Revise The immune system for Cambridge 9700 (11.1)

The non-specific immune system provides an immediate, generalised response to any pathogen. It acts as the first barrier and a rapid-response team.

• Physical and Chemical Barriers: The skin is an impermeable barrier. Mucous membranes in the respiratory and digestive tracts trap pathogens, while cilia sweep them away. Chemical barriers include hydrochloric acid in the stomach and the enzyme lysozyme in tears and saliva, which breaks down bacterial cell walls.
• Phagocytosis: This is a key cellular defence where specialised white blood cells called phagocytes (e.g., neutrophils and macrophages) engulf and destroy pathogens. The process is as follows:
  1. Chemotaxis: Phagocytes are attracted to chemicals released by pathogens or inflamed tissues.
  2. Attachment: The phagocyte's receptors bind to the surface of the pathogen.
  3. Engulfment: The phagocyte's membrane extends to surround the pathogen, enclosing it in a vesicle called a phagosome.
  4. Fusion: Lysosomes, containing powerful hydrolytic enzymes, fuse with the phagosome to form a phagolysosome.
  5. Digestion: The enzymes digest and destroy the pathogen.
  6. Presentation: Macrophages can present the pathogen's antigens on their own cell surface, becoming Antigen-Presenting Cells (APCs). This is a crucial step in activating the specific immune system.

If pathogens breach the non-specific defences, the specific immune system is activated. It targets specific antigens (molecules on the pathogen's surface) and develops immunological memory. The key players are lymphocytes, which originate in the bone marrow.

• T-lymphocytes (T-cells): Mature in the thymus gland. They are responsible for cell-mediated immunity.
• B-lymphocytes (B-cells): Mature in the bone marrow. They are responsible for humoral immunity (involving antibodies in body fluids like blood and lymph).

The cell-mediated response is crucial for tackling pathogens that have infected the body's own cells (e.g., viruses) and for coordinating the overall immune attack.

1. Activation: A helper T-cell (Th) with a specific receptor binds to a complementary antigen presented by an APC (like a macrophage).
2. Clonal Expansion: This binding activates the helper T-cell, causing it to divide rapidly by mitosis (clonal expansion) and produce clones.
3. Cytokine Release: The activated helper T-cells release chemical messengers called cytokines (e.g., interleukins). These cytokines have several effects:
   • Stimulate B-cells to divide and differentiate (part of the humoral response).
   • Activate cytotoxic T-cells (Tc), also known as T-killer cells.
   • Enhance the activity of phagocytes.
4. Destruction of Infected Cells: Cytotoxic T-cells recognise and bind to infected body cells that display the specific pathogen antigen. They then release a protein called perforin, which creates pores in the infected cell's membrane, causing it to undergo lysis (burst) and die.
5. Memory: Some T-cells differentiate into memory T-cells, which remain in the body for long-term immunity.

The humoral response targets pathogens and toxins circulating freely in the body fluids.

1. Clonal Selection: A specific antigen on a pathogen binds to the complementary antibody-like receptor on the surface of a B-cell. This 'selects' the B-cell for activation. Often, this activation is confirmed by cytokines from an activated helper T-cell.
2. Clonal Expansion: The selected B-cell divides rapidly by mitosis, creating a large clone of identical cells.
3. Differentiation: These clones differentiate into two main cell types:
   • Plasma Cells: These are antibody factories. They are short-lived but produce and secrete vast quantities of specific antibodies into the blood and lymph.
   • Memory B-cells: These are long-lived cells that remain in circulation. They provide immunological memory, allowing for a much faster and stronger response if the same pathogen is encountered again.

Antibodies (immunoglobulins) are Y-shaped proteins made of four polypeptide chains: two identical heavy chains and two identical light chains, joined by disulfide bonds. Each antibody has:

• Variable Regions: At the tips of the 'Y', these form two identical antigen-binding sites. The unique amino acid sequence here makes them specific to one antigen.
• Constant Region: The 'stem' of the 'Y', which is the same for all antibodies of a given class. This region binds to receptors on immune cells (like phagocytes) or activates other immune processes.

Antibodies neutralise pathogens via several mechanisms:

• Agglutination: Each antibody has at least two binding sites, allowing them to clump pathogens together. This immobilises the pathogens and makes them easier for phagocytes to engulf.
• Opsonisation: Antibodies coat the surface of a pathogen, marking it as a target for phagocytes. The constant region of the antibody binds to receptors on the phagocyte, facilitating phagocytosis.
• Neutralisation: Antibodies bind to toxins produced by bacteria or to the surface of viruses, blocking them from binding to and damaging host cells.
• Complement Activation: The binding of antibodies to a pathogen can activate a cascade of proteins called the complement system, which can directly lyse the pathogen.

The immune system's response differs significantly between the first and subsequent encounters with a pathogen.

• Primary Response: Occurs on first exposure to an antigen. It is relatively slow, taking several days to build up, as it involves clonal selection, expansion, and differentiation. The concentration of antibodies produced is relatively low, and the response is short-lived.
• Secondary Response: Occurs on any subsequent exposure to the same antigen. Thanks to the presence of memory B and T cells, the response is much faster, stronger, and longer-lasting. Memory cells are rapidly activated, leading to a quicker and larger-scale production of plasma cells and antibodies. This often prevents the individual from experiencing any symptoms of the disease.

Immunity can be broadly categorised by how it is acquired and whether the body actively produces antibodies.

• Active Immunity: The body's immune system produces its own antibodies and memory cells in response to an antigen. This provides long-term protection.
  • Natural Active Immunity: Acquired after exposure to an actual pathogen (e.g., recovering from measles).
  • Artificial Active Immunity: Acquired through vaccination, where attenuated (weakened), dead, or parts of pathogens (antigens) are introduced to stimulate an immune response without causing disease.
• Passive Immunity: The body receives pre-formed antibodies from an external source. This provides immediate but short-term protection as no memory cells are formed.
  • Natural Passive Immunity: Acquired when antibodies are passed from mother to child (e.g., across the placenta or via breast milk).
  • Artificial Passive Immunity: Acquired through the injection of antibodies (e.g., antitoxins for tetanus or rabies antiserum).

Vaccination programmes are vital for public health. By introducing antigens, vaccines stimulate a primary immune response, leading to the formation of memory cells. This means that if the vaccinated individual encounters the actual pathogen, a rapid and strong secondary immune response can be mounted, preventing illness. Widespread vaccination also contributes to herd immunity, where a large proportion of the population is immune, making it difficult for the pathogen to spread and protecting those who cannot be vaccinated (e.g., infants, immunocompromised individuals).