10.1 Barriers, Clotting and Innate Immunity

Unbroken skin is both a physical and chemical barrier. Its outer keratinized layers are difficult to penetrate, continuously shed cells and limit water movement. Sebum contributes lipids and an environment that inhibits many bacteria, while slightly acidic sweat discourages growth. These properties are non-specific because they do not depend on recognizing a particular pathogen. A cut matters immunologically because it bypasses several defences at once and gives microorganisms direct access to nutrient-rich tissue and blood.

Internal exchange surfaces cannot be covered by dry keratinized tissue, so openings are protected differently. Mucous membranes line the respiratory, digestive, urinary and reproductive tracts. Mucus traps particles and microorganisms; cilia in much of the airway move contaminated mucus toward the throat. Tears, saliva and mucus contain lysozyme, which catalyses hydrolysis of bonds in bacterial peptidoglycan, and phospholipases can disrupt bacterial membranes. The stomach's low pH kills many swallowed organisms, although acid-tolerant pathogens may survive.

Barrier descriptions earn explanatory value only when structure is linked to consequence. Mucus without clearance could become a reservoir; ciliary action makes trapping useful. A waterproof epidermis blocks entry but cannot perform pulmonary gas exchange; a thin alveolar surface therefore depends on mucus, resident immune cells and coordinated clearance instead. Defences reflect a trade-off between exclusion and the physiological work that a surface must perform.

The agents that challenge these surfaces differ. Bacteria such as those causing tuberculosis and cholera reproduce as prokaryotic cells; pathogenic fungi can colonize keratinized or moist surfaces; protoctists such as Plasmodium live as parasites; and multicellular worms may persist in tissues or the gut. Viruses must enter compatible host cells to reproduce. A barrier can reduce exposure to all of them, but later control must account for whether the target is extracellular, intracellular or too large to be engulfed by one phagocyte.

When a small blood vessel is damaged, exposed tissue and activated platelets initiate a cascade of clotting reactions. Platelets adhere at the damaged surface and release factors that promote further platelet activation. Clotting factors convert inactive prothrombin into the protease thrombin. Thrombin then converts soluble fibrinogen into insoluble fibrin. Long fibrin threads form a mesh that traps erythrocytes and other cells, producing a clot that limits blood loss and pathogen entry.

A cascade provides amplification: one activated enzyme can activate many molecules at the next step, so a small local signal rapidly produces a large fibrin network. The components normally circulate in inactive forms because widespread activation would obstruct vessels. Restricting activation to damaged tissue is therefore as important as activating it quickly. When exposed at the surface, the clot dries to form a scab while repair proceeds beneath it; the scab is a temporary barrier, not newly formed skin.

Damaged tissue, basophils and mast cells can release histamine. Histamine relaxes smooth muscle in local arterioles, increasing blood flow, and increases capillary permeability by changing connections between endothelial cells. More plasma and leucocytes can then leave the blood and enter affected tissue. Increased flow contributes to redness and warmth; fluid accumulation causes swelling; chemical mediators and pressure stimulate sensory neurones, contributing to pain or itching.

Inflammation is protective when it concentrates cells and soluble molecules near damage, but its effects are not cost-free. Excess fluid can impair tissue function, and a systemic or poorly controlled response can itself be dangerous. This is a recurring principle: immune mechanisms are selected because their benefits usually exceed their costs under appropriate regulation, not because every increase in immune activity improves health.

Phagocytic leucocytes such as neutrophils and macrophages move toward chemical signals by chemotaxis. Signals may be released by pathogens, damaged cells or immune cells already at the site. Surface receptors bind molecular patterns on the target. The phagocyte changes shape, surrounds the particle with its plasma membrane and encloses it in a phagosome by endocytosis. Lysosomes fuse with the phagosome and release hydrolytic enzymes; useful products may enter the cytoplasm and indigestible residues leave by exocytosis.

Phagocytosis is innate because the same broad process removes many targets, but macrophages also connect innate and adaptive immunity. After digestion, a macrophage can display pathogen-derived peptide fragments on its surface. A compatible helper T cell can recognize the presented antigen. The phagocyte therefore both destroys material immediately and supplies information that helps select a specific response.

Self–non-self discrimination is essential. Healthy body cells display self markers and normally avoid immune attack; apoptotic cells expose signals that promote their quiet removal. A virus-infected or mutated cell may display unusual antigens and become a target for lymphocytes. Recognition is not infallible: failure to attack permits infection or cancer, while attack on healthy tissue produces autoimmune damage. The system must optimize both sensitivity and restraint.

Innate defence does not acquire antigen-specific memory in the same sense as B and T lymphocytes. Its cellular and molecular components can change in abundance during infection, but the recognition rules are broadly inherited and repeat across exposures. This is why an immediate innate response can begin during a first encounter, yet a second encounter with the same pathogen gains its decisive speed advantage from the adaptive memory established previously.