If the immune system ran its own version of The Bachelor, antibodies would, hands down, get this season’s final rose.
These Y-shaped molecules have acquired some star-caliber celebrity in the past year, due in no small part to COVID-19. For months, their potentially protective powers have made headlines around the globe; we test for them with abandon, and anxiously await the results. Many people have come to equate antibodies, perhaps not entirely accurately, with near imperviousness to the coronavirus and its effects. Antibodies are, in many ways, the heartthrobs of the immune system—and some 15 months deep into immunological infatuation, the world is still swooning hard.
Frankly, it’s all getting to be a little too much.
Don’t get me wrong: Antibodies have served me well, and thanks to my recent dalliance with the Pfizer vaccine, the anti-coronavirus variety will be receiving an extra dose of my admiration for a good while yet. I am, above all else, eager for the rest of the global population to nab the safeguards they offer, ideally for keeps.
But antibodies are simply not the only immune-system singles worthy of our love. A multitude of cells and molecules are crucial to building a protective immune response against this virus and many others. It’s time we took a break from antibodies, and embarked on a brief Rumspringa with the rest of the body’s great defenders.
What follows isn’t even close to a comprehensive overview of the immune system, because I am not a masochist, and because no one wants to read a 75,000-word story. Instead, I asked a few immunologists to chat with me about some of their favorite immune cells and molecules, and imagine what these disease fighters might be like if they truly were single and ready to mingle.
As it were, everyone needs someone to be their starter bae.
Some good candidates might be found among the members of the innate immune system, a fast-acting fleet of cells that are the first to contend with an infection. (Antibodies belong to another branch, called the adaptive immune system; more on that later.) They’re a lot like adolescent lovers: dogged and earnest, but impulsive and, on occasion, woefully imprecise. Unlike antibodies, which can zero in on specific pathogens, innate immune cells are built to clobber just about anything that doesn’t resemble their human host. Perhaps it’s no surprise that these underdog cells are often forgotten or outright snubbed in conversations about immune protection.
But the all-purpose approach of innate immune cells has its charms. They’ll try anything at least once, and they’re admirably selfless. When pathogens come knocking, innate cells are the first to volunteer to fight, and often the first to die (RIP, neutrophils). Some ambush invading microbes directly, snarfing them down or bathing them with deadly toxins, while others blow up infected cells—tactics reminiscent of guerrilla warfare. Although antibodies take many days to appear, innate cells will immediately be “by your side when you have a problem,” Ashton Trotman-Grant, an immunologist at the University of Toronto, told me.
These acts of martyrdom buy the rest of the immune system time to prepare a more targeted attack. And in many cases, innate immune cells act so quickly and decisively that they can subdue an invasive microbe on their own—a level of self-sufficiency that most other defenders can’t match.
Some innate immune cells are also just plain adorable. Among the fan favorites are macrophages (“big eaters” in Greek), aptly named for their round-boi physique and insatiable appetite. Their goal in life is to chow down for the greater good. “They’ll never make you feel like you’re eating too much, and they’re open to trying new foods,” Juliet Morrison, a virologist and immunologist at UC Riverside, told me. They’re also endearingly unselfish: If a microbe crosses their path, they’ll gobble it up, then belch up bits to wave at adaptive immune cells as a warning of potential danger. It’s a great gift-giving strategy, Morrison said, especially if weird microscopic puke is what makes your heart go pitter-patter.
Dendritic cells have a similar modus operandi. Like macrophages, they specialize in regurgitating gunk for other immune cells. But they are much more social than macrophages, which prefer to gorge and digest in solitude. Dendritic cells are sentinels and gregarious gossips; their primary imperative is to “talk and hang out with other cells,” and they’ll flit from tissue to tissue to do it, David Martinez, an immunologist at the University of North Carolina at Chapel Hill, told me. If you’ve recently caught word of a new and dangerous infection, you probably heard about it from a dendritic cell.
A few weeks ago, Trotman-Grant put together a March Madness–style bracket to choose the “best” immune cell; after a couple of grueling weeks of voting, dendritic cells won. They’re almost certainly the cells you’d want to take to prom. But Trotman-Grant warned that their social-butterfly tendencies could be a double-edged sword: Dendritic cells just aren’t the type to settle down.
Innate immune cells might be convenient dates, for a time. But while they’re great at first impressions, they can also be commitment-phobes, as likely to ghost you as they are to come on strong. (Besides, who wants to date someone who’s always arriving on the early side?)
The real keepers belong to the adaptive branch of the immune system: B cells—the makers of antibodies—and T cells, which, among many other tasks, kill virus-infected cells. Adaptives are slow-moving specialists. They take down microbial invaders that innate cells can’t handle on their own, relying heavily on intel from macrophages, dendritic cells, and other early defenders. They won’t be the first to make a move, but they’re sharp and sophisticated, capable of singling out individual pathogens and zapping them with precision. B and T cells are self-assured enough to know what they want. Unlike innate cells, they’re also capable of remembering the things they’ve encountered before, ensuring that most pathogens can’t trouble the same person twice; that capacity is the conceptual basis of vaccines. “They do a great job at committing things to memory,” Ryan McNamara, a virologist at UNC Chapel Hill, told me. That also means no missed birthdays or anniversaries—and no chance they’ll ever forget that time you were wrong.
If you’re a fan of antibodies, you have B cells to thank: They are the glorious wellsprings whence these molecules hail. (On Mother’s Day, antibodies call their B cells.) Unfortunately, B cells are often overlooked; as living, dividing cells that hide away in tissues, they’re harder to isolate and study than the proteins they produce. But the antibodies they deploy can be powerful enough to quash microbes before they break into cells, potentially halting infections in their tracks. And even after antibodies disappear, B cells persist, ready to produce more.
Martinez stans the B cells he studies. But he’s wary of their romantic potential. B cells, he said, are almost too good at their job, and will compete aggressively among themselves. Their crime-fighting careers consume them, leaving little room for a fulfilling personal life. “I would say B cells are selfish,” he told me. In the cold light of morning, it turns out a lot of them are just self-involved snobs.
T cells play a far more subtle game. Their career choices range from demolishing virus-killed cells to corralling and coordinating other immune cells. As several researchers have pointed out, T cells might be some of the most underappreciated cells in the war against COVID-19, especially when it comes to vaccines. Some evidence even suggests that, in the absence of decent antibodies, T cells can clean up the coronavirus mostly on their own.
Certain T cells are killers. As their name suggests, they operate with devilish flair: When they happen upon virus-infected cells, they force them to self-destruct. Killers’ excellent memories also give them a predilection for grudges—enemies that trouble them twice should expect to be trounced with extra gusto. Thrill seekers might be drawn to killers, but Avery August, an immunologist at Cornell University, points out that these cells, also called cytotoxic T cells, might be all take and no give. Scientifically, they’re full of intrigue; romantically, he told me, “not so much”—at least for him.
Then there are the helpers—the benign Jekyll to the killers’ bellicose Hyde. Helper Ts are some of the most loyal partners you’ll find in the immune system, nurturing almost to a fault and versatile to boot. They coax B cells into maturing into antibody factories. They cheer killers along their murderous paths. They even goad innate immune cells into becoming the most ferocious fighters (and feeders) they can be. Effectively, helpers are “badass multitaskers that coordinate every level of immunity,” Marion Pepper, an immunologist at the University of Washington, told me. They’re about as supportive as they come—as long as you don’t mind being micromanaged from time to time.
It’s easy to see the appeal of antibodies. They’re among the few immune-system soldiers that can annihilate viruses before they enter cells, and they’re thought to be crucial to most vaccines. They can also be team players, throwing up red flags around microbes in order to alert other defenders to their presence. Transferred from animal to animal, or human to human, antibodies can confer protection against COVID-19; synthetic versions of the molecules are also relatively straightforward to manufacture en masse. Scoring a date with an antibody is a bit like finally getting together with the most popular person in school.
But counting on antibodies, and only antibodies, for protection is like shacking up with the first eligible suitor you meet—a risky and perhaps close-minded gamble. In the same way that our immune systems can guard against multiple pathogens at once, we could stand to be a bit less monogamous with our affections.
Besides, the choice might not ultimately be ours to make. Love is a two-way street, and antibodies are incorrigibly picky. Their sole mission is to glom on to a very specific microbe and cling to it, ignoring everything else along the way; it’s largely them doing the picking and choosing. And if you’re not the soul mate they imagined, there’s little you can do to change their minds—they’re proteins, and they don’t have one.
Really, it’s not them. It’s you.
