Immune System (Part I: Innate Immune System)

Parts of the Immune System

  • Innate or Nonspecific System

    • External body membranes (skin and mucosae)
      • Prevents physical entry of microorganisms.
      • First line of defense.
    • Phagocytes, antimicrobial proteins, inflammation
      • Activated by chemical signals when external defenses are penetrated.
      • Second line of defense.

  • Adaptive or Specific System

    • Main components are the B and T lymphocytes.
      • B-lymphocytes: Humoral or antibody-mediated immunity.
      • T-lymphocytes: Cellular or cell-mediated immunity.
    • Takes considerable time but is highly specific.
      • Third line of defense.

  • Functional System

    • Organs involved in the immune response with trillions of individual immune cells.
    • Confers immunity, which is resistance to disease.

Innate Defenses

  • Function

    • Combat pathogens (harmful or disease-causing microorganisms).
    • In a state of readiness, responds within minutes to protect from ALL foreign substances.

  • Surface Barriers

    • Skin
      • Physical barrier.
      • Heavily keratinized epithelial membrane.
      • Resistant to most weak acids, weak bases, bacterial enzymes, and toxins.
      • Secretions are acidic (pH 3-5), inhibiting bacterial growth.
      • Sebum contains chemicals toxic to bacteria.
    • Mucous Membranes
      • Lines all body cavities open to the exterior (digestive, respiratory, urinary, and reproductive tracts).
      • Stomach secretes HClHCl and protein-digesting enzymes to kill microorganisms.
      • Saliva and lacrimal fluid contain lysozyme which destroys bacteria.
      • Sticky mucus traps microorganisms in digestive and respiratory passageways.
      • Structure modifications (mucus-coated hairs and ciliated mucosa) trap and sweep particles away from lower respiratory passages.
    • Breaching Surface Barriers
      • When surface barriers are breached by small nicks or cuts microorganisms invades deeper tissues and the internal innate defenses become important

  • Internal Defenses

    • Nonspecific, consisting of phagocytes, natural killer cells, antimicrobial proteins, fever, and the inflammatory response (macrophages, mast cells, all types of white blood cells).

    • Phagocytes

      • Cells that engulf or "eat" pathogens.
      • Mainly macrophages.
        • Derived from monocytes which leave the bloodstream and enter tissue and enlarge.
        • Roam tissues searching for debris or "foreign invaders" (alveolar macrophages in the lungs, dendritic cells of the epidermis, or microglia of the brain).
        • Can be fixed (Kupffer cells in the liver).
      • Neutrophils
        • Most abundant type of white blood cell.
        • May become phagocytic upon exposure to infectious material.
        • Secrete defensins (antibiotic-like chemicals).
        • Can release oxidizing and bleach-like chemicals to destroy cells, including themselves.
        • Prolonged activity may cause normal tissues to become cancerous.
      • Eosinophils
        • Weak phagocytes but important against parasitic worms.
        • Discharges destructive contents of cytoplasmic granules.
      • Mast cells
        • Involved in allergies but have some phagocytic capabilities.

    • Mechanism of Phagocytosis

      • Ameoba-like digestion
        • Phagocyte engulfs particle using flowing cytoplasmic extensions.
        • Particle enclosed within a membrane-lined vacuole called a phagosome.
        • A lysosome fuses with the phagosome to form a phagolysosome.
        • Pathogen killed and digested within the phagolysosome.
        • Indigestible waste removed by exocytosis.
      • Requires adherence of the particle to the phagocyte.
        • Carbohydrate signatures.
        • Pneumococcus has a capsule which makes adherence difficult.
        • Opsonization (coating of foreign particles with complement proteins and antibodies) increases adherence.
      • Some pathogens can survive lysosomal enzymes and can multiply within the vacuole.
        • Respiratory burst can be activated by adaptive immune system that produce free radicals, like nitric oxide, which can kill cells.

    • Natural Killer Cells

      • In the blood and lymph.
      • Can kill and lyse cancer cells and virus-infected body cells.
      • Belong to the group large granular lymphocytes.
      • Recognize surface sugars but are fairly nonspecific.
      • Not phagocytic, but release cytolytic chemicals called perforins.
      • Secrete chemicals that enhance the inflammatory response.

    • Inflammation

      • Triggered by body tissue injuries (physical trauma, heat, irritating chemicals, infection by viruses, fungi, and bacteria).
      • Functions:
        • Prevents spread of damaging agents.
        • Disposes of cell debris and pathogens.
        • Sets the stage for repair processes.
      • Signs: redness, heat, swelling, pain, and sometimes impairment of function.
      • Begins with the release of inflammatory chemicals (inflammatory mediators) into the extracellular fluid.
        • Can come from injured tissue cells, phagocytes, lymphocytes, mast cells, and blood proteins.
      • Main inflammatory mediators: histamine, kinins, prostaglandins, complement, and cytokines.
        • Cause vasodilation and hyperemia (congestion with blood), responsible for redness and heat.
        • Increase permeability of local capillaries.
          • Fluid containing proteins (clotting factors and antibodies), called exudates, flows from the bloodstream into tissue spaces.
          • Local edema occurs and pain is triggered.
      • Edema can be beneficial
        • Helps to dilute harmful substances.
        • Brings in large quantities of oxygen and nutrients needed for repair.
        • Allows entry of clotting proteins which forms a fibrin mesh that prevents the spread of harmful agents.
      • Increases the production of b-defensins, antibiotic-like chemicals.

    • Phagocyte Mobilization

      • Sequence: mast cells à neutrophils à macrophages
      • Leukocytosis is first, and chemicals called leukocytosis-inducing factors are released from injured cells to promote neutrophil release from red bone marrow.
      • Margination is the process of cell adhesion molecules (CAMs) of neutrophils binding to cell adhesion molecules (CAMs) called selectins of the endothelial cells of capillary walls causing the neutrophils to cling to the capillary wall.
      • Diapedesis is the process of neutrophils emigrating through the capillary walls to the site of inflammation.
      • Chemotaxis is the attraction of neutrophils and other white blood cells to the site of injury due to inflammatory chemicals called chemotactic agents.
      • Monocytes become macrophages about 8-12 hours after entering the tissues. Macrophages are dominant at sites of chronic inflammation.

    • Pus is a mixture of dead or dying neutrophils, broken-down tissue cells, and living and dead pathogens.

    • Abscesses are sacs of pus walled off by collagen fibers.

    • Infection granulomas are tumorlike growths containing macrophages infected by pathogens "hiding" within it surrounded by uninfected macrophages and an outer fibrous capsule.

    • Antimicrobial proteins