The immune system

Syllabus points

• Describe the mode of action of phagocytes.
• Explain the meaning of the terms antigen, self and non-self.
• Describe the roles of B lymphocytes and T lymphocytes.
• Explain the role of memory cells in long-term immunity.

Antigens, self and non-self

An antigen is a molecule, usually a protein or glycoprotein, that the immune system recognises as foreign and that stimulates an immune response.

Antigens sit on the outside of cells. From topic 4.1, the glycoproteins and glycolipids of the cell surface membrane are exactly these molecules, and they differ between individuals and between species.

• Self antigens are the body's own. The immune system learns during development not to attack them.
• Non-self antigens belong to pathogens, to transplanted tissue, or to cells that have changed, such as cancer cells.

When that discrimination fails and the body attacks its own tissue, the result is an autoimmune disease.

Antigen recognition works exactly like enzyme specificity: a receptor with a complementary shape binds one antigen and not others.

Phagocytes: the non-specific response

Phagocytes act against anything foreign, without needing to recognise which pathogen it is. They are made in the bone marrow and travel in the blood, squeezing out through capillary walls into infected tissue.

• Neutrophils are the most numerous, short-lived, and arrive first. They have a lobed nucleus.
• Macrophages are larger, longer-lived, and develop from monocytes that leave the blood and settle in tissue.

Phagocytosis

1. The phagocyte is attracted to the site by chemicals released by pathogens and damaged cells. This is chemotaxis.
2. It attaches to the pathogen, often helped by antibodies already stuck to it.
3. The cell surface membrane engulfs the pathogen, enclosing it in a vesicle called a phagosome.
4. Lysosomes fuse with the phagosome and release hydrolytic enzymes into it.
5. The enzymes digest the pathogen, and the useful products are absorbed into the cytoplasm.

Neutrophils die in the process, and dead neutrophils are the main constituent of pus.

Macrophages do something extra and important: after digesting a pathogen they display its antigens on their own cell surface membrane, becoming an antigen-presenting cell. This is the bridge between the non-specific and specific responses, because it is what allows a lymphocyte to encounter the antigen.

Lymphocytes: the specific response

Lymphocytes have a large round nucleus and very little cytoplasm. Both types are made in the bone marrow, and the difference is where they mature:

• B lymphocytes mature in the bone marrow.
• T lymphocytes mature in the thymus.

Each lymphocyte carries receptors of one shape only, determined before it ever meets an antigen. The body makes an enormous variety of them, so that for almost any antigen there is some lymphocyte somewhere that happens to fit.

Clonal selection and expansion

This is the central idea, and it explains why the specific response is slow at first.

1. An antigen enters the body.
2. Out of millions of lymphocytes, the few whose receptors are complementary to that antigen bind it. This is clonal selection: the antigen selects the cell, rather than the cell being made to order.
3. Those selected lymphocytes are activated and divide repeatedly by mitosis, producing a clone of identical cells all specific to that antigen. This is clonal expansion.
4. The clone differentiates into cells that do the work.

The delay of several days before antibody appears is the time taken for this division to happen, starting from a very small number of cells.

B lymphocytes

Activated B cells differentiate into two kinds:

• Plasma cells, which are antibody factories. They have extensive rough endoplasmic reticulum and many ribosomes, and secrete thousands of antibody molecules per second. They live only a few days.
• B memory cells, which remain in the body for years, ready to respond quickly if the same antigen returns.

This is the humoral response, so called because antibodies circulate in the body fluids.

T lymphocytes

Activated T cells differentiate into several kinds:

• T helper cells release chemicals called cytokines that stimulate B cells to divide, stimulate phagocytes, and activate T killer cells. Almost nothing in the specific response works properly without them, which is why HIV, which destroys them, is so devastating.
• T killer cells attack and destroy the body's own cells that are infected with a virus or have become cancerous. They attach to the target and release substances that make holes in its membrane, so it bursts.
• T memory cells, which persist and respond rapidly on re-exposure.

This is the cell-mediated response, and it deals with pathogens that have got inside cells where antibodies cannot reach them.

Primary and secondary responses

The whole point of memory cells shows up when the same antigen is met twice.

The primary response, on first exposure:

• there is a lag of several days while clonal selection and expansion happen
• the antibody concentration produced is low
• it takes a long time to rise, and falls away fairly quickly
• the person usually shows symptoms, because the pathogen has time to multiply

The secondary response, on a later exposure to the same antigen:

• memory cells are already present in large numbers and are already specific
• they divide and differentiate into plasma cells immediately, with almost no lag
• antibody concentration rises faster, reaches a much higher level, and stays raised for longer
• the pathogen is destroyed before it can multiply enough to cause symptoms, so the person is immune

Being able to describe both curves from a graph, and to explain the difference in terms of memory cells, is worth a great many marks across past papers.

Common mistakes

• Saying the immune system "makes an antibody to fit" a new pathogen. The lymphocyte with the right receptor already exists and is selected.
• Saying phagocytes are specific. They are non-specific; lymphocytes are specific.
• Mixing up where the two lymphocytes mature. B in bone marrow, T in thymus.
• Saying plasma cells are memory cells. Plasma cells secrete antibody and die within days; memory cells persist.
• Explaining the secondary response as "the body remembers", without naming memory cells and their rapid division into plasma cells.