Primary Non-Specific Animal Defences

Spec Mapping — OCR H420 Module 4.1.1 — Communicable diseases, content statement on the primary non-specific defences against pathogens in animals: physical and chemical barriers, blood clotting, wound repair, inflammation, expulsion reflexes, fevers and antimicrobial proteins (refer to the official OCR H420 specification document for exact wording). This lesson covers the innate immune defences that act within minutes of infection, before the adaptive response of Lessons 8–9 has time to develop.

The animal immune system operates in two broad modes: non-specific (innate) and specific (adaptive). Non-specific defences are evolutionarily ancient — homologues are found across the animal kingdom from sponges to mammals — and provide the first, rapid response to any invader. They do not discriminate between different pathogens (a Streptococcus and a Salmonella both trigger essentially the same response) but they act within minutes, do not require previous exposure, and impose a heavy first cost on any pathogen that breaches the body's surface barriers. The 2011 Nobel Prize in Physiology or Medicine, awarded jointly to Jules Hoffmann (Toll receptors in Drosophila), Bruce Beutler (Toll-like receptor 4 in mammals) and Ralph Steinman (dendritic cells), recognised the molecular basis of pattern recognition that links the innate and adaptive responses. OCR specification 4.1.1 requires you to describe the skin and mucous membranes, blood clotting and wound repair, the inflammatory response, expulsion reflexes, fevers, and the action of lysozyme and antimicrobial peptides.

Key Definitions:

• Innate immunity — non-specific, always-present defences that act rapidly against any pathogen, with no memory and no specificity beyond broad pattern recognition.
• Inflammation — the redness, swelling, heat and pain that follows tissue damage or infection, caused by local vasodilation and increased capillary permeability.
• Histamine — a small amine released by mast cells (and basophils) that triggers vasodilation and increased capillary permeability.
• Lysozyme — an enzyme that hydrolyses the β-1,4 glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine in bacterial peptidoglycan, lysing the cell wall.
• Pyrogen — a fever-inducing substance, usually a cytokine (interleukin-1) released by macrophages encountering pathogens.

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Physical Barriers

1. The Skin

The skin is the body's largest organ (~2 m² in an adult) and its most important physical barrier. The outermost layer — the stratum corneum — is composed of dead, flattened, keratinised cells (corneocytes) embedded in a hydrophobic lipid matrix that:

• Provides a thick, tough, waterproof layer impermeable to most pathogens.
• Is continuously shed (desquamation), taking attached microbes with them at a rate of ~10⁹ cells per day.
• Is replaced from below by mitotic division in the stratum basale, with cells migrating upward, terminally differentiating and dying as they go.
• Contains acidic secretions from sebaceous glands and sweat glands that lower the skin pH to ~5, an environment inhospitable to most pathogens.

The skin also supports a resident population of commensal bacteria (Staphylococcus epidermidis, Cutibacterium acnes, and others) that occupy attachment sites, consume nutrients and produce bacteriocins — collectively suppressing colonisation by pathogenic species via competitive exclusion.

The skin is breached by wounds, by injection (vaccination, needlestick injury, intravenous drug use), by burns, and by ulcers in conditions such as venous insufficiency and diabetic neuropathy. Pressure ulcers in immobile patients and surgical wounds are the major routes for hospital-acquired skin infections, and MRSA is the dominant nosocomial pathogen at these sites.

2. Mucous Membranes

Mucous membranes line the body surfaces that open to the outside: the respiratory, digestive, urogenital and conjunctival tracts. Goblet cells secrete mucus, a sticky glycoprotein gel that traps pathogens. In the airways, ciliated epithelial cells sweep mucus (with trapped microbes) upwards to the throat to be swallowed and destroyed by stomach acid — the mucociliary escalator.

3. Tears and Saliva

Tears continually wash the surface of the eye (~1 µL/minute basal secretion), and saliva bathes the mouth (~1.5 L/day total). Both contain lysozyme (discovered by Alexander Fleming in 1922 — six years before he discovered penicillin), an enzyme that hydrolyses the β-1,4 glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine in bacterial peptidoglycan, causing gram-positive bacteria to burst osmotically. Both also contain lactoferrin (which sequesters iron away from bacteria) and secretory IgA (which we shall meet in Lesson 9), giving them a layered antimicrobial chemistry beyond pure mechanical washing.

4. Stomach Acid

Hydrochloric acid secreted by parietal cells in the gastric mucosa lowers the gastric pH to 1.5–2.0, denaturing most ingested pathogens' proteins and lysing their membranes. Patients on long-term proton-pump inhibitors (omeprazole and similar) for acid reflux have a measurably elevated risk of C. difficile colitis and travellers' diarrhoea, illustrating the protective role of gastric acidity. Helicobacter pylori — the cause of most peptic ulcers and a major risk factor for gastric cancer — survives in the stomach by secreting urease that converts urea to ammonia and CO₂, locally neutralising the acid; Marshall and Warren's discovery of H. pylori (Nobel 2005) overturned the dogma that stomach acidity sterilised the gastric environment.

5. Earwax

Cerumen is a mixture of dead skin cells, fatty acids and antimicrobial peptides secreted by glands in the external ear canal. It is hydrophobic and slightly acidic (pH ~6); it traps microbes and particles entering the canal, contains lysozyme, and is slowly extruded toward the external ear, taking debris with it.

6. Commensal Flora (Competitive Exclusion)

Beyond the structural and chemical barriers, the body hosts a vast resident microbiome — around 10¹³ bacterial cells inhabit the gut, skin, mouth and vagina. Commensal species occupy attachment sites, consume local nutrients and produce antimicrobial bacteriocins, all of which suppress colonisation by pathogenic bacteria. This phenomenon — competitive exclusion — is part of what broad-spectrum antibiotic use disrupts, explaining the high incidence of Clostridioides difficile (toxin-producing) colitis after antibiotic therapy in hospital patients.

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Blood Clotting and Wound Repair

When skin is broken, the injury site must be sealed before pathogens can enter. This is achieved by haemostasis — the coordinated arrest of bleeding through vascular contraction, platelet plug formation, and the blood clotting cascade. The cascade involves about a dozen plasma proteins (clotting factors) that activate one another in sequence, producing massive signal amplification: a single drop of damaged-tissue factor can ultimately convert grams of soluble plasma fibrinogen into a fibrin clot. Deficiencies in cascade components produce inherited bleeding disorders — haemophilia A (factor VIII deficiency, the disease that affected European royal families through Queen Victoria's daughters) and haemophilia B (factor IX deficiency, Christmas disease).

flowchart LR
    A[Injury exposes collagen] --> B[Platelets bind and release chemicals]
    B --> C[Thromboplastin released]
    C --> D[Prothrombin --> Thrombin]
    D --> E[Fibrinogen --> Fibrin]
    E --> F[Fibrin mesh traps cells]
    F --> G[Clot forms, dries into scab]

Key steps

1. Vascular spasm: damaged blood vessels constrict, reducing blood flow.
2. Platelet plug formation: platelets stick to exposed collagen, release chemicals (ADP, thromboxane) that recruit more platelets.
3. Clotting cascade: damaged cells and platelets release thromboplastin, which (in the presence of Ca²⁺ and vitamin K) converts prothrombin into thrombin. Thrombin catalyses the conversion of fibrinogen (soluble) into fibrin (insoluble fibres). The fibrin mesh traps erythrocytes and platelets, forming the clot.
4. Scab formation: as the clot dries, it contracts and hardens into a scab that protects the underlying tissue while new skin grows beneath.

Meanwhile, fibroblasts move into the wound and lay down collagen, epithelial cells divide to re-cover the wound, and macrophages clear debris.

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Inflammation

If pathogens manage to enter the tissues, a characteristic inflammatory response begins. Inflammation is a coordinated vascular, cellular and biochemical response designed to deliver immune effectors to the site of infection or injury and to wall off the damage:

1. Mast cells resident in the tissue detect pathogen-associated molecular patterns via Toll-like receptors, or are activated by complement fragments C3a and C5a, or by IgE bound to their FcεRI receptors (in allergic reactions). They release stored granule contents — histamine, heparin, proteases — and synthesise lipid mediators (prostaglandins, leukotrienes) and cytokines (TNF-α, IL-6).
2. Histamine causes vasodilation of nearby arterioles via H1 receptors on smooth muscle, increasing blood flow to the area — this produces the classic redness (rubor) and heat (calor).
3. Histamine also increases capillary permeability: post-capillary venular endothelial cells contract, opening transient gaps between them through which plasma proteins (including immunoglobulin, complement, fibrinogen) and white blood cells leak into the tissue — this produces swelling (tumor) or oedema.
4. Pressure on nerve endings from the oedema, plus direct activation of nociceptors by bradykinin and prostaglandin E₂, causes pain (dolor) — a useful behavioural signal that discourages use of the injured area.
5. Cytokines (CXCL8/IL-8 and others) attract phagocytes (neutrophils first, then monocytes that differentiate into macrophages) to the site by chemotaxis; these phagocytes engulf and digest pathogens (Lesson 7).

The classical signs of inflammation — rubor (redness), calor (heat), tumor (swelling), dolor (pain) and functio laesa (loss of function) — were catalogued by Aulus Cornelius Celsus in the first century CE; the addition of "loss of function" is attributed to Virchow in the 19th century. The biology is now well understood at the molecular level: histamine, prostaglandins, leukotrienes, complement fragments (C3a, C5a) and cytokines (TNF-α, IL-1β, IL-6) drive the changes in vasculature and the migration of phagocytes from blood to tissue.

The inflammatory cascade

flowchart TD
    A[Tissue damage or infection] --> B[Mast cells release histamine + cytokines]
    B --> C[Vasodilation of arterioles]
    B --> D[Increased capillary permeability]
    C --> E[Increased blood flow: redness + heat]
    D --> F[Plasma proteins + cells leak: oedema/swelling]
    D --> G[Phagocyte migration via diapedesis]
    F --> H[Pressure on nerves: pain]
    G --> I[Phagocytosis at infection site]
    B --> J[Complement cascade activated]
    J --> K[C3b opsonisation + MAC lysis]
    I --> L[Antigen presentation to T cells]