over: The lungs are flooded with immune cells trying to fight the virus and clear away damage. But they start to build up, kill healthy tissues, and damage other organs. It leads to an inability to breathe as fluid floods the lungs, drowning a person on dry land, while their organs fail.

Getting your immune system to hulk out on turmeric or vitamin C—even if that did work—isn’t the desired end goal.

Immune imbalance can lead to other problems, too: autoimmune disorders, when the body attacks cells that it’s not meant to, or food allergies, when the immune system reacts too strongly to a foreign substance. This is why the notion of “immune boosting” doesn’t make sense, Richtel said. Getting your immune system to hulk out on turmeric or vitamin C—even if that did work—isn’t the desired end goal.

Richtel said before he wrote his book on the immune system, “I thought it was some combination of forcefield and nuclear device,” he said. “I was wrong.” A healthy immune system is not only made up of molecules that are “killers” but also ones that tell cells to stop, pause, and withdraw. He now commonly describes it as a love child between a ballet dancer and a bouncer: A powerful offensive force, but one that’s held in check; an entity that is gracefully checking IDs at the door.

In the early weeks of the coronavirus pandemic in the U.S., some people under-reacted. They continued to go on spring break, they didn't commit to social distancing, they didn't close up their businesses or schools. Others over-reacted. They hoarded food, toilet paper, masks, and hand sanitizer. Both types of imbalance threaten our communities, the “body” we all live in.

People have attributed blame to nationalities that are outside of our borders—as if the delineations we've created somehow matter to a virus that spreads indiscriminately. They've "spit on, yelled at, attacked" those who look like the people who live where the virus first came from, as if this would somehow enact violence against the virus itself, instead of damaging parts of their own communities.

Our desire to boost the immune system, to make it strong, is in line with these other imbalanced reactions. People reach for these products to try and recreate some sense of control. We are scared. We can’t see the immune system, nor can we see this virus; we can only feel their residual effects. Buying or eating something that allegedly offers protection feels like an ounce of power in the face of a huge global disaster that grows worse by the day. But instead we need to make choices in a balanced way that helps the entire organism we’re a part of.

There are ways to help your immune system maintain balance. “There are two sources of enormous control,” Richtel said. “They are wonderful and for some, daunting, because they are habits and not magic pills. People want agency, but they also want it cheap. In this case, it does come cheap and easy but it requires some discipline. The two things to do are: lower stress and increase sleep.”

Stress interferes with the immune system by way of a primitive mechanism. In early human life, when faced with danger, adrenaline kicked us into fight-or-flight mode. Research suggests that during these moments, resources get shifted from our immune system to our need to survive—to run faster when we’re being chased by a predator, for instance. Our bodies produce chemicals like epinephrine, cortisol, and norepinephrine, which help to power through stressful moments like those, but also impede our immune response. Today, we're not running from tigers, but our bodies still respond to stress in the same way.

In the early weeks of the coronavirus pandemic in the U.S., some people under-reacted. Others over-reacted. Both types of imbalance threaten our communities, the “body” we all live in.

If you don’t get enough sleep, you never get a break from your adrenal hormones, Richtel said. Research has shown this affects your immune system in many ways too, lowering the number of certain immune cells, while increasing other inflammatory cells at the same time.

Richtel's advice—to sleep more and stress less—reminds me of how most of us are being asked to do something extremely simple and yet incredibly hard: stay inside. The most "balanced" response—the one that will help us as individual systems and as a societal system—is to not go out. Wait and rest.

This is not something that fits with the militaristic idea of the immune system. The metaphors around our immune system make us want to be active, to put on our armor and fight. But if we try to muscle our way through a pandemic, go back to work, fight with brute force—it won’t end well for us or for others.

This shift from defense to balance also leads to a more complicated idea of the self. Before, it was simple: I am me, and there are things out there that aren’t me. My body protects me against those things that aren’t me. There was an easy boundary between the self and the other. But now, with the immune system as a wise gatekeeper, I've come to realize: I’m not only me. There are a lot of things in me that aren’t me. There's a complicated system that’s making choices based on my environment, what I’ve done, what I’ve eaten, where I’ve lived, who I’ve loved, who my parents are. Sometimes that system messes up.

The delineation between ourselves and foreign invaders starts to break down as we recognize that our immune systems allow many other organisms to pass through us and live with us to help us thrive. Can the separation between our individual needs and wants and what will help other humans follow? If we start to think of the way we protect our "self" as being less of a war and more of a communal practice of balance, it might help us take the actions needed during this pandemic to protect the organism that is our collective human community.

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