Minutes. That is how long the innate immune system needs to start responding once a germ gets in, and it can take a few hours at most. Nothing else in the body’s defences is that fast. Nothing else is as blunt, either.
The innate system responds to broad patterns on pathogens, not to a specific germ. It develops in the womb and works from inherited receptors, so it never has to learn an invader first. The flip side is that it leaves no lasting, pathogen-specific protection behind. For that the body relies on the adaptive system, which comes later. For patients and families, the innate system is the reason an infection is often contained before anyone feels ill.
Walls and secretions
The first defences are physical. Intact skin and mucous membranes line the respiratory, genitourinary and digestive tracts, and tight junctions between epithelial cells keep the barrier sealed. In the airways, cilia sweep invaders out. Harmless resident microbes help too. When that balance tips, the result can be oral thrush, bacterial vaginosis or pseudomembranous colitis.
Chemistry backs up the barriers. Gastric acid and the acidic flora of the vagina hold microbes back. Lysozyme, an enzyme made by neutrophils, granulocytes and macrophages, cuts bonds in the cell walls of certain bacteria, especially gram-positive ones. Mucus and other secretions carry both specific and nonspecific protective substances.
Lymphoid tissue sits in submucosal spots such as the gut, nasopharynx, lung, skin and conjunctiva, populated by lymphocytes, plasma cells and macrophages. In the gut it takes the form of follicles and Peyer’s patches. In the lungs, follicles appear only after infection or inflammation.
Cells on patrol
Granulocytes, natural killer cells and mast cells make up the cellular side. Phagocytes such as neutrophils and monocytes swallow pathogens. Inside, an enzyme complex called NADPH oxidase releases reactive oxygen species that destroy what has been engulfed. People born with defective NADPH oxidase develop chronic granulomatous disease. An impaired burst also raises the risk of infection with catalase-positive organisms such as Aspergillus and Staphylococcus aureus, which can break down their own hydrogen peroxide and leave the phagocyte with nothing to work with.
Eosinophils take on parasites. When they recognise a worm coated in IgE antibodies, they release major basic protein to destroy it.
Sensors and the complement cascade
Receptors on innate cells detect molecules typical of pathogens. Toll-like receptors bind pathogen-associated molecular patterns and switch on the NF-kB pathway. Intracellular NOD-like receptors pick up both those patterns and signals released by damaged host cells, and trigger proinflammatory cytokines such as IL-1 beta and IL-18. Faulty NOD2 activity has been linked to Crohn disease, sarcoidosis and graft-versus-host disease.
The fluid side of the system includes the complement proteins. The liver makes them as inactive precursors. Once triggered, by antibody complexes or by mannose on a pathogen’s surface, they set off a cascade that causes inflammation, marks bacteria for ingestion and builds the membrane attack complex. That complex punches through the wall of the target cell, which is especially effective against gram-negative bacteria. C3b and IgG are the two main opsonins for bacteria. C5a draws neutrophils to the site, and C3a, C4a and C5a can trigger mast cells, which is how anaphylaxis starts.
Doctors can read some of this from a blood sample. C-reactive protein rises during inflammation, and the CH50 test measures total complement activity. Consult your doctor for medical advice.
