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Kindle Notes & Highlights
by
Matt Richtel
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March 21 - April 1, 2020
In 1952, as Time magazine reported, the worst outbreak yet infected 58,000 Americans, killing 3,000 and paralyzing 21,000. “Parents were haunted by the stories of children stricken suddenly by the telltale cramps and fever,”
An individual’s elegant defense didn’t care simply about the infection; it cared about the infection when it attacked its own personal habitat. Italicized because it’s a key scientific insight.
These T cells are often considered the equivalent of hit men.
major histocompatibility complex, or MHC—another immunological term that goes down
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.
Relatedly, it also creates the possibility that the immune system originated not just to keep us away from pathogens but also to help us choose mates that are sufficiently self but not too much. In fact, the MHC could be part of the reason that incest has evolved to be so abhorrent.
As humans developed, he told me, “We had to make sure we did not kill ourselves by homogenizing.
Most people have a body temperature within a relatively restricted range, roughly 97 to 99 degrees Fahrenheit for adults and slightly elevated for children, 98 to 100.4, give or take.
Avg body temp range: adults & kids
Interestingly, body temperature was at its peak at around six P.M. each day.
When we experience a fever, we become tired and develop chills. We feel it all over, a very powerful neurological response.
“Inflammation is—very generally speaking—the body’s immune system’s response to stimulus.”
inflammation is the reaction of the body to an event that challenges our well-being.
Another example of an everyday inflammatory response is the one set off by the common cold. It often is caused by a rhinovirus, which makes a battleground of your nose. The virus replicates there. The blood cells in the area open up to allow for easier access by immune cells. They flood in. Swelling! The vessels become permeable, allowing more flow of fluid. Leaking! Your stuffy nose explained.
The technical term for one cell eating another is phagocytosis. That word derives from the Greek word phageîn, which means to eat. So the macrophages are big (macro) eaters. These cells are like the love child of a janitor and a cop who eats first and asks questions later. They attack cells in the region that might be damaged or infected by consuming them and then chemically blitzing the devoured particles. These macrophages derive from and are a subset of a broad group of immune cells known as monocytes. Some monocytes turn into macrophages. But others take on a very different function.
In fact, T cells and B cells, together known as lymphocytes, make up only as much as 40 percent of the white blood cells. The monocytes comprise 5 percent, give or take.
The biggest chunk is made up of cells known as neutrophils. They are both spies and assassins.
In the Festival of Life, neutrophils are first responders. “If you scrape your
The macrophage comes soon thereafter,” said Dr. Anthony Fauci, whom I mentioned earlier, the director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, and one of the most influential contemporary scientists.
In the 1970s an experiment involved yet another immune cell—the natural killer. The discovery is interesting in and of itself, and also because it was part of the broader reframing of the understanding of the immune infrastructure. The scientific narrative had been about the primacy of the T cell and the B cell. That narrative was falling apart.
Pus, it turns out, is the detritus of neutrophils, the cells that rush into action at the first sign of insult. They kill what is around them and die in the process. When you observe pus oozing from your body, you’re seeing these dead cells. The 1943 paper posited that the fire was sparked
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
And it came from a monocyte, one of those immune cells like the macrophage (which devours refuse and pathogen), but one that now appeared to have much broader function.
Dr. Dinarello called it a leukocytic pyrogen—a fire starter born of the white blood cells, the leukocytes. “He realized, ‘Oh my god, it’s not coming from the neutrophil. It’s coming from the monocyte,’” recalled Dr. Fauci, who worked with Dr. Dinarello on the eleventh floor. When Dr. Fauci related the story to me, his own voice rose with elation. His excitement took a moment for me, an outsider, to appreciate, given how thick these conversations are with immunology speak. But
The assembled, having accepted the notion, decided to give a new name to these so-called mediators. Henceforth, a leukocytic pyrogen would be known as an interleukin. Inter from a root for “means of communication.” Leuk from the Greek root for white, as in leukocyte (white blood
At the most basic level, it meant that the interleukin-1 was inducing not just fever but also a T cell response.
The deadened virus had interfered with the development of the live virus. Hence the name: interferon (IFN).
entailed using a natural substance to fight disease. The alternative, building medicines around foreign substances,
Or consider the horror of chemotherapy, in which terrible toxins attack tumors but at the cost of scorching self.
Eventually researchers would identify three types of interferon: alpha (A), beta (B), and gamma (G), and then much later, lambda (L).
The thing is, the immune system has multiple overlapping, sometimes redundant first lines of defense, and second lines too. This festival—our take-all-comers cocktail party—is nothing if not chaotic and multifaceted.
“When interferon is secreted, you feel sick. It causes aches and pains; you feel terrible,” Zoon explained. Your behavior is being modified—not by the virus directly, but by the response. In
Tired, sore, hot, as I described earlier. You are slowed down, and this can have the very beneficial impact of diverting your body’s resources to fighting the virus and not, say, focusing on your job or going for a jog. Your defense system needs your limited energy.
Interferon belongs to a broader set of chemicals that prompts immune system action. This set of chemicals informs virtually all of disease, including how we respond to it. Meet the cytokines.
A 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 thymus makes T cells. The bone marrow is the origin of B Cells. They flow in the tunnels and vessels that make up the lymphatic system and congregate in lymph nodes and lymphatic tissue. These are like command centers, surveillance hubs where the firefighters are awaiting a call. 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,
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.
Conceptually, this is the kind of cascade that keeps you healthy. The system goes after parasites and viruses, bacteria and malignancies. It works nonstop, picking up minor threats that we never experience on a conscious level, and midlevel threats that send us to bed, and myriad major threats that might well kill us absent the presence ...
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The problem with these interleukins is that they can become too abundant, their signals too aggressive. That leads the body to attack with too much ferocity. This is called autoimmunity. Even
Autoimmunity
The year was 1980, and Dr. Fauci was a rising star, eventually one of the brightest lights in immunology. Since 1972, he’d been on a quest to figure out how to deal with what he calls “aberrant” immune system responses. He meant situations in which the immune system attacks the body.
The story of the immune system became the story of homeostasis—a state of harmony or stability. This is what makes our defense so elegant. It is a system precisely and delicately tailored to stay in balance, keep the peace, and do as little damage as possible to us and our surroundings. This balance is central to our health, as you’ll
Cancer cells grow and grow. They are the body’s weeds.
They are changing your life, right now. Drugs built on monoclonal antibodies have become a dominant source of drugs in the early part of the twenty-first century. The annual market for these drugs is nearly $100 billion. They work by intensifying—or dulling, as the case may be—the performance of a particular antibody so that the body does a better job of attacking a life-threatening risk, like cancer,
chemotherapy and immunotherapy. In traditional chemotherapy, toxins that destroyed fast-dividing cells got dumped into the body, ideally killing, say, a lung tumor, but taking out lots of healthy tissue as well. This was the proverbial war of attrition. The Festival of Life had to outlive the tumor and the treatment. With nivolumab or ipilimumab, as you’ll see, the idea is to use molecular tinkering to unleash the immune system to attack cancer—using the body’s natural defenses—rather than injecting bleach into the body and killing everything that moves.
This was the discovery of what happens at first contact. The Toll-like receptor is as elemental a concept as in all of our survival and in the science of immunology,
The discovery became the basis for our understanding of the concept of a second kind of immunity. It is called innate immunity.
To break the findings down further: We are born with primitive detection mechanisms that can discern not only what is alien but what is pathogen. As a first-line defense, the molecules of the innate immune system recognize a large class of pathogens and signal the T cells: That thing you just identified as alien is bad—go kill it.
“The CDC defines a case of AIDS as a disease, at least moderately predictive of a defect in cell-mediated immunity, occurring in a person with no known cause for diminished resistance to that disease.” To repeat: occurring in a person with no known cause for diminished resistance to that disease.
The 1918 flu pandemic killed up to 50 million people worldwide, according to the Centers for Disease Control, nearly 700,000 in the United States.
But one important theory is that what made it so deadly is that the flu virus in humans—to which we’d adapted some immunity—had combined with a genetic variant from birds. What this meant was that many human beings did not have an antibody to combat the flu, even among the massive pantheon of antibodies we all get born with. This is what the CDC says: “Influenza experts believe that a pandemic is most likely to be caused by an influenza subtype to which there is little, or no, preexisting immunity in the human population. There is evidence that some residual immunity to the 1918 virus, or a
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1918 Flu Pandemic
