Your immune system has two departments. The first is the night watch: cells that patrol your body and attack anything that looks broadly foreign, a bacterium’s wall, a virus’s genetic material, a damaged cell. They are fast and useful, but they are generalists. They can tell that something is wrong; they can’t tell exactly what. The second department is the detective agency, and it is one of the most remarkable systems in biology. Its job is to recognise one particular invader precisely, deal with it, and then never forget it.
The detectives are two kinds of white blood cell, called B cells and T cells. Each one carries on its surface a receptor, a protein shaped to fit one particular shape and almost nothing else. That shape might be a small piece of a protein on the surface of a virus, or a fragment of a bacterium. Immunologists call these recognisable shapes antigens. One B cell might recognise a bump on a flu virus. The next might recognise a fragment of tetanus toxin. The next, something no germ has ever had.
Here’s the astonishing part. Your body doesn’t wait to see what germs turn up and then design receptors to match. It makes billions of different B and T cells in advance, each with a randomly assembled receptor, by shuffling and stitching together a few hundred gene segments in different combinations, in every developing cell. The result is a library of billions of shapes, so vast that for almost any germ you could ever meet, a few of your cells already happen to fit it. You were born with detectives for diseases that haven’t evolved yet.
The catch is that there are only a few of each. When a new germ arrives, the handful of B and T cells that fit it have to find it, be activated, and then multiply, again and again, into an army big enough to win. That takes time, usually one to two weeks. Meanwhile the germ is multiplying too. This is why the first time you meet a disease can be so dangerous: the detectives are brilliant, but they start every new case days behind.
As the army grows, it fights in several ways. Activated B cells become factories, pumping out thousands of antibodies a second: Y-shaped proteins with the same shape-matching tips as their parent cell’s receptor. Antibodies stick to the germ, blocking the parts it uses to enter your cells and flagging it for destruction. Some T cells, called killer T cells, find your own cells that have been infected and destroy them before the virus inside can finish copying itself. Other T cells, helpers, coordinate the whole response.
Then, when the infection is over, most of the army dies off. But not all of it. A population of memory B and T cells, which recognise that same germ, survives for years, sometimes for life. If the same germ ever returns, these cells are already waiting, in far greater numbers than before, and the response begins within days instead of weeks. Often the germ is cleared before you even feel ill. This is why you usually catch chickenpox only once.
A vaccine is a way of getting that memory without the dangerous first meeting. It shows your immune system the germ’s antigens, its wanted poster, in a form that can’t make you seriously ill: a killed or weakened version of the germ, a single harmless protein from its surface, or, in mRNA vaccines, a set of temporary instructions that lets your own cells briefly make that protein for the immune system to study. The matching B and T cells activate and multiply exactly as they would in a real infection, and leave behind memory cells. The slow, risky part of the first meeting has been done in advance, safely.
The idea is older than the science. In 1796, the English doctor Edward Jenner noticed that milkmaids who had caught cowpox, a mild disease, seemed protected from smallpox, a deadly one. He took material from a cowpox sore and scratched it into a boy’s arm, then later exposed him to smallpox. The boy didn’t fall ill. Nobody then knew about antigens or B cells; we now know that the two viruses share enough shapes that memory of one protects against the other. The word vaccine comes from vacca, Latin for cow.
What followed is one of humanity’s great achievements. Smallpox, which killed hundreds of millions of people in the twentieth century alone, was declared eradicated in 1980, after a worldwide vaccination campaign. Polio, which once paralysed hundreds of thousands of children a year, has been driven out of almost every country on Earth. India, which recorded its last case of wild polio in 2011, was certified polio-free in 2014, after one of the largest vaccination drives ever attempted, reaching more than a hundred and seventy million children in a single round.
Your immune system is a detective with a library of billions of faces and an extraordinary memory. All a vaccine does is show it the right photograph, before the crime.