Cell Recognition and the Immune System

• Every cell in the body has glycoproteins on its surface that act as markers
• These are part of the Major Histocompatibility Complex (MHC) — unique to each individual
• Antigens are molecules (usually proteins or glycoproteins) on the surface of cells that trigger an immune response
• Self-antigens: Found on all the organism's own cells — the immune system recognises these as "self" and does not attack
• Non-self antigens: Found on pathogens, foreign cells, or abnormal cells — the immune system recognises these as foreign and mounts an attack
• Autoimmune disease: The immune system mistakenly attacks self-antigens (e.g., Type 1 diabetes, rheumatoid arthritis)

The first line of defence is non-specific — it responds the same way to all pathogens:

• Physical barriers: Skin, mucous membranes
• Chemical barriers: Lysozyme (in tears/saliva), stomach acid (HCl), antimicrobial peptides
• Phagocytosis: Phagocytes (neutrophils, macrophages) engulf and destroy pathogens
• Inflammation: Damaged cells release histamine → blood vessels dilate → increased blood flow → more white blood cells arrive

Phagocytosis (Detailed)

1. Phagocyte is attracted to the pathogen by chemotaxis (chemical signals from damaged tissue)
2. The phagocyte recognises the pathogen's non-self antigens
3. The phagocyte engulfs the pathogen by endocytosis, forming a phagosome
4. Lysosomes fuse with the phagosome, forming a phagolysosome
5. Hydrolytic enzymes from the lysosomes digest the pathogen
6. The phagocyte presents the pathogen's antigens on its surface (becomes an antigen-presenting cell or APC) — this is crucial for activating the specific immune response

T Lymphocytes — Cell-Mediated Immunity

T lymphocytes (T cells) mature in the thymus gland and respond to cells presenting foreign antigens.

1. An antigen-presenting cell (e.g., macrophage) presents the pathogen's antigen on its surface
2. A T helper cell ($CD4^+$) with a complementary receptor binds to the antigen
3. The T helper cell is activated and releases cytokines (chemical signals) that:
   • Stimulate B cells to divide and produce antibodies
   • Stimulate T killer cells to destroy infected cells
   • Stimulate phagocytes to be more active
4. T killer cells ($CD8^+$, cytotoxic T cells) destroy infected body cells by releasing perforin (creates pores in the cell membrane) and granzymes (trigger apoptosis/programmed cell death)
5. T memory cells are produced for long-term immunity

B Lymphocytes — Humoral Immunity

B lymphocytes (B cells) mature in the bone marrow and produce antibodies.

1. Each B cell has specific antibody receptors on its surface
2. When a B cell encounters a pathogen with a matching antigen, and receives signals from a T helper cell, it is activated
3. The activated B cell undergoes clonal expansion — rapid division by mitosis to produce many identical B cells
4. These differentiate into:
   • Plasma cells: Secrete large quantities of antibodies (immunoglobulins) into the blood and lymph
   • B memory cells: Long-lived cells that remain in the body for rapid response on re-exposure

Clonal Selection Theory

• The body produces millions of different B cells during development, each with a unique antibody receptor
• When a specific antigen enters the body, only the B cell with the matching receptor is selected and activated
• This selected B cell proliferates (clonal expansion) to produce many identical cells

Antibodies (immunoglobulins) are Y-shaped glycoproteins with a specific structure:

• Two heavy chains and two light chains held together by disulfide bonds
• Variable region: The tips of the Y — unique for each antibody, forming the antigen-binding site (complementary to one specific antigen)
• Constant region: The stem of the Y — the same in all antibodies of one class; determines how the antibody works (e.g., activating complement, binding to phagocytes)
• Hinge region: Allows flexibility for the two binding sites to bind antigens at different angles

How Antibodies Work

1. Agglutination: Antibodies bind to antigens on multiple pathogens, clumping them together → easier for phagocytes to engulf
2. Neutralisation: Antibodies bind to toxins or pathogen surface proteins, preventing them from affecting host cells
3. Opsonisation: Antibodies coat the pathogen, making it more recognisable to phagocytes
4. Complement activation: Antibody-antigen complex triggers the complement system (proteins that form pores in pathogen membranes)

• A vaccine contains dead, attenuated (weakened), or fragments of a pathogen
• The antigens stimulate a primary immune response without causing disease
• Memory cells (B and T) are produced
• On re-exposure, the secondary immune response is faster, stronger, and longer-lasting

Types of Immunity

• Active immunity: Body produces its own antibodies and memory cells (long-lasting)
• Passive immunity: Antibodies provided from another source (short-lived — no memory cells)

Monoclonal antibodies are identical antibodies produced from a single clone of B cells.

Production

1. Inject an animal (e.g., mouse) with the target antigen
2. Collect B cells from the animal's spleen
3. Fuse B cells with myeloma (cancer) cells to create hybridoma cells
4. Hybridomas are immortal (divide indefinitely) and produce antibodies
5. Select and clone the hybridoma producing the desired antibody
6. Grow in culture to produce large quantities of identical antibodies

Uses

• Pregnancy tests: Detect hCG hormone in urine
• Diagnosis: ELISA tests, blood typing, detecting specific diseases
• Cancer treatment: Antibodies bind to tumour-specific antigens; can carry drugs or radioactive markers directly to cancer cells
• Research: Locating specific molecules in cells and tissues

Question: Describe the role of T helper cells in the specific immune response. (5 marks)

Solution:

T helper cells have specific receptors that bind to antigens presented on the surface of antigen-presenting cells (such as macrophages). When the T helper cell receptor is complementary to the presented antigen, the T helper cell is activated. It then releases cytokines — chemical signals that stimulate other immune cells. Cytokines stimulate B cells to undergo clonal expansion and differentiate into plasma cells (which produce antibodies) and memory cells. They also activate T killer cells to destroy infected body cells. Additionally, cytokines enhance the activity of phagocytes. T helper cells are therefore central coordinators of the specific immune response.

• Antigens trigger immune responses; self-antigens are tolerated, non-self antigens are attacked.
• Phagocytosis provides non-specific defence; phagocytes become antigen-presenting cells to activate specific immunity.
• T cells (cell-mediated): T helpers coordinate the response via cytokines; T killers destroy infected cells.
• B cells (humoral): undergo clonal expansion → plasma cells (antibodies) and memory cells.
• Antibodies are Y-shaped proteins with variable regions that bind specific antigens.
• Vaccines stimulate primary immune response and memory cell production; monoclonal antibodies are lab-produced identical antibodies.