An Elegant Defense: The Extraordinary New Science of the Immune System: A Tale in Four Lives

by Matt Richtel

Along the way, we humans learned to take steps to bolster our defenses. Prior to the discovery of medicines, we developed all manner of custom and habit to support our survival. In this way, think of the brain—the organ that helps us develop habits and customs—as another facet of the immune system.

Ritual washing gets mentioned in Exodus, one of the earliest books in the Bible: “So they shall wash their hands and their feet, so they will not die.”

The immune system responds to our environment and learns. This is central to the branch of the immune system known as the adaptive immune system. Our immune system comes into contact with various threats, develops an immune response, and then is much more able to deal with that threat in the future.

To survive, we adapted within our physical capacities. We washed our hands, swept our floors, cooked our food, or avoided certain foods altogether. We learned and adapted. Then our learning and adaptation began to intensify as we built quickly upon past discoveries. Human discoveries came in leaps and bounds. We developed medicines like vaccines and antibiotics. Virtually overnight, we changed the environment with which our immune system interacted.

On one level, we had given a major helping hand to our immune system. Its enemies list was attenuated. On another level, though, our immune system is proving that it cannot keep up with this change.

At a core level, we have created a mismatch between our immune system—one of the longest surviving and most refined balancing acts in the world—and our environment.

The percentage of children in the United States with a food allergy rose 50 percent between 1997–1999 and 2009–2011, according to the Centers for Disease Control and Prevention.

But have our diagnoses improved?

In keeping with the themes mentioned earlier in this chapter, food and respiratory allergies rose with income level. More money, which typically correlates with higher education, meant more risk of allergy. This could reflect differences in who reports such allergies but also differences in environment.

More likely former than latter

This is not to say that all of these increases are due to better hygiene, a drop in childhood infection, and its association with wealth and education. There have been many changes to our environment, including new pollutants. There are absolutely genetic factors as well. But the hygiene hypothesis—and when it comes to allergy, the inverse relationship between industrialized processes and health—prevails.

One powerful clue the researchers discovered was that the households of the Amish were much more likely to have allergens, “from cats, dogs, house-dust mites, and cockroaches.” Forty percent of Amish homes had them, compared to 10 percent for the Hutterites.

starting in the late 1980s, the market for such hygiene products—home and personal—surged 81 percent. The authors cite “return of public concern for protection against infectious disease,” and it’s hard not to think of AIDS as part of that attention.

Bacteria are passing back and forth among themselves a genetic code that allows them to fend off attacks from antibiotics. In fact, bacteria that are under attack from antibiotics can effectively call out to their fellow bacteria for help (“Send me some protective genetic material!”) and the resistance can be transferred.

you and I are 99.9 percent similar in our underlying genetic building blocks. But the microbiome—the underlying genetic material of the bacteria in our gut or hand—can differ by 80 to 90 percent. (Worth noting is that most bacteria are in your gut, though there are also 500 bacterial species in your mouth, and about the same number in your “airways”—the respiratory system; 300 million are on the skin; for women, about 150 million are in the genital infrastructure.)

Mazmanian and others have since found that the gel that lines the gut is colonized by the microbiota, and their presence puts them very much in close proximity to cells that can trigger an immune response. On the other side of that gel-like wall is a line of cells, called epithelial cells, that is heavy with immune triggers. This suggests the microbiota have developed with the deliberate ability to interact with and stimulate our immune system.

Imagine if you were at war all the time with your neighbors; you’d eventually kill each other off, as surely as the Hatfields and the McCoys. Instead we find common ground, cooperate, and maybe get some help with coexistence by setting up fences and boundaries.

In the grand scheme, these pathogens are a tiny fraction of the bacteria in the world. For the bacteria we cooperate with, our microbiota, these pathogens become a common enemy because our body is the host where the microbiota lives.

Each of us develops a working relationship with our environment. It’s a social contract of sorts with the bacteria in our midst, and the contract is highly personalized and highly variable.

In mice, babies who live in the same cage with their mothers have microbiota more similar to their mothers than do babies of the same mother who are caged elsewhere.

One of the many variations of T cells, we now know, is called a T regulatory cell, or Treg. It is a powerful subset of our T cells that has been shown, among its other roles, to help suppress the immune system.

Treg cells are not so unusual. What makes them worthy of note here is that there is a decent chance they wouldn’t exist without the presence of the microbiome in the gut.

Treg cells don’t get developed when certain gut bacteria are missing. In other words, when the microbiome of the mouse is incomplete, so is the immune system.

“There are entire cell types in the body that don’t exist because the DNA doesn’t have all the information to tell that cell to develop,” he said. It’s not just Treg cells, but natural killer cells and other killer immune cells that appear to be triggered by the bacteria.

There is a powerful punch line to Mazmanian’s work: The way we relate to bacteria in the world dictates our health. If the relationship gets out of whack, our immune system becomes unbalanced too.

Mazmanian jokes that the toilet is a mixed blessing, compared to pooping in the woods: half burying the bacteria, half washing our hands.

So it’s not that we want to do away with many modern amenities and be surrounded by bacteria. But it is true, Mazmanian says he has since learned, that the result of overly cleansing our environment and using antimicrobial soaps and wipes is to limit the microbiota we pass back and forth among us.

Some of us are colonized with certain types of bacteria while others of us carry different ones. Throughout human history, we have passed these back and forth, shared them, creating a vast trading network through handshakes, hugs, and cheek pats, shared use of stair banisters or countertops, and on and on. Now we kill our microbiome instead of sharing it.

We have reached an inflection point at which our relationship with bacteria is fundamentally shifting. Bacteria are organisms we share this planet with, and with which we have coexisted for millennia. The relationship is changing because we as a species are fighting to survive and bacteria are fighting to survive.

in the case of our relationship to bacteria, we control only half the equation. We can try to take steps to put less pressure on bacteria, but we can’t ultimately dictate how these powerful organisms will react.

When the cadets entered, roughly 30 percent lacked the antibody for Epstein-Barr virus. They had essentially not encountered it in any meaningful way. Of that group that had the antibody, 20 percent eventually “became infected,” according to the research paper, written by Yale scholars and published in 1979 in Psychosomatic Medicine. Among the cadets who became infected, 25 percent not only had antibodies but showed clinical signs of being sick. What was surprising was one common thread among cadets likely to develop infectious mono: They were doing poorly in school, had highly accomplished fathers, and were themselves particularly motivated to succeed.

Sometimes when a pathogen is detected but the pathogen appears not to be spreading and not to be too dangerous, our elegant defenses watch and observe—acting more like peacekeepers than assassins. Herpes is a wonderful example.

Sometimes, though, when the immune system gets preoccupied, stressed, or tamped down, it provides an opening for the virus to emerge. Herpes, sensing this temporary weakness, travels down the nerve roots into the mouth and attacks. Now the Festival of Life is under attack and the immune system must respond in force.

During exams, there was a sharp fall in the number of natural killer cells that circulated outside the bone marrow.

The stress of exams was suppressing a key part of the immune system. Why might this be? During exams, there is a surge of adrenaline. This precedes the release of steroids.

steroids help to maintain the integrity of blood vessels; in times of stress, when the blood vessels might constrict, these steroids keep them intact and, without putting too fine a point on it, maintain your blood circulation and pressure so you don’t faint and die.

Virtually every cell has a receptor for these types of steroids, and that receptor is called a glucocorticoid receptor. When the steroids become active or elevated, they can reach many, many cells—“every cell in the body,” according to Dr. Jonathan Ashwell, an expert in cell biology at the NIH. It’s a remarkable idea in and of itself. In the giant festival, this hormone courses through the entire confines of the party and has an impact on the behavior of many, many partygoers. At least the ones that are self.