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Kindle Notes & Highlights
by
Matt Richtel
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January 26 - January 31, 2021
20 percent of the American population, or 50 million Americans, develops an autoimmune disorder.
The immune system story is one of life and death, of course, a story of survival under the deadliest conditions. As much as that, it is about the struggle for peace and harmony, for successful integration, immigration of organisms across body and border, manifest destiny, and evolution. It is a story of friendship.
What we can see clearly now is that arthritis sufferers, people with celiac disease or lupus, even people who suffer seemingly mysterious bouts of fatigue, fever, and pain, all share an often-invisible threat: an elegant defense that is out of balance, an immune system that has overcompensated, been triggered to act without proper constraint.
Survival depends on knowing what is self and what is alien. The immune system must cope with three major challenges: the variability of bad actors, the central circulatory system that sends rivers of blood throughout our body in seconds, and the need to heal.
The B cells came from bone marrow and generated antibodies. The T cells matured in the thymus and could either fight or direct action. They are generals and soldiers.
Antibiotics are arguably more important than vaccines. In fact they are “probably the most successful forms of chemotherapy in the history of medicine.
Studies have shown the MHC gene gives off a scent. The scent is used as a factor in how people choose their mates. If one person’s MHC is too similar to another’s, the MHC will act as a repellent. The scent of MHC that is sufficiently different will act as a magnet. This is significant from several perspectives. For one, it shows the unconscious drive for a certain level of diversity, given that diverse couplings provide to offspring a broader set of abilities.
“Inflammation is—very generally speaking—the body’s immune system’s response to stimulus.”
Consider for a moment the profundity of that question. There had long been an assumption that fever was linked to infection. In contrast, what Dr. Dinarello was pursuing was the idea that infection need not be present, and that, in a manner similar to the case of the woman with lupus he’d witnessed in medical school, the body was generating the fever with its own molecule, without necessarily being prompted from the outside.
cytokine is a secretion from a cell that prompts action by other immune cells. It is a messenger. It can be sent by an interferon or any of a number of other immune system actors.
The T cells, when alerted by dendritic cells, behave as soldiers and generals, spitting out cytokines; the B cells use antibodies to connect to antigens as if they are keys in search of a lock. Macrophages, neutrophils, and natural killer cells roam the body, tasting and exploring, killing. These networks get connected by signals, chemical transmissions, or processes; are spurred on by interferon and interleukin; and can induce powerful side effects, like fever.
Dinarello likes the analogy that the immune system has turned the body into a police state. “You need inflammation to protect against invaders. You need policemen. But if police get too rambunctious, they cause damage and kill innocent people.”
At its core, what the immune system was doing wasn’t simply seeking and destroying. Instead it was looking for a balance—between attacking and neutralizing real dangers and showing sufficient restraint such that its potency didn’t destroy the body. In 1980, Dr. Fauci helped capture this pivot in immunology by naming a new lab at the NIH. He called it the Laboratory of Immunoregulation.
Mark the moment. The story of the immune system became the story of homeostasis—a state of harmony or stability.
He didn’t mean that the immune system was having a new effect, but rather that it was now clear to scientists how powerful the effect was everywhere. “Cancer, autoimmunity, auto-deficiency, allergy.”
The thing about autoimmunity is that the questions and answers sometimes don’t get any further than focusing on the symptoms. My joints ache, I have fever, I’ve got this rash, I have diarrhea, constipation, mind-numbing fatigue.
And the doctor says: I believe you, but I can’t find anything wrong. Something is wrong, all right. But there is nothing to point to. There is no pathogen. There is no infection. There is no foreign disease. No aspect of the immune system story is as pointed or pure as that of autoimmunity.
Even to this day, autoimmunity remains one of the most challenging conditions in medicine to diagnose with precision.
The Johns Hopkins University School of Medicine divides the materials of the diagnosing of autoimmunity into three categories that collectively sound like types of evidence at a criminal trial. The evidence can be direct, indirect, or circumstantial.
Women live longer, and they tend to be the last to die in, say, a famine or in an epidemic. The exact reasons aren’t known, but Dr. Hahn offers some theories as to why, in an evolutionary sense, women might have a stronger immune system. One possibility is that women confer the first immunity to their babies.
This "stronger immune system" is what, theoretically, may explain why autoimmune disorders affect women disproportionately to men. Females have a more active/overreactive immune response. Fascinating!
Another theory, she offers, “is that women tend to be caregivers.” Women, by definition, are there 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.
Biological evolution's really out here trying to keep the (female) nurturers alive. And all by *potentially* giving them more immune system cells! Cool beans.
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.)
Makes sense then that women tend to be afflicted by RA and lupus at higher rates than men, no?
In the end, though, Dr. Lemon conceded that Merredith is a classic example of something she sees all the time with autoimmunity. “We listen to their stories and we try to fit them into the box, but millions of people don’t fit into a box. They’re not making up what they’re experiencing, they’re not flakes. We just don’t know what’s wrong yet.” For these people, Dr. Lemon said, “science has not caught up yet.”
This underscores the complexity and uniqueness of every person's genome.
People who don’t sleep are more likely to develop heart disease, cancer, and depression. “We now have compelling evidence that, in addition to cognitive impairment, sleep loss is associated with a wide range of detrimental consequences, with tremendous public-health ramifications,”
Read "Why We Sleep" by Matthew Walker if you want more elaborate information on the harm acute/chronic sleep deprivation can do to your body. It is WILD. You will never want to miss out on 7 hours of sleep again.
One interesting bit of medical industry trivia arises here as well. When you see a drug with mab on the end, you now know it stands for monoclonal antibody.
A little bit of medical trivia I'm going to tuck away in my back pocket, thank you.
These neurons aren’t the lion’s share of the brain. A lot of the volume of the brain is consumed by a set of cells called the glia—comprising 80 percent of the brain, Dr. Barres told me. Broadly, glia are non-neuronal cells. These glia are central to the immune function of the brain. The glia come in three flavors: astrocytes, oligodendrocytes, and microglia.
Because of the blood/brain barrier, scientists thought, for a long time, that immunity didn't exist in the brain. Enter: the glia cells. These babies may end up revolutionizing modern medicine and our treatment/understanding of inflammatory disease as we know it!
