Innate immunity
Also known as: innate immune system, non-specific immunity, natural immunity, native immunity, first line of defence, first line of defense
The inborn, rapid (minutes–hours) first line of defence — barriers, phagocytes, NK cells, complement, cytokines and inflammation — which recognises conserved microbial patterns with germline-encoded receptors and responds the same way at every encounter.
Overview
Innate defences are present before infection and act immediately. Barriers form the first line: physical (keratinised stratified epithelium of the skin, epithelial tight junctions, mucus, the mucociliary escalator, flushing by tears, saliva and urine, coughing and sneezing), chemical (acidic skin surface pH ≈ 5 and sebum fatty acids, gastric acid pH 1–3, lysozyme in tears and saliva, antimicrobial peptides such as defensins and cathelicidin, surfactant proteins) and biological (the commensal microbiota, which competes with pathogens — "colonisation resistance").
If barriers are breached, the second line takes over: phagocytes (neutrophils, monocytes/macrophages, dendritic cells), NK cells and other innate lymphoid cells, mast cells, eosinophils and basophils; soluble defences — the complement system, acute-phase proteins (C-reactive protein, mannose-binding lectin, serum amyloid A), interferons and other cytokines; and integrated responses — inflammation and fever. Recognition relies on pattern-recognition receptors that detect PAMPs and DAMPs, so innate immunity distinguishes infectious non-self from self but has limited specificity and no classical memory (although "trained immunity", an epigenetic reprogramming of monocytes after BCG vaccination or infection, provides some non-specific enhanced responsiveness).
Crucially, innate immunity also instructs adaptive immunity: dendritic cells activated through PRRs carry antigen to lymph nodes and provide co-stimulation and cytokines; complement fragment C3d enhances B-cell activation. In return, adaptive immunity recruits innate effectors — antibodies direct complement, phagocytes and NK cells, and Th1 cells activate macrophages.
Parts & subdivisions
- Skin and mucosae, mucus and cilia, acid, lysozyme, defensins, commensal microbes.
- Neutrophils (first wave), macrophages (resident sentinels and second wave), dendritic cells (antigen presenters).
- Kill virus-infected and tumour cells; produce IFN-γ.
- Opsonisation, inflammation, lysis.
- TLRs, NLRs, RLRs and lectins that detect PAMPs and DAMPs.
- Integrated tissue and systemic reactions mediated by cytokines.
- Type I interferons create an antiviral state in neighbouring cells.
Function
- Prevent microbial entry (barriers).
- Contain and kill microbes within minutes to hours of entry.
- Remove dead cells and debris and start tissue repair.
- Activate and shape the adaptive immune response.
Clinical significance
Breached barriers
Burns, intravenous catheters, surgical wounds and eczema allow skin organisms in; impaired mucociliary clearance (cystic fibrosis, primary ciliary dyskinesia, smoking) causes recurrent chest infections; reduced gastric acid (proton-pump inhibitors) and antibiotic disruption of the microbiota predispose to enteric infection, including Clostridioides difficile.
Innate immunodeficiencies
Phagocyte defects (chronic granulomatous disease, leukocyte adhesion deficiency, severe congenital neutropenia) cause bacterial and fungal infections with poor pus formation or abscesses; complement deficiencies cause neisserial or encapsulated-bacterial infections and lupus-like disease.
Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.