The Immune System: How Your Body Fights Germs and Remembers Them

A Body Under Constant Watch

Every breath you take, every bite of food and every object you touch carries microbes. Most of them are harmless, and many are even helpful, but some are pathogens: viruses, bacteria, fungi and parasites that can cause disease. The reason we are not ill all the time is the immune system, a network of organs, cells and molecules that protects the body from disease.

The immune system has a remarkably varied job. It must detect invaders as different as a tiny virus and a parasitic worm many times larger than a human cell. It also deals with the body's own cells when they turn into cancer cells, and with foreign objects such as a wooden splinter. Above all, it has to tell all of these apart from the body's own healthy tissue, so that it attacks what is dangerous and leaves the rest alone.

In humans and many other animals the immune system has two major parts. The innate immune system reacts quickly with a ready-made response to broad groups of threats. The adaptive immune system is slower to start but produces a response tailored to each specific invader, and it remembers invaders it has met before. Both rely on specialised cells and molecules, and they constantly work together.

The First Line of Defence: Barriers

The simplest way to stop an infection is to keep germs out in the first place. The body is surrounded by physical, chemical and biological barriers that do exactly that.

• Skin is a tough, waterproof wall. Its outer layer is made of dead cells that are constantly shed, taking microbes with them, and its surface is slightly acidic, which many bacteria dislike.
• Mucous membranes line the nose, mouth, airways and gut. Sticky mucus traps particles, and in the airways tiny hair-like structures called cilia sweep it upwards so it can be swallowed or coughed out.
• Chemical defences include the strong acid in the stomach, which kills many swallowed microbes, and enzymes such as lysozyme in tears and saliva, which can break down the walls of some bacteria.
• Friendly microbes living on the skin and in the gut take up space and nutrients, making it harder for harmful species to settle in.

Reflexes such as coughing and sneezing, and even the flushing action of urine, also help remove unwanted visitors. When a pathogen gets past these barriers, for example through a cut, the next line of defence takes over.

Innate Immunity: Fast and Ready

The innate immune system is the body's rapid response team. It is present from birth, acts within minutes to hours, and responds in much the same way each time it meets a particular kind of threat.

Recognising danger

Innate immune cells carry receptors that recognise molecular patterns shared by large groups of microbes but absent from our own cells, such as parts of bacterial cell walls or certain forms of viral genetic material. The best known of these sensors are the Toll-like receptors. Cells can also detect signals released by damaged or dying body cells, which warns them that something has gone wrong even before a germ is identified.

Cells that eat invaders

Some white blood cells are phagocytes, from Greek words meaning "eating cells". They engulf microbes and debris and destroy them inside the cell. Neutrophils, the most common type of white blood cell in human blood, rush to infected sites in large numbers. Macrophages are larger and longer-lived; they clean up dead cells and send chemical signals that call in other defenders. Dendritic cells also swallow invaders, but their most important task is to carry pieces of them to the lymph nodes and show them to the adaptive immune system.

Another innate cell, the natural killer (NK) cell, does not eat germs. Instead, it checks the body's own cells and destroys those that look abnormal, such as cells infected by viruses or some tumour cells.

Inflammation and fever

When tissue is injured or infected, immune cells release chemical messengers that cause inflammation. Blood vessels widen and become leakier, so more blood, fluid and defensive cells reach the area. This produces the classic signs known since ancient times: redness, heat, swelling and pain. Uncomfortable as it is, inflammation is a sign that the defence is working.

Some of these messengers also act on the brain and raise the body's temperature, causing fever. A higher temperature can slow the growth of some pathogens and helps certain immune reactions run faster.

The complement system

The blood also contains a group of proteins called the complement system. When activated, they set off a chain reaction that coats microbes so phagocytes can grab them more easily, attracts immune cells, and can even punch holes in the membranes of some bacteria.

Adaptive Immunity: The Body Learns

The adaptive immune system is what makes immunity truly personal. Its key players are white blood cells called lymphocytes, which come in two main types: B cells and T cells. Both are made in the bone marrow. B cells mature there, while T cells travel to the thymus, a small organ in the chest, to finish developing; this is where the "T" comes from.

Each lymphocyte carries receptors that recognise one particular molecular shape, called an antigen. Because the genes for these receptors are cut and reshuffled as each cell develops, the body ends up with an enormous variety of lymphocytes, each with a different receptor. Together they can recognise a vast range of shapes, including ones the body has never encountered. When a lymphocyte meets its matching antigen, it multiplies rapidly into an army of identical cells, all aimed at the same target. This process is called clonal selection.

Lymphocytes circulate through the blood and the lymphatic system, a network of vessels and hundreds of small bean-shaped lymph nodes. The spleen and the lymph nodes act as meeting points where lymphocytes can encounter antigens brought in by dendritic cells. This is why lymph nodes in the neck can become swollen and tender during a sore throat: immune cells there are multiplying.

B cells and antibodies

When activated, B cells turn into plasma cells that release large amounts of antibodies, Y-shaped proteins that float in blood and other body fluids. The tips of the Y fit a particular antigen like a key in a lock. Antibodies can block a virus from entering cells, clump bacteria together, neutralise toxins and mark invaders for destruction by phagocytes and the complement system. Mammals have five main classes of antibodies, called IgG, IgA, IgM, IgD and IgE, each suited to different jobs and places in the body.

T cells

T cells cannot recognise free-floating antigens. Instead, they inspect fragments of proteins displayed on the surface of other cells by special molecules called the major histocompatibility complex (MHC). Helper T cells act like coordinators: they release signals that activate B cells, macrophages and other T cells. Cytotoxic T cells are the killers: they find body cells infected by viruses, or some cancer cells, and order them to self-destruct. Other T cells help calm the immune response once a threat is over.

Immunological memory

After an infection is cleared, most of the expanded lymphocytes die off, but some remain as long-lived memory cells. If the same pathogen returns, these cells respond much faster and more strongly than the first time, often destroying it before any symptoms appear. This is why people usually catch diseases such as chickenpox only once. The first encounter with a germ typically takes days to produce a full adaptive response; a second encounter can be dealt with far more quickly.

Vaccines: Training Without the Illness

Vaccination uses immunological memory on purpose. A vaccine exposes the immune system to a harmless version or part of a pathogen, such as a weakened or killed germ, a single protein, or genetic instructions for making one. The body builds memory cells without having to suffer the disease.

The story is often traced to the English doctor Edward Jenner. In 1796 he showed that material from cowpox, a mild disease, could protect a person against smallpox, one of the deadliest diseases in history. The word "vaccine" comes from the Latin word for cow, vacca. Almost two centuries later, a worldwide vaccination campaign led the World Health Organization to declare smallpox eradicated in 1980, the first human disease to be wiped out.

Vaccines also protect people who cannot be vaccinated, such as very young babies or people with weakened immune systems. When enough people in a community are immune, a pathogen struggles to spread, an effect called herd immunity.

When the Immune System Gets It Wrong

A defence this powerful must be carefully controlled. While lymphocytes develop, those that react strongly against the body's own molecules are mostly removed or switched off, a process known as self-tolerance. Problems arise when the system reacts too much, against the wrong target, or too little.

• Allergies happen when the immune system overreacts to harmless substances such as pollen, dust mites or certain foods. IgE antibodies trigger cells to release histamine and other chemicals that cause sneezing, itching, swelling or, in rare severe cases, a dangerous reaction called anaphylaxis.
• Autoimmune diseases occur when the immune system attacks the body's own tissues. In type 1 diabetes, for example, it destroys the insulin-producing cells of the pancreas; in rheumatoid arthritis, it attacks the joints.
• Immunodeficiencies occur when part of the immune system is missing or weakened. Some people are born with them; others acquire them. HIV, for instance, infects and destroys helper T cells, and without treatment this leads to AIDS, in which the body can no longer fight off infections well.

Doctors must also manage the immune system after organ transplants. Because the new organ carries foreign MHC molecules, the recipient's T cells may attack it, so patients take medicines that dampen the immune response.

Surprising Facts About Immunity

• A starfish and a thorn. The zoologist Élie Metchnikoff discovered phagocytosis in the 1880s by pushing small thorns into transparent starfish larvae and watching mobile cells gather around them. He shared the 1908 Nobel Prize in Physiology or Medicine with Paul Ehrlich, who studied antibodies.
• Immunity starts before birth. Some antibodies (IgG) cross the placenta from mother to baby, and breast milk supplies IgA antibodies that protect the baby's gut. This borrowed protection lasts only for the first months of life.
• The thymus shrinks with age. It is most active in childhood and gradually gets smaller and is replaced by fat after puberty, yet adults keep a large supply of T cells made earlier in life.
• Even bacteria have immune systems. Many bacteria store snippets of viral DNA and use them to recognise and cut up those viruses if they attack again. Scientists turned this system, called CRISPR, into a famous gene-editing tool.
• Not all vertebrates use antibodies. Jawless fish such as lampreys have an adaptive immune system that relies on a completely different type of receptor, showing that nature invented adaptive immunity more than once.
• Fighting cancer with immunity. Modern immunotherapy medicines release the "brakes" on T cells so they can attack tumours. James Allison and Tasuku Honjo received the 2018 Nobel Prize in Physiology or Medicine for discoveries that made these treatments possible.

Keeping the Defences Strong

The immune system works best when the rest of the body is healthy. Getting enough sleep, eating a balanced diet with enough vitamins and minerals, staying physically active and keeping up with recommended vaccinations all support it. Simple habits such as washing hands also reduce the number of germs the immune system has to face in the first place.

From the acid in the stomach to memory cells that can last for decades, the immune system is a layered, constantly learning defence. It recognises an almost unlimited variety of threats, remembers past battles, and still manages, most of the time, to leave the body's own cells in peace.