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Chapter 16: Non-specific Defenses of the Host (Innate Immunity)

Innate Immunity (Non-Specific Defenses)

  • Non-specific defenses: components of the immune system that do not distinguish between different pathogens; they block all foreign bodies to the host.
  • Also known as innate immunity; immunity that is acquired at birth.
  • Innate immunity is activated by host cell receptors called Toll-like receptors (TLRs).
  • Activation of TLRs can stimulate the release of cytokines.
  • Cytokines are signaling proteins involved in cell-to-cell communication; many classes exist, but the core role is communication between cells during immune responses.
  • Major host cell types involved in innate immunity include macrophages and dendritic cells.

First Line of Defense: Physical Barriers (Physical Barriers)

  • Intact skin is a primary physical barrier; the integrity of the barrier is crucial because ruptured skin provides portals of entry for pathogens.
  • The upper layer of skin contains keratin, a protective protein. A dryness factor helps resist infection because many microbes prefer moist environments.
  • Mucous membranes line many body tracts; in the respiratory tract, the mucociliary escalator protects the lower respiratory tract.
    • Goblet cells secrete mucus; cilia beat to move mucus and trapped particulates upward (mucociliary escalator).
    • Mucus acts like flypaper, trapping particulates; mucus is moved by ciliary action; average movement is about 1-3\ \text{cm/hour}, though coughing or sneezing can increase this rate.
  • Flushing actions help physically remove particulates from the body; examples include tears, saliva, urine, perspiration, vomiting, and diarrhea.

First Line of Defense: Chemical Barriers

  • Low pH as a chemical barrier: stomach pH is roughly 2-4, which denatures microbial proteins and helps inactivate microbes; stomach acidity helps prevent infection from ingested materials.
  • Skin also has a relatively low pH, typically 3-5, which inhibits growth of many microbes that cannot tolerate acidic conditions.
  • Sebum, produced by sebaceous (oil) glands, contains fatty acids that inhibit the growth of some bacteria.
  • Enzymes contribute to chemical defenses; lysozyme is abundant in tears and perspiration; amylase is found in saliva; these enzymes help break down pathogens during flushing and defense processes.
  • The defense is often a combination of flushing actions and enzymatic activity rather than a single mechanism.

Second Line of Defense: Cells, Signals, and Inflammation (Cellular and Humoral Components)

  • Leukocytes (white blood cells) are the key players in the second line of defense. They are categorized as:
    • Granulocytes (e.g., basophils)
    • Agranulocytes (e.g., lymphocytes and monocytes; monocytes become immature macrophages)
  • Phagocytosis (cells eating) is a major mechanism by which leukocytes remove foreign material. Focus examples include macrophages (though neutrophils and other leukocytes can perform phagocytosis as well).
    • Recognition: a macrophage recognizes a foreign antigen whose receptors do not match the host’s own components.
    • Engulfment: the macrophage engulfs the pathogen to form a phagosome.
    • Internalization and fusion: the phagosome fuses with lysosomes to form a phagolysosome.
    • Destruction: within the phagolysosome, enzymes (e.g., lysozyme) and other antimicrobial mechanisms act to destroy the pathogen. Lysozyme targets bacterial peptidoglycan; reactive oxygen species (oxygen radicals) can attack lipids and proteins in the pathogen; defensins disrupt microbial membranes.
    • Some pathogens resist phagocytosis (e.g., bacteria with a capsule). A capsule (glycocalyx densely joined to the bacterium) can hinder recognition by leukocytes and can reduce enzymatic degradation, allowing intracellular survival; this is a reminder that phagocytosis, while efficient, is not universally successful. A backup system exists in the adaptive (specific) immune response for such cases.
  • Macrophages also produce paracrine signals to alert other immune components of infection:
    • Interleukin-1 (IL-1)
    • Tumor necrosis factor alpha (TNF-\alpha)
    • These signals promote inflammation and recruit additional immune cells to the site of infection.

Inflammation and Tissue Repair

  • Inflammation is characterized by redness, heat, pain, and swelling at the site of infection or injury.
  • Three key steps of inflammation:
    • Vasodilation: triggered by chemical mediators (e.g., histamine); a fibrin clot often forms as part of the inflammatory response to localize the injury.
    • Phagocyte migration: margination (leukocytes adhere to the endothelium) and emigration (diapedesis) allow phagocytes to reach damaged tissue.
    • Tissue repair: damaged tissue undergoes repair processes after initial inflammation.
  • Fever can accelerate tissue repair by increasing metabolic activity and can inhibit pathogen replication since many pathogens have an optimal growth temperature range; fever can impede growth if the host’s temperature exceeds that range.

Complement System and Interferon (Non-Specific Immunity Components)

  • Complement system:
    • Comprises about 30 proteins produced mainly by the liver.
    • These proteins act in a cascade, contributing to innate and, in many cases, adaptive immunity.
    • Complement can function against extracellular antigens (with some exceptions).
  • Interferon: a signaling protein system used particularly against intracellular pathogens, especially viruses; interferons help to establish an antiviral state in neighboring cells and modulate the immune response.

Summary: Key Concepts and Connections

  • Non-specific innate immunity provides immediate defense and is activated at birth; it does not require prior exposure to a pathogen.
  • Physical barriers (skin, mucous membranes, mucociliary escalator, flushing actions) provide the first line of defense, with chemical barriers (low pH, sebum, enzymes) enhancing protection.
  • The second line of defense relies on leukocytes and soluble factors (cytokines, complement, interferon) to identify, contain, and eliminate pathogens.
  • Phagocytosis is central to pathogen clearance but can be circumvented by certain microbial defenses such as capsules; this limitation is addressed by the broader immune system, including adaptive immunity.
  • Inflammation coordinates the mobilization of immune cells, supports tissue repair, and may be accompanied by fever, which helps curb pathogen growth and facilitates repair.
  • The innate immune system provides essential early defense and sets the stage for the adaptive immune response that will provide targeted, long-lasting protection.

Real-World Relevance and Implications

  • Understanding innate defenses explains why intact skin and mucosal barriers are crucial for infection prevention (e.g., importance of hand hygiene, skin moisture balance).
  • Knowledge of how pathogens evade phagocytosis (e.g., capsule formation) informs vaccine design and antimicrobial strategies.
  • The cytokine network (e.g., IL-1, TNF-\alpha) is a key target in treating inflammatory diseases and is involved in systemic responses such as fever and acute-phase reactions.
  • The complement system and interferons are central to host defense against extracellular and intracellular pathogens, respectively, and have clinical relevance in immunodeficiencies, infections, and immunotherapies.