Under the skin

A wall made of the dead

The outer layer is 15 to 20 sheets of flattened, dead cells called corneocytes: bags of keratin, stacked like bricks and sealed with fats. The whole wall is replaced from below roughly every month.

The surface is mildly acidic, around pH 5, and laced with antimicrobial peptides. Most microbes living here, like the pale Staphylococcus epidermidis, are tolerated residents that crowd out worse ones.

The thorn splits the wall. Riding it in are clusters of Staphylococcus aureus. Aureus means golden, for the pigment they make.

The first alarm

Beneath the wall lies the dermis: a scaffold of collagen cables threaded with capillaries and nerves. Sentinel cells wait here, already in position.

A mast cell is packed with hundreds of granules of histamine and other signals. Injury and bacterial molecules make it empty them within seconds.

Histamine loosens the walls of nearby vessels. Blood rushes in and fluid leaks out. The redness, heat and swelling of a wound are this, happening. Resident macrophages add chemical calls for help.

Leaving the bloodstream

Inside a venule, a small vein just past the capillaries, red cells tumble by, slowed here many times over. Carried with them are neutrophils, the most common white cells: roughly half to two thirds of them.

Where the wall is inflamed, sticky molecules called selectins snag a passing neutrophil. It rolls, brakes, and grips the wall with integrins.

Then it squeezes through a gap between two wall cells, narrower than itself. Its nucleus, split into lobes, can pass through in pieces. In the first hours after an injury, neutrophils are most of what arrives.

The chase

Bacteria shed formyl peptides, a chemical signature of their kind. The neutrophil turns toward the stronger trace and crawls, leading with a ruffled sheet of membrane.

An echo from deep time: your mitochondria were once free-living bacteria and still mark their proteins the same way. When your own cells are crushed, their mitochondria set off the same alarm.

The prey is engulfed and doused with hypochlorous acid, the active ingredient of household bleach, made by an enzyme called myeloperoxidase.

Some neutrophils go further. They burst, casting out their own DNA as a sticky net that snares microbes. Here it glows green, the way biologists stain it.

The big eater

Macrophage is Greek for big eater. Many arrive as monocytes from the blood and mature on site; others have lived in the tissue for years.

It reaches out with a cup of membrane, wraps its target and pulls it inside a bubble called a phagosome. The bubble fuses with lysosomes, sacs of digestive enzymes kept at about pH 4.5, shown here in orange.

It also clears away spent neutrophils and releases cytokines such as IL‑1 and TNF. Reaching the brain, these reset its thermostat. This is how a fever starts.

Four hundred times smaller

We drop onto the surface of a single rod-shaped bacterium that came in with the thorn. This scale is too fine for an ordinary light microscope; it has been mapped with electron microscopes and X‑ray crystallography.

Your blood carries more than 30 complement proteins, inert until they touch a microbe. Then they switch each other on in a cascade. Fragments called C3b stick to the surface: tags that mark it for eating.

The last proteins assemble into a ring, the membrane attack complex, and punch a pore about 10 nanometres wide through the outer membrane. Thin-walled bacteria like this one can burst. Staph's thick wall resists the punch, so against it the tags matter more.

The courier

The scale jumps: we pull back to follow a messenger. Dendritic cells in the skin have been sampling the invader. Carrying its fragments, one crawls into a lymphatic vessel and drifts toward the nearest lymph node, a trip of a day or so.

You have hundreds of lymph nodes, around 600, most smaller than a bean. Inside, B cells gather in round follicles and T cells fill the zone around them. Every node is a place where the right cells can find each other.

One in a million

The dendritic cell holds up fragments of the invader on molecules called MHC. T cells crawl over it by the thousands per hour, each touching briefly, testing the fit.

Each T cell carries one receptor design, built by randomly shuffling gene segments. Together yours carry an estimated 100 million or more designs. For any one invader, perhaps one naive T cell in a hundred thousand to a million fits.

When one does, the two cells lock into an immunological synapse, a bullseye of receptors. The T cell switches on.

An army from one

The activated T cell divides, and its daughters divide, as often as every six to eight hours. Ten doublings make 1,024 cells in about three days.

Within a week a single clone can number in the tens of thousands or more. Helper T cells coordinate the response. Killer T cells go hunting.

A quiet execution

Some enemies hide inside your cells, beyond the reach of antibodies: viruses, and bacteria that slip indoors. So nearly every cell in your body keeps displaying fragments of its own proteins on MHC class I molecules.

A killer T cell reads them. Finding a foreign fragment, it docks, aims its granules at the contact point and releases them. Perforin opens holes; granzymes pass through and trigger the cell's own self-destruct program.

The infected cell dies neatly, blebbing and breaking into sealed fragments that are swept up without spilling. The killer moves on to the next.

The factory

Back in the lymph node's follicles, B cells that recognise the invader get help from T cells and improve. Their antibody genes mutate and the tightest binders are selected: evolution, run over days and weeks, inside you.

Some become plasma cells, filled with rough endoplasmic reticulum. Each one releases thousands of antibody molecules every second.

Antibodies spread through blood and tissue and coat the invader. At this scale, each one is far too small to see.

The shape of a Y

An antibody is about 15 nanometres across: four protein chains folded into twelve compact domains.

Only the two tips differ from one antibody to the next. They fit one exact shape on the invader and grab it with both arms.

The stem is a handle. Macrophages and neutrophils carry receptors for it, so a coated bacterium is a marked one: easier to seize, faster to eat. The stem also sets off complement.

What stays

Within a couple of weeks the wound has closed. Most of the expanded army, around 90 to 95 percent, dies off on schedule.

The survivors become memory cells that can last for decades. Some settle in this patch of skin as resident guards. If the same invader returns, the response starts within hours, not days.