10.2 The Innate Immune system

Overview

  • The non-specific immune system, also known as innate immunity, is the body’s first line of defence against pathogens. It provides immediate, non-specific protection against a broad range of invaders without the need for prior exposure

Anatomical barriers

Skin

  • The epidermis forms a physical barrier against pathogens

  • It consists of dead, keratinised cells that are impermeable and continuously shed to remove microbes.

  • Sebum secreted by sebaceous glands maintains a pH of 3-5, inhibiting microbial growth

  • Langerhans cells, macrophages, and intraepithelial lymphocytes are present to combat pathogens

Mucous membranes

  • Line all body cavities exposed to the external environment, including the respiratory, gastrointestinal, urogenital tracts and conjunctivae

  • Composed of:

    • Mucus: Produced by goblet cells, traps microbes with high viscosity

    • Cilia: Hair-like projections that propel mucus and trapped microbes out of the respiratory and gastrointestinal tracts.

Commensal microbes

  • These beneficial microorganisms outcompete pathogens for nutrients and space

  • They digest dietary fibres to produce substances required for a healthy colon such as metabolites, vitamins, short chain fatty acids.

  • They also release antimicrobial substances like lactic acid and bacteriocins

Soluble barriers

Antimicrobial peptides

  • Cationic proteins that disrupt microbial membranes

  • Produced by keratinocytes, mucosal epithelium, neutrophils, and macrophages

  • Example: Definsins that bind and disrupt bacterial membranes

Complement system

  • A cascade of proteins that enhances immune responses

  • Pathways:

    • Classical pathways: Recognises antibody-antigen complexes

    • Alternative pathway: Activates on microbial surfaces

    • Lectin pathway: Binds to sugar residue on bacterial surfaces

  • Functions:

    • Opsonisation: Coats pathogens to enhance phagocytosis

    • Inflammatory response: Triggers inflammation and recruits immune cells

    • Membrane attack complex (MAC): Punches holes in microbial membranes, leading to cell lysis

Opsonins

  • Soluble proteins that tag microbes, making them more recognisable for phagocytes

  • Example: C3b from the complement system binds to pathogens for enhanced phagocytosis

Cellular barriers

Macrophages

  • Professional phagocytes that engulf and digest pathogens

  • Reside in tissues and act as antigen-presenting cells (APCs)

Neutrophils

  • Detect and destroy virus-infected cells and tumor cells by inducing apoptosis

  • Recognise cells that lack MHC I markers, a sign of infection of abnormality

Basophils and mast cells

  • Involved in inflammatory responses and release histamine during allergic reactions

Phagocytosis and apoptosis mechanisms

Phagocytosis

  • The process of engulfing pathogens by microphages and neutrophils

  • Steps:

    1. Recognition: Microbes are identified by pattern recognition receptors (PRRs) or opsonins like C3b.

    2. Engulfment: The pathogen is internalised into a phagosome

    3. Digestion: Phagosome fuses with lysosomes to form a phagolysosome, where enzymes break down the pathogen

Apoptosis

  • Controlled cell death induced by natural killer cells

  • Infected or damaged cells are triggered to self-destruct, preventing the spread of infection

  • Apoptotic bodies are formed and safely removed by phagocytes without causing inflammation