Self & Other · The First Responders
The Assassins
When you get a cut, and after a day or two it produces a yellowish-white liquid that everyone calls “pus” — that liquid is mostly dead neutrophils. They went in. They did the job. They did not come back. The pus is, in a strange way, a memorial.
Neutrophils are not subtle. They damage tissue around them while they work. They occasionally attack things they shouldn’t. The body tolerates this because they are fast, fearless, and they buy time for the more careful cells to figure out what’s actually going on.
The Assassins
Most of the time, the immune system is dealing with things from the outside — bacteria, viruses, dust, the occasional splinter. But sometimes the trouble is inside, in cells that already belong to you.
A cell can go wrong in two important ways. It can get infected by a virus, which hijacks the cell’s machinery to make more viruses. Or it can mutate in a way that turns it into a cancer cell. In both cases, the body has a problem: the troubled cell looks, on the outside, almost identical to its healthy neighbors. It’s not waving a foreign flag. It’s a citizen who has been quietly turned.
For this, your body has assassins.
They’re called natural killer cells, or NK cells — a name so blunt that immunologists have been mildly embarrassed about it for fifty years, but no one has come up with a better one. NK cells patrol your tissues looking not for “things that are different from me” but for “things that should be wearing the right ID and aren’t.”
Every cell in your body wears, on its surface, a kind of molecular ID badge. (We’ll meet these badges properly in Chapter 6 — they’re called MHC molecules, and they’re so important they get their own chapter.) Healthy cells display their badges constantly. Some viruses, in an attempt to hide, force the cells they’ve infected to stop displaying badges. Some cancer cells stop displaying them too, for similar reasons.
NK cells respond to this absence with a kind of cold logic: a cell with no badge is suspicious, and a suspicious cell gets killed. They do this by injecting the target with chemicals that tell the target to die — not violently, not messily, but neatly, by activating a cellular self-destruct program called apoptosis. The infected or cancerous cell folds itself up quietly and is then cleaned up by the macrophages, who are always nearby, watching.
It is a strange thing to think about. Right now, in your body, there are cells whose job it is to walk around and quietly kill any of your other cells that look slightly off. They have probably done this several times today, to cells you would never have noticed, for reasons you will never know. The system mostly works.
The Chemistry Layer
Not all of your innate immunity is cells. Some of it is just chemistry.
Floating in your blood, all the time, is a set of about thirty proteins collectively called complement. They were named in the 1890s, when researchers discovered that they “complemented” the work of antibodies — they didn’t know what the proteins did, but they knew that antibodies didn’t work without them. The name stuck, even though we now know complement is far older than antibodies and does plenty on its own.
Complement is, among other things, a kind of immune Velcro. When a complement protein bumps into a bacterial surface, it sticks. Then a second protein binds to the first. Then a third. The cascade continues — protein after protein joining the stack — until either the bacterium is studded with so much molecular tag that any passing macrophage will instantly recognize it as food, or the proteins assemble themselves into a kind of microscopic drill that punches a hole straight through the bacterial wall and the bacterium dies of, essentially, leakage.
Complement is fast. It is tireless. It does not need to be told anything by anyone — it just floats around, binding to surfaces it doesn’t like, until something happens. It is one of the oldest defenses in evolution, older than any cell with a nucleus. Versions of it exist in horseshoe crabs, in coral, in jellyfish. It has been killing bacteria for somewhere between five hundred million and a billion years, depending on whom you ask.
You inherited it. You didn’t earn it. It works while you sleep.
The Messengers
We have one more cell to meet in this chapter, and it is, in some ways, the most important. It is also the one that connects this whole chapter to the next.
Dendritic cells were discovered in 1973 by a young researcher named Ralph Steinman, who thought he was looking at a weird kind of macrophage and turned out to be looking at something much more interesting. (He won the Nobel Prize for this in 2011, three days after he died of cancer. Nobel rules normally don’t allow posthumous awards, but his death was so recent that the committee made an exception.)
A dendritic cell looks like a starfish with too many legs — long, thin, spidery projections reaching out in all directions. It lives in tissue, like a macrophage, and it eats things, like a macrophage. But what it does next is different.
After a dendritic cell eats a bacterium or a virus, it does not simply digest the whole thing. It carefully takes pieces — small, specific protein fragments, a kind of molecular evidence file — and brings them up to its own surface. Then, holding those fragments out in front of it like Exhibit A, the dendritic cell stops what it’s doing, leaves the tissue, and travels through the lymphatic system to the nearest lymph node.