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

by Matt Richtel

Another big daddy of a plague was the Black Death, a killer of millions of people, including, at one point, as much as half the world’s population in the fourteenth century. The Smithsonian magazine describes three different ways the plague attacks: through the skin, attacking lymph nodes (bubonic); through the blood; through the lungs. The deadly nature of the plague owed to several mutations in the bacteria that made it elusive to the immune system and easy to transfer. Our immune system, in the case of the lung version, was virtually helpless.

Black Death (14th Century) Bubonic one type

And a quick but important word about the bird flu that scared the living daylights out of infectious disease specialists in 1997. A three-year-old boy died in Hong Kong, and then seventeen

Bird Flu 1997

There is a key aspect to that flu that is consistent with other deadly viruses. The people who died weren’t overcome by the flu itself but by their immune system’s response to the flu. The immune system went into hyperdrive to stop what it perceived as an extraordinary foe. Massive inflammation followed. “It was a cytokine storm,” Dr. Fukuda said. “People were dying from having an overwhelming response.”

Cytokine storm

“AIDS was the 9/11 of immunology,” a developmental

In 1984, 3,454 people died of AIDS. It was going to get much worse. More than four times that amount would die four years later, and then the disease exploded globally.

the highest level, there are two ways to understand and stop the spread of a pathogen like a flu virus or HIV. One path is to examine the chemistry, the biology, and the response of the immune system—the antibodies, the hard science. The other is to look at the circumstances surrounding a disease or outbreak, the epidemiology.

1 of 2 ways to stop spread. Environment.

Remember that a virus hides in cells. That can make it very hard to detect, even with sophisticated tests. The virus does slip out of cells as it goes from one to the next, but if you don’t know what you’re hunting for, “it’s like looking for a needle in a haystack,” as Dr. Fauci said.

Virus behavior

Understanding the retrovirus requires the slightest explanation of basic genetics. DNA is the biological master plan. It dictates an organism’s characteristics and traits. RNA helps execute the plan. I think of DNA as the architectural blueprint, and the RNA is the general contractor. RNA puts the plan into action, and it instructs lots of “subcontractors,” like cells and proteins. A retrovirus adds a new and unexpected twist.

He was the first to discover a retrovirus in human beings. It was called human T-lymphotropic virus type I. HTLV. This is a retrovirus that infects T cells. We understand much more about it now than was grasped then. We know now that the virus is

There were 16,908 deaths related to AIDS in 1987, according to the New York Times, 20,786 in 1988, 27,409 in 1989, and 31,120 in 1990.

Protease is the enzyme in HIV that helps the virus mature once it leaves the nucleus of the cell it has infected. If the enzyme gets inhibited, the virus doesn’t mature. The virus doesn’t spread. The immune

Deaths globally in 1998 were 2.5 million, the most in any year, and the total dead from the epidemic was just shy of 14 million. The disease continued to be focused in developed nations but was increasingly spreading to emerging countries, with 70 percent of the people infected that year in sub-Saharan Africa, UNAIDS reported.

Bob was cautioned that he could still die if his immune system faced another assault—from, say, hepatitis, shingles—another debilitating attack that required his immune system’s full attention.

Many so-called elite controllers, patients like Bob who keep HIV at bay, have a gene that impacts the way the immune system recognizes foreign invaders. Specifically, they share a genetic variant called HLA-B57. HLA stands for human leukocyte antigen.

These are major revelations, particularly the idea that the way you deal with a disease might well be dictated by this idea of a prime, or first point of contact. The initial response, whether to flu or HIV or a cold, might well echo through the immune system. The right first response could save your life, not that you have particular control over such a thing.

protein diet for several weeks at a time, a regimen that was the precursor to the Atkins diet—meat and eggs, her only snack pork rinds, occasional cottage cheese. “My

irritable bowel syndrome. This is a condition that causes a range of stomach disorders—pain, constipation, diarrhea, gas. It is not an autoimmune disorder per se, but it can often involve inflammation, which is caused by an excessive or prolonged immune response. It is a cousin

But it is fair to say that Linda was building a life that was not consistent with her own limits—nor with those of most people’s. She was losing track of what was true and consistent with her, what was her real self. In a certain way, her life was being driven by the pathology of nonstop work, a foreign invasion that was threatening not just her emotional health but also her physical health.

Pathokkgy of nonstopl work. Forein invasion threatens physical & mental healfth.

For as prevalent as autoimmunity is, its diagnosis can be worse than tricky. For a long time, the condition was invisible.

lupus to it. The word derives from the Latin word meaning wolf.

typically impacting the joints. Remember that inflammation is the body’s own response to disease. Inflammation is not “other.” It is “self.”

You might know Compound E by a different name, cortisol. Cortisol is a steroid that suppresses the immune system. Steroids are the first line of defense

As in so much of immunology, other major pieces began to fall into place in the late 1950s, as scientific technology improved. For instance, lupus researchers could now see that the condition involved a patient’s own immune cells eating away at free-floating material in the bone marrow.

antibodies—those large specialized molecules on cell surfaces that help our bodies target what to attack.

hear the intimate medical and personal narratives of two autoimmune sufferers, Linda and Merredith—two of the stories I share in this book. Their stories also provide insight into some of the key factors that impact the balance of everyone’s immune system—namely, sleep, stress, hygiene, family history, and the ecosystem of our gut, known

“the baby’s protection from disease is pretty much exclusively from the mother’s immune system antibodies.”

when the baby is born, whereas the man might’ve flown the coop. A caregiver might need higher protection from disease. Women generally have more body fat than men, so perhaps they have more immune system cells, Dr. Hahn postulated to me. She also noted that many of the genes that are associated with lupus and rheumatoid arthritis are on the X chromosome. (Women have two X chromosomes, whereas men have one X and one Y.)

So the math of autoimmunity became greatly weighted toward females. (Another piece of science trivia: When researchers want to create an antibody to study, they use a female animal, not a male. You get more antibodies.)

downside of a strong immune system, then, is that it can become more susceptible to being inflamed or set off by lack of sleep or stress or—this will likely go without saying—genetics. Fifty percent or more of cases appear to have a distinct genetic link, with a family member having had the condition, or a related one. Another factor that can

prednisone. Dr. Lambert described it as “being like a big hammer. It shuts a lot of things down.” It’s used to treat many inflammatory diseases. “But unfortunately it has all this spin-off all over

In November 1998, the U.S. Food and Drug Administration approved one of most anticipated drugs in medical history: Enbrel. It was aimed at treating rheumatoid arthritis. What was so widely

suffering from ulcerative colitis and Guillain-Barré syndrome, a rare and nasty disorder. Here, our elegant defense, the immune system, turns against the lining that coats the ends of long nerve cells that extend along the periphery of the body. The linings of the nerves, known as myelin sheaths, are crucial because they help the body to quickly and efficiently transmit information by insulating these cells and, in effect, keeping out other information. In Merredith’s mother, though, T cells and B cells had begun to cooperate in attacking the myelin sheaths. “Guillain-Barré is called a syndrome rather than a disease because it is not clear that a specific disease-causing agent is involved.

Merredith’s

she knew of Merredith’s regular experiences