Every day you breathe in, swallow and touch enormous numbers of microbes, and almost none of them gain a foothold. The system that stops them has no single organ. It is spread through the bone marrow, the thymus, the lymph nodes, the spleen and the blood, and it works in layers. Vaccines have changed the health of whole populations; this level looks at what happens inside one body.

Barriers

The first line of defense is simply keeping microbes out. Unbroken skin is a tough, dry wall. Mucus traps invaders in the airways, stomach acid kills many that are swallowed, and tears and saliva contain an enzyme, lysozyme, that breaks down the walls of some bacteria.

Innate defense: fast and general

When microbes get past the barriers, through a splinter for instance, damaged cells release chemical alarms. Nearby blood vessels widen and leak, producing inflammation, whose four classic signs are redness, heat, swelling and pain. White blood cells called neutrophils rush in within hours, followed by larger cells called macrophages, a name meaning "big eaters." Both perform phagocytosis, in which a cell engulfs and digests an invader. The Russian zoologist Élie Metchnikoff discovered it in 1882 when he pushed thorns into transparent starfish larvae and watched mobile cells gather around the thorn to engulf it. This innate system responds within hours and treats every invader in much the same way, but it does not learn.

Adaptive defense: slow and specific

The second layer is built from white cells called lymphocytes. Each one carries a receptor that fits one particular molecular shape, called an antigen, usually a piece of a microbe. The body makes billions of lymphocytes with different receptors, shuffled almost at random, so for nearly any invader a few will fit. When one meets its match, it multiplies into an army of identical cells.

There are two main kinds. B cells make antibodies, Y-shaped proteins that latch onto a specific antigen, blocking viruses from entering cells and tagging microbes for destruction. T cells come in two broad types. Helper T cells coordinate the response, switching on B cells and other defenders. Killer T cells destroy the body's own cells that have been infected, stopping a virus from using them as factories.

Finding and multiplying the right cells takes time. A first encounter takes roughly one to two weeks to reach full strength, which is why a new infection can make you ill for days while the adaptive response builds.

Memory

When an infection is beaten, most of the army dies off, but long-lived memory cells remain. If the same microbe returns, they respond faster and harder, often clearing it before you notice any symptoms. That is why most people get chickenpox only once, although the chickenpox virus can hide in nerves and return decades later as shingles.

How vaccines work in the body

A vaccine shows the immune system an antigen so it can build memory without the disease. Older vaccines use killed microbes or living but weakened ones. Others use a single harmless protein from the microbe. Messenger RNA vaccines, widely used against COVID-19, deliver instructions wrapped in a tiny fatty bubble. Some cells near the injection site read the instructions and briefly make one viral protein, which the immune system then learns to recognize. The mRNA is broken down within days and never enters the cell's nucleus, so it cannot change a person's DNA. A sore arm or a mild fever afterward is a sign of innate defenses at work. Some vaccines need boosters, because memory can fade or because a virus changes, as influenza does from year to year.

When the system misfires

An allergy is an immune overreaction to a harmless substance such as pollen, peanuts or cat dander. Cells release histamine, causing itching, sneezing and swelling; a severe whole-body reaction, anaphylaxis, is treated at once with an adrenaline injection. In autoimmune disease the system attacks the body's own tissue: type 1 diabetes, rheumatoid arthritis and multiple sclerosis are examples. And some infections attack the immune system itself. HIV destroys helper T cells, and without treatment, as they fall, the whole adaptive system weakens, leading to AIDS. Modern antiretroviral drugs now allow people with HIV to live close to a normal lifespan.

Worked example: two children meet measles

A child with measles coughs in a classroom. Two of the children nearby have never had the disease. The first has had two doses of the measles vaccine. When the virus lands in her airway, memory B and T cells recognize it almost at once, antibodies rise within days and the virus is cleared, usually before she feels anything. Two doses protect about 97 percent of people. The second child is unvaccinated. For days the virus multiplies quietly while his innate defenses fight a holding action. Only after about a week or two does his adaptive response reach full strength, after fever, cough and a spreading rash. He will probably recover, but measles kills or disables some children, and research suggests it can also erase part of the immune memory the child had already built against other germs. Both children end up immune. Only one had to be sick to get there.