There’s a joke about immunology, which Jessica Metcalf of Princeton recently told me. An immunologist and a cardiologist are kidnapped. The kidnappers threaten to shoot one of them, but promise to spare whoever has made the greater contribution to humanity. The cardiologist says, “Well, I’ve identified drugs that have saved the lives of millions of people.” Impressed, the kidnappers turn to the immunologist. “What have you done?” they ask. The immunologist says, “The thing is, the immune system is very complicated …” And the cardiologist says, “Just shoot me now.”
The thing is, the immune system is very complicated. Arguably the most complex part of the human body outside the brain, it’s an absurdly intricate network of cells and molecules that protect us from dangerous viruses and other microbes. These components summon, amplify, rile, calm, and transform one another: Picture a thousand Rube Goldberg machines, some of which are aggressively smashing things to pieces. Now imagine that their components are labeled with what looks like a string of highly secure passwords: CD8+, IL-1β, IFN-γ. Immunology confuses even biology professors who aren’t immunologists—hence Metcalf’s joke.
Even the word immunity creates confusion. When immunologists use it, they simply mean that the immune system has responded to a pathogen—for example, by producing antibodies or mustering defensive cells. When everyone else uses the term, they mean (and hope) that they are protected from infection—that they are immune. But, annoyingly, an immune response doesn’t necessarily provide immunity in this colloquial sense. It all depends on how effective, numerous, and durable those antibodies and cells are.
Immunity, then, is usually a matter of degrees, not absolutes. And it lies at the heart of many of the COVID-19 pandemic’s biggest questions. Why do some people become extremely ill and others don’t? Can infected people ever be sickened by the same virus again? How will the pandemic play out over the next months and years? Will vaccination work?
To answer these questions, we must first understand how the immune system reacts to SARS-CoV-2 coronavirus. Which is unfortunate because, you see, the immune system is very complicated.
It works, roughly, like this.
The first of three phases involves detecting a threat, summoning help, and launching the counterattack. It begins as soon as a virus drifts into your airways, and infiltrates the cells that line them.
When cells sense molecules common to pathogens and uncommon to humans, they produce proteins called cytokines. Some act like alarms, summoning and activating a diverse squad of white blood cells that go to town on the intruding viruses—swallowing and digesting them, bombarding them with destructive chemicals, and releasing yet more cytokines. Some also directly prevent viruses from reproducing (and are delightfully called interferons). These aggressive acts lead to inflammation. Redness, heat, swelling, soreness—these are all signs of the immune system working as intended. [Continue reading…]