Cambridge International AS & A Level Biology: Chapter 11 Immunity Study Notes

Fundamental Concepts of Immunity

• Definition of Immunity: Protection against disease provided by the body's internal defense or immune system. It allows humans to defend themselves against pathogens (disease-causing organisms).

• The Immune System: The body's internal defense system, consisting of physical, chemical, and cellular defenses.

  • External Defense System:

    • Epithelia: Effective barriers covering airways to prevent pathogen entry.

    • Hydrochloric Acid ($HCl$): Located in the stomach to kill bacteria ingested with food and drink.

    • Blood Clotting: Stops blood loss and prevents pathogen entry through skin wounds.

  • Internal Defense System: Involves white blood cells that recognize markers on pathogens.

• Antigen: A substance that is foreign to the body and stimulates an immune response (e.g., large molecules like proteins, glycoproteins, glycolipids, or polysaccharides). Pathogens produce toxins and waste materials that also act as antigens.

• Self: Substances produced by the body that the immune system does not recognize as foreign, thereby not stimulating an immune response.

• Non-self: Any substance or cell recognized by the immune system as foreign, which will stimulate an immune response.

• Immune Response: The complex series of responses to the entry of a foreign antigen, involving the activity of lymphocytes and phagocytes.

• Cell Surface Antigens: Molecules on the surfaces of individuals' cells. For example, in the $ABO$ blood group system, Type A blood has specific carbohydrate chains on glycolipids/glycoproteins. Giving Type A blood to a Type B recipient causes the recipient's immune system to recognize the A-antigens as non-self and produce antibodies.

Cells of the Immune System

• Origins: All immune cells are produced from stem cells in the bone marrow.

• Phagocytes: Scavengers that remove dead cells and invasive microorganisms.

  • Neutrophils:

    • Make up about $60\%$ of white blood cells.

    • Produced and stored in bone marrow.

    • Short-lived cells that travel in blood and squeeze through capillary walls into tissues.

    • Released in large numbers during infection.

  • Macrophages:

    • Larger than neutrophils.

    • Travel in blood as monocytes before settling in organs (lungs, liver, spleen, kidney, lymph nodes).

    • Long-lived cells that do not destroy pathogens completely; they cut them up to display antigens for lymphocytes.

The Mechanism of Phagocytosis

• Chemotaxis: Movement toward a chemical stimulus. Cells under attack release chemicals like histamine, which, along with pathogen chemicals, attract neutrophils.

• Recognition and Attachment: Neutrophils have surface receptor proteins that recognize antibody molecules coated on pathogens.

• Endocytosis: The neutrophil's cell surface membrane engulfs the pathogen, trapping it within a phagocytic vacuole.

• Lysosome Fusion: Lysosomes fuse with the vacuole, releasing hydrolytic enzymes (such as proteases) to break down the pathogen.

• Steps of Phagocytosis:

  1. Attraction (chemotaxis).

  2. Recognition and attachment (directly to membrane or via antibody 'marker').

  3. Endocytosis.

  4. Formation of a phagocytic vacuole containing bacteria.

  5. Fusion of lysosomes and phagocytic vacuole.

  6. Killing and digestion; digested products are released by exocytosis.

• Pus: Collection of dead neutrophils at an infection site.

Lymphocytes: B and T Cells

• Characteristics: Smaller than phagocytes with a large nucleus filling most of the cell.

• B-lymphocytes (B cells):

  • Mature in the bone marrow.

  • Each mature B cell is specialized to make just one type of antibody molecule.

  • Genes coding for antibodies are changed during maturation to create millions of different B cell types.

  • Clones: Small groups of identical cells produced by mitosis.

• T-lymphocytes (T cells):

  • Leave bone marrow and collect in the thymus (a gland in the chest) to mature.

  • The thymus doubles in size between birth and puberty, then shrinks.

  • Only mature T cells can carry out immune responses.

• Immune Response Logic: Mature lymphocytes circulate between blood and lymph to ensure distribution. Coordination between B and T cells is essential for effective defense.

Humoral Response: B-lymphocytes in Action

• Clonal Selection: When an antigen enters for the first time, only B cells with complementary cell surface receptors are stimulated to divide.

• Clonal Expansion: The selected B cells divide repeatedly by mitosis to produce huge numbers of identical cells over a few weeks.

• Plasma Cells: Short-lived activated B cells that secrete antibodies into blood, lymph, or gut/lung linings at a rate of several thousand per second.

• Memory B Cells: Long-lived activated B cells that circulate for a long time (basis of immunological memory). They divide rapidly if the same antigen is reintroduced.

• Primary Immune Response: The first response to a specific antigen; slow because few specific B cells exist.

• Secondary Immune Response: Subsequent response; faster and produces more antibodies because of the presence of memory cells.

Molecular Structure and Function of Antibodies

• Structural Composition: Globular glycoproteins (immunoglobulins) with quaternary structure.

  • Chains: Two identical 'heavy' (long) chains and two identical 'light' (short) chains.

  • Bonds: Disulfide bonds hold the polypeptide chains together.

  • Variable Region: Formed from parts of light and heavy chains; sequences of amino acids create a specific 3D shape complementary to an antigen.

  • Hinge Region: Provides flexibility for the molecule to bind to antigens.

• Types of Immunoglobulins:

  • $IgG$: Standard four-polypeptide Y-shaped molecule.

  • $IgA$: Four antigen-binding sites.

  • $IgM$: Ten antigen-binding sites.

• Functions of Antibodies:

  1. Combine with viruses to prevent cell entry/damage.

  2. Attach to bacterial flagella to reduce activity and ease phagocytosis.

  3. Agglutination: Clumping bacteria together to reduce spread.

  4. Lysis: Together with other molecules, they 'punch' holes in bacterial cell walls, causing them to burst via osmosis.

  5. Opsonization: Coating bacteria to make them easier targets for phagocytes (which have receptors for the antibody constant region).

  6. Antitoxins: Neutralize toxins (e.g., from cholera, diphtheria, or tetanus).

Cell-Mediated Response: T-lymphocytes

• T-cell Receptors: Specific cell surface receptors similar to antibodies.

• Antigen Presentation: T cells are activated when they recognize an antigen displayed on a host cell (like a macrophage or an infected body cell).

• T-helper Cells: Secrete cytokines (signalling molecules) to:

  • Stimulate B cells to divide and become plasma cells.

  • Stimulate macrophages to perform phagocytosis more vigorously.

  • Stimulate T-killer cells to divide.

• T-killer Cells (T-cytotoxic cells): Search for infected cells displaying foreign antigens. They attach to these cells and secrete toxic substances (e.g., hydrogen peroxide) to kill the cell and the pathogens within.

• Memory T Cells: Memory T-helper and memory T-killer cells are produced for rapid secondary responses.

Active and Passive Immunity

• Active Immunity: Immunity gained when an antigen enters the body, leading to an immune response and antibody production by the host.

  • Natural Active: Gained through infection by a pathogen.

  • Artificial Active: Gained through vaccination (injection or oral preparation of antigens).

• Passive Immunity: Temporary immunity gained without an immune response; no B or T cells are activated.

  • Natural Passive: Maternal antibodies crossing the placenta or through breast milk (colostrum, which contains $IgA$).

  • Artificial Passive: Injection of antibodies/antitoxins (e.g., tetanus antitoxin collected from blood donors for immediate protection).

Vaccines and Vaccination Programmes

• Vaccine Composition: May contain whole live organisms, dead organisms, attenuated (harmless) organisms, toxoids (harmless toxins), or surface antigens.

• Function: Mimics natural infection to stimulate an immune response and provide long-term immunity. Some require booster injections to maintain protection.

• Herd Immunity: Vaccinating a large proportion of a population (e.g., $93-95\%$ for measles) to reduce pathogen transmission, protecting those who cannot be vaccinated.

• Ring Immunity: Vaccinating people in the immediate area of an outbreak (the strategy used for smallpox eradication).

• Eradication Successes and Failures:

  • Smallpox: Declared eradicated by the WHO in $1980$.

  • Polio: Endemic in only three countries in $2018$ (Nigeria, Pakistan, Afghanistan) with only $29$ reported cases globally.

  • Measles: Difficult to eradicate due to high infectivity ($93-95\%$ coverage required), the need for boosters, and shifting populations/migrants.

Monoclonal Antibodies (Mabs)

• Monoclonal Antibody (Mab): An antibody made by a single clone of hybridoma cells; all molecules are identical and specific to one antigen.

• Hybridoma Method:

  1. Inject a mouse with a specific antigen.

  2. Mouse B cells divide into plasma cells in the spleen.

  3. Plasma cells (which produce antibodies but don't divide) are fused with cancer cells (which divide indefinitely but don't produce antibodies).

  4. Resulting hybridoma cells divide by mitosis and secrete identical monoclonal antibodies.

• Diagnostic Uses:

  • Locating blood clots: Labelled Mabs (e.g., with a radioactive chemical) bind to fibrin; detected by a gamma-ray camera.

  • Blood typing and tissue typing.

  • Detecting cancer cells by identifying specific surface proteins.

• Therapeutic Uses and Humanization: Foreign Mabs (mouse-derived) can trigger immune responses in humans. They are "humanized" by altering genes for human amino acid sequences and sugar group positions.

  • Trastuzumab (Herceptin™): Treats breast cancer by binding to receptors on cancer cells, marking them for destruction.

  • Ipilimumab: Treats melanoma by blocking proteins that suppress the immune response.

  • Infliximab: Treats rheumatoid arthritis by blocking a protein that damages joint cartilage.

  • Rituximab: Controls B-lymphocyte overproduction by binding to B cell surface receptors (used for leukaemias).

Questions & Discussion

• Antibodies vs. Antibiotics: Antibodies are glycoproteins produced by the body; antibiotics are chemicals (often from fungi) used to kill or inhibit bacteria.

• Mass Vaccination Advantages: Long-term benefits include eradication of diseases (saving lives and healthcare costs) and protection of vulnerable individuals through herd immunity.

• Blood Typing Logic: Red blood cells are recognized as self if they possess the individual's own antigens (A or B). If blood of Type B is given to someone with Type A, the Anti-B antibodies (if present) or the immune response will cause agglutination because Type B antigens are non-self.

• Discussion on Vaccination Resistance: Some people resist vaccination due to fear of harm, or attacks on healthcare workers (e.g., in Pakistan and Afghanistan), which hampers eradication efforts.