Antigens, Antibodies and the Immune Response

1Why this matters

You can catch a cold many times, yet a person who has had measles almost never catches it again. The difference is the third line of defence: the adaptive immune system. It recognises each pathogen individually, builds a weapon that fits that pathogen alone, and remembers it for years. It is slower than the innate system, taking days to respond the first time, but it is precise, and its memory is the reason vaccines work.

2Self and non-self: antigens

Every cell carries molecules on its surface, mostly proteins and carbohydrates, a little like a school uniform. Your immune system learns to leave your own molecules ("self") alone. An antigen is any molecule that the immune system recognises as foreign ("non-self") and that triggers an immune response. Examples include the proteins on the coat of a virus, molecules in a bacterial cell wall, and toxins released by bacteria. Each kind of pathogen has antigens with its own particular shape.

3Lymphocytes: B cells and T cells

Lymphocytes are white blood cells made in the red bone marrow. B cells mature in the bone marrow; T cells move to the thymus, a gland in the chest, to mature. Each lymphocyte carries receptors that fit just one antigen shape, and millions of different lymphocytes are made before you ever meet a pathogen. They wait in the lymph nodes and the spleen. The swollen "glands" in your neck during a sore throat are lymph nodes where lymphocytes are multiplying.

4Antibodies

An antibody (also called an immunoglobulin) is a Y-shaped protein made by activated B cells called plasma cells. The two tips of the Y are antigen-binding sites, whose shape is complementary to one particular antigen, like a key cut to fit one lock. An antibody against the measles virus therefore has no effect on the influenza virus. Antibodies work in several ways:

• Neutralisation: they cover the parts of a virus or toxin that would attack your cells. Antibodies that neutralise toxins are called antitoxins.
• Agglutination (clumping): each antibody has two binding sites, so it can link two pathogens. Many antibodies stick pathogens together in clumps that cannot spread and are easy for phagocytes to engulf.
• Marking for phagocytes: a pathogen coated in antibodies is engulfed much faster.
• Activating complement: antibody-coated bacteria attract complement proteins, which burst them.

5The immune response, step by step

1. A phagocyte (a macrophage, or a dendritic cell in the skin and airways) engulfs a pathogen and displays pieces of its antigens on its own surface. It is now an antigen-presenting cell.
2. A helper T cell whose receptors fit that antigen binds to it, is activated, and releases chemical signals.
3. The B cell whose receptors fit the same antigen is stimulated by the helper T cell. It divides again and again, making a clone of identical cells (clonal expansion). Most become plasma cells, which release huge numbers of antibodies into the blood and lymph. This antibody response is the humoral response.
4. Cytotoxic (killer) T cells are also activated. They find body cells infected by the virus and destroy them before the virus can multiply further. This is the cell-mediated response.
5. Some of the new B and T cells become memory cells, which remain in the body for years, even decades.

Helper T cells coordinate the whole response. HIV destroys exactly these cells, which is why it damages the entire immune system (unit 14).

Worked example: primary and secondary responses

A student's blood is tested for antibodies against one virus. The first exposure is on day 0. A second exposure to the same virus happens six months later, which is again called day 0 in the second row.

Step 1: compare the speed. After the first exposure, antibodies begin to appear only after about 5 days. This delay is the lag. After the second exposure, the level is already high by day 3.

Step 2: compare the size. The primary peak is 20 units. The secondary peak is 400 units, which is 400 ÷ 20 = 20 times higher.

Step 3: compare how long it lasts. By day 20 the primary level has fallen to 4 units, but the secondary level is still 150.

Step 4: explain. In the primary response, the few B cells that fit the antigen must first be found, activated and cloned, which takes days, and meanwhile the virus multiplies, so the person falls ill. The primary response leaves memory cells behind. In the secondary response, the many memory cells divide at once into plasma cells, so antibodies are made faster, in larger amounts and for longer. The virus is usually destroyed before it can cause symptoms: the person is now immune.

Practice