Cell Recognition & Immune System

The immune system protects the body from harmful invaders (pathogens) and abnormal cells. It does this in two stages — a non-specific response (the same response to any pathogen, e.g. phagocytosis) and a specific response (involving lymphocytes, which target one particular pathogen).

Antigens

How does the body recognise a pathogen?

Every cell has specific molecules on its surface that act as identifiers — these are antigens. They can be proteins, glycoproteins, or glycolipids.

Antigens are how the immune system distinguishes self (own body cells) from non-self (foreign cells).

• Self antigens — on the body’s own cells; do not trigger an immune response
• Non-self antigens — on pathogens, transplanted cells, or abnormal body cells; do trigger an immune response

Antigens are used to detect:

• Pathogens — disease-causing organisms (bacteria, viruses, fungi)
• Cells from other organisms of the same species — important for organ transplant rejection
• Abnormal body cells — e.g. cancer cells, virus-infected cells
• Toxins — poisons (e.g. produced by some bacteria)

Antigen Variability

Some pathogens (e.g. influenza, HIV) have antigens that change frequently due to mutations in the genes that code for them. This is called antigen variability.

Effects on disease and prevention:

• Memory cells from a previous infection no longer recognise the new antigen. The immune system has to respond from scratch each time, so you can catch the same disease repeatedly (e.g. flu)
• Vaccines become ineffective — last year’s flu vaccine doesn’t protect against this year’s strain, as the antigens have changed.
• This is why we often need a new flu vaccine every year

Phagocytosis (Non-specific Response)

Phagocytosis is the first line of defence against pathogens. It is non-specific — the same response happens to any pathogen. It’s carried out by phagocytes (a type of white blood cell).

1. The phagocyte recognises non-self antigens on the pathogen and is attracted by chemicals released by the pathogen (chemotaxis)
2. The phagocyte engulfs the pathogen by surrounding it with its cell-surface membrane, forming a vesicle called a phagosome
3. A lysosome fuses with the phagosome
4. Lysozymes (the hydrolytic enzymes inside the lysosome) hydrolyse / digest the pathogen
5. The harmless products are absorbed by the phagocyte; some antigens are displayed on the phagocyte’s surface — it becomes an antigen-presenting cell (APC), which triggers the specific immune response

Specific Immune Response

After phagocytosis (non-specific response) the body launches a specific response targeted at the particular pathogen. This includes:

• Cellular response — by T lymphocytes (T cells)
• Humoral response — by B lymphocytes (B cells) and antibodies

Both are triggered by antigen-presenting cells (APCs) - this is where the pathogen’s antigens are displayed on the APC’s surface.

Cellular Response (T Lymphocytes)

T lymphocytes mature in the thymus and respond to antigens displayed on Antigen Presenting Cells (APCs).

Cellular Response Process

1. An antigen-presenting cell (e.g. a phagocyte, as we just looked at) displays the pathogen’s antigen on its surface. Note: This could be other antigen-presenting cells (e.g. cells infected by virus, cancer cells, foreign cells).
2. A helper T cell with a complementary receptor binds to the antigen (clonal selection)
3. This activates the helper T cell, which divides by mitosis (clonal expansion) — producing many identical helper T cells
4. The activated helper T cells then stimulate:
   • Cytotoxic T cells — these kill virus-infected cells and tumour cells (see below)
   • B cells — to start the humoral response (see below)
   • Phagocytes — to perform more phagocytosis
   • Memory T cells — ready for a rapid response to any future infection by the same pathogen
   • Note: For the AQA spec you don’t need to know the role of other T cells (e.g. regulatory T cells)

Cytotoxic T Cell

• These destroy abnormal (e.g. cancer cells) or infected cells
• They do this by releasing a protein called perforin
• This forms a pore in the cell-surface membrane, which allows cells and substances to freely enter and exit, and as a result the cell dies

Humoral Response (B Lymphocytes)

B lymphocytes mature in the bone marrow. Each B cell has a unique antibody on its surface (a B cell receptor) that’s complementary to one specific antigen.

Humoral Response Process

1. A B cell with the complementary receptor (this is the antibody on its surface) binds to the foreign antigen
   • This is clonal selection - the antigen “selects” the B cell with the matching antibody
2. The B cell takes in the antigen (internalises it), processes it, and presents it on its surface
   • This is now an antigen-presenting cell (APC)
3. A helper T cell binds to this same B cell (APC) and activates it
   • (Extra detail ~ T helper cells release cytokines which activate the B cell)
4. The activated B cell divides by mitosis
   • This is clonal expansion - producing many identical clones of the selected B cell
5. The clone of B cells differentiates into:
   • Plasma cells — secrete large numbers of monoclonal antibodies (all identical, specific to the original antigen)
   • Memory cells — stay in the blood long-term, ready for a rapid response to any future infection by the same pathogen

Antibodies

All the monoclonal antibodies produced by the plasma cells are identical and bind to the same specific antigen on the pathogen, so they can be used by the immune system to destroy that specific pathogen.

Antibody Structure

• Antibody is a quaternary protein - made of 4 polypeptide chains: 2 heavy and 2 light chains
• These chains are held together by disulfide bridges
• There are two identical variable regions, with the antigen-binding sites at the tips
• The variable region’s amino acid sequence is specific to one type of antigen — so one antibody can only bind to one type of antigen
• The rest of the molecule is the constant region (the same in all antibodies)

Why are antibodies important?

When an antibody binds to its specific antigen, they form an antigen-antibody complex. The pathogen is then destroyed in two ways:

• Agglutination — each antibody has two binding sites, so it can stick to two bacteria at the same time, acting as a bridge between them. Many antibodies doing this clump the bacteria together, making them too big to enter cells and easier for phagocytes to engulf
• Phagocytosis — the clumped pathogens are then engulfed and destroyed by phagocytes (as above)

Antibodies can also neutralise toxins released by bacteria — binding to the toxin prevents it from affecting cells.

Primary vs Secondary Immune Response

Your body reacts differently depending on whether it’s the first time a specific pathogen enters the body, or whether you have already encountered it before.

Primary Response (Slow, Fewer Antibodies)

• The first time the body meets a pathogen is called the primary response.
• It is generally slow, and creates only a few antibodies.
• Why? Because it has to go through the humoral response process, where the correct B cell needs to be selected (clonal selection) and then divide by mitosis (clonal expansion) to produce plasma cells, which can then produce antibodies. After this has happened, memory cells are produced.
• The person often shows symptoms of the disease.

Secondary Response (Faster, Lots of Antibodies)

• The next time the body meets the same pathogen is called the secondary response.
• It’s faster and creates lots of antibodies, often clearing the infection before symptoms appear.
• Because memory cells are already specific to the antigen and there are many of them, clonal selection is much faster — they recognise the antigen almost immediately, then divide rapidly into plasma cells.

Vaccination

A vaccine contains antigens from a pathogen in a form that can’t cause disease — usually a dead (inactivated) or weakened pathogen. The body responds as if it’s a real infection — producing a primary immune response, which produces memory cells.

If they later meet the real pathogen, they have a secondary immune response straight away, so don’t develop symptoms.

Herd Immunity

If a large enough proportion of the population is vaccinated, the pathogen can’t spread easily — even people who aren’t vaccinated are protected because they’re unlikely to come into contact with the pathogen.

This is important for:

• People who can’t be vaccinated (e.g. infants, the immunocompromised)
• Stopping outbreaks spreading through a population

Active vs Passive Immunity

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