The Immune System — Cells & Defence

When a pathogen breaches the physical barriers, the innate immune system responds immediately. Neutrophils — the first to arrive: Neutrophils are the most abundant white blood cell (~60–70% of all white cells). They are fast, aggressive, and arrive at an infection site within minutes. They kill bacteria by: - Phagocytosis — engulfing and digesting bacteria in lysosomes - Releasing toxic chemicals — such as reactive oxygen species (ROS) - Forming neutrophil extracellular traps (NETs) — nets of DNA that trap and kill bacteria Neutrophils are short-lived — they die at the infection site, forming pus (pus is mostly dead neutrophils). Macrophages — the clean-up crew and commanders: Macrophages (from Greek: "big eaters") are found in virtually every tissue. They: - Phagocytose pathogens, dead cells, and debris - Present fragments of the pathogens to T cells (linking innate to adaptive immunity — see below) - Release cytokines — chemical signals that orchestrate the immune response Natural killer (NK) cells: NK cells patrol the body looking for cells that have been infected by viruses or have turned cancerous. They kill these cells without needing to recognise a specific antigen — they detect the absence of normal "self" markers (MHC class I molecules) on infected or cancerous cells. The inflammatory response: When tissue is damaged or infected, the innate immune response triggers inflammation: - Blood vessels dilate and become more permeable → more blood arrives → redness, heat, swelling - Immune cells flood the area → pain from pressure on nerve endings - Fever — cytokines (especially IL-1, IL-6, TNF) signal the hypothalamus to raise body temperature. Mild fever is actually beneficial — it speeds immune cell activity and slows bacterial growth.

The adaptive immune system is remarkable — it can generate over 10 billion different receptor configurations, allowing it to recognise virtually any antigen (foreign molecule) it might encounter. Key cell types: T lymphocytes (T cells) — produced in bone marrow, mature in the Thymus: T cells have receptors (TCRs) that recognise specific antigens presented on the surface of other cells. - Helper T cells (CD4⁺) — the commanders. Activated by macrophages presenting antigen → release cytokines that activate B cells and cytotoxic T cells. HIV infects and destroys helper T cells — which is why AIDS patients are vulnerable to many infections (the commander of the immune system is killed). - Cytotoxic T cells (CD8⁺) — the killers. They identify and destroy body cells that have been infected by viruses or have become cancerous. - Regulatory T cells — prevent the immune system from attacking the body's own cells. Failure of regulatory T cells → autoimmune disease. - Memory T cells — long-lived cells that remain after an infection clears, providing rapid response on re-exposure. B lymphocytes (B cells) — mature in the Bone marrow: B cells make antibodies — Y-shaped proteins that bind to specific antigens. When a B cell encounters its matching antigen (and receives help from Helper T cells), it multiplies and differentiates into plasma cells — antibody-secreting factories that produce millions of antibodies per second. Antigen Presenting Cells (APCs): Macrophages and dendritic cells engulf pathogens, break them into fragments, and display them on their surface using MHC molecules (Major Histocompatibility Complex) — like showing a "Wanted poster" to T cells. This is the critical link between innate and adaptive immunity.

Antibodies (immunoglobulins) are Y-shaped proteins produced by plasma cells. Each antibody has a specific antigen-binding site — perfectly shaped to bind to one particular antigen (like a lock and key). How antibodies defend: - Neutralisation — antibodies bind to pathogens (or their toxins) and physically block them from attaching to host cells. A neutralised virus cannot infect cells. - Opsonisation — antibodies coat a pathogen, flagging it for phagocytosis by macrophages and neutrophils. Opsonised bacteria are much more efficiently killed. - Complement activation — antibody binding can activate the complement system — a cascade of proteins that punch holes in bacterial membranes (the membrane attack complex), directly killing bacteria. - Agglutination — antibodies can bind multiple pathogens together, forming clumps that are more easily phagocytosed. Five types of antibodies (immunoglobulin classes): - IgG — the most abundant; crosses the placenta to protect newborns; main antibody of secondary immune response - IgM — first antibody produced in a new infection; very large pentamer structure - IgA — found in secretions (saliva, breast milk, mucus) — protects mucosal surfaces - IgE — involved in allergic responses; also fights parasites - IgD — function still being studied; acts as a B cell receptor Immunological memory — the key to vaccination: After fighting an infection, some T and B cells become long-lived memory cells. On re-exposure to the same pathogen, these memory cells mount a faster, stronger, and more targeted response — the secondary immune response. The pathogen is eliminated so quickly that no symptoms develop — you are immune. Vaccination exploits this by exposing the immune system to a harmless version of the pathogen (or just its antigens) — training the memory response without causing disease. The second dose in many vaccine schedules is specifically to boost and consolidate memory cell formation.

The immune system is powerful — which means when it misfires, the consequences can be serious. Autoimmune disease — attacking self: Normally, T cells that recognise self-antigens are eliminated during development in the thymus (a process called negative selection). When this fails, or regulatory T cells are insufficient, the immune system attacks the body's own tissues: - Type 1 diabetes — immune destruction of beta cells in the pancreas → no insulin production - Rheumatoid arthritis — immune attack on joint synovium → chronic inflammation and joint destruction - Multiple sclerosis — immune attack on myelin sheaths of neurons → neurological symptoms - Systemic lupus erythematosus (SLE) — widespread autoantibodies attacking multiple organs Treatment often involves immunosuppressant drugs — but these increase infection risk. Allergies — overreacting to harmless things: An allergy is an immune response to a harmless substance (an allergen — pollen, nuts, cat dander). The first exposure sensitises the immune system, producing IgE antibodies. On re-exposure, IgE triggers mast cells to release histamine and other chemicals → sneezing, itching, swelling, bronchoconstriction. Antihistamines block histamine receptors. Anaphylaxis is a life-threatening extreme allergic reaction — massive histamine release causes airway swelling and circulatory collapse → treated with adrenaline (epinephrine). Immunodeficiency — not enough immunity: - Primary — genetic (e.g. severe combined immunodeficiency, SCID — "bubble boy disease") - Secondary — acquired (HIV/AIDS; chemotherapy; immunosuppressant drugs after organ transplants) With immunodeficiency, infections that healthy immune systems clear easily become life-threatening (opportunistic infections). Cancer immunotherapy: The immune system can recognise and kill some cancer cells — but tumours have evolved ways to evade immune detection. Modern checkpoint inhibitors (like pembrolizumab, nivolumab) release the brakes on T cells, allowing them to attack tumour cells again. This has transformed outcomes in some previously untreatable cancers — a Nobel Prize was awarded for this discovery in 2018.