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Chapter 16: Innate Immunity: Non-Specific Defenses of The Host

Chapter 16: Innate Immunity: Non-Specific Defenses of The Host

The Concept of Immunity

  • Immune System: Protects the human host from pathogens.

  • Immunity: Ability to fight off pathogens and prevent disease.

  • Host Resistance vs Host Susceptibility:

    • Host Resistance: The state of having immunity.

    • Host Susceptibility: The state of lacking immunity (lacking resistance).

  • Host Defense: Ability of the host to remove pathogens and prevent disease.

    • If host defenses (immune responses) are successful, the host has immunity (resistance).

    • If host defenses are NOT successful, the host becomes diseased (susceptibility).

Two Types of Defenses (Immunity):

  1. Innate Immunity

  2. Adaptive Immunity

Innate Immunity

  • Present from birth; babies have this type of immunity against any pathogen (non-specific).

  • Characteristics:

    • Aka “non-specific” immunity: does not discriminate among pathogens (not picky).

    • No specific recognition of microbes.

    • Rapid immune response.

    • Composed of the 1st and 2nd Lines of Host Defenses.

Adaptive Immunity

  • Develops later to handle specific microbes; NOT present at birth.

  • Characteristics:

    • Immunity or resistance to specific pathogens; only certain pathogens are targeted.

    • Discriminates among pathogens (specific immunity).

    • Has immunological memory (immune system has encountered the same pathogen before).

    • Slower immune response compared to innate immunity, but still fast.

    • Composed of the 3rd Line of Host Defenses.

Structure of Host Defenses

  1. Innate Immunity (Non-Specific Host Defenses)

    • 1st Line of Defense:

      • Physical Barriers

      • Chemical Barriers

      • Biological Barriers

    • 2nd Line of Defense:

      • Formed Elements

      • Phagocytosis

      • Inflammation

      • Fever

      • Antimicrobial Substances

  2. Adaptive Immunity (Specific Host Defenses)

    • Humoral Immunity

    • Cell-mediated Immunity

1st Line of Host Defense: Physical Barriers

  • Intact Skin:

    • Non-broken skin with closely packed epithelial cells (flat/tight squamous).

    • Continuous layering (multiple layers at epidermis).

    • Keratin Protein: In top layer, reinforces skin, protecting underlying layers (epidermis).

    • Dryness: Lack of moisture deters pathogens.

    • Shedding of Top Layer: Helps to remove pathogens.

  • Mucous Membranes:

    • Line all body cavities (gastrointestinal, respiratory, genitourinary tracts).

    • Secretes viscous fluid (mucus) which traps pathogens, facilitating removal.

  • Ciliary Escalators:

    • Present in lower respiratory tract (epithelial cells with cilia move mucus out of the body).

    • Functions as a flushing mechanism (via coughing or swallowing).

  • Lacrimal Apparatus:

    • Protects the eyes through tears, which continuously wash and remove pathogens.

  • Saliva, Urine, and Vaginal Secretions:

    • Flushing mechanisms that help prevent accumulation of pathogens.

1st Line of Host Defense: Chemical Barriers

  • Chemical Factors in the Skin:

    • pH of Skin: Slightly acidic, most bacteria dislike acidic conditions.

    • Salinity: Most bacteria are NOT halophiles; salty environment helps kill bacteria.

  • Lysozymes:

    • Enzymes in body secretions (sweat, tears, saliva) that break down peptidoglycan, destroying bacterial cell walls.

  • Gastric Juices:

    • Produced by the stomach, containing enzymes and acid that destroy most bacteria (except acidophiles).

  • Transferrin in Blood:

    • Proteins that bind to iron (Fe), removing it, thus limiting bacterial growth.

1st Line of Host Defense: Biological Barriers

  • Normal Microbiota: Beneficial bacteria that do not harm the host.

    • Commensal Microbes: Benefit themselves without harmful effects to the host.

    • Beneficial Microbes: Microbes that provide benefits to the host (e.g., Vitamin K-producing bacteria in gastrointestinal tract).

    • Opportunistic Microbes: Microbes that act as pathogens if they are in the wrong environment (e.g., E.coli in the urethra).

    • Competitive Exclusion:

    • Microbial Competition: Normal microbiota compete with pathogens, decreasing pathogenic bacteria populations.

    • Methods of competition include:

      1. Nutrient acquisition (normal microbiota consuming nutrients, leaving none for invaders).

      2. Space occupation (normal microbiota occupying space preventing invaders from colonizing).

      3. Production of harmful substances to pathogens.

2nd Line of Host Defense: Components

  1. Formed Elements in Blood:

    • Comprise cells and cell fragments suspended in plasma:

      • Erythrocytes: Red blood cells containing hemoglobin (binding oxygen).

      • Leukocytes: White blood cells involved in immune function.

      • Thrombocytes: Cell fragments from megakaryocytes involved in blood clotting.

    • Created in red bone marrow through hematopoiesis.

  2. Types of Leukocytes:

    • Granulocytes (BEN): Leukocytes with granules in cytoplasm visible under a microscope.

      • Basophils: Release histamine; involved in allergic responses.

      • Eosinophils: Toxic against parasites and worms.

      • Neutrophils: Phagocytic; the first responders to infection.

    • Agranulocytes: Leukocytes without visible granules under a microscope.

      • Monocytes: Travel in blood and mature into macrophages in tissues.

      • Lymphocytes:

      • T cells (adaptive immunity).

      • B cells (adaptive immunity).

      • Natural Killer (NK) cells.

    • Differential White Blood Cell Count: Measures the abundance of each type of white blood cell in a sample of 100 white blood cells in a normal state.

      • From least to most common: Never Let Monkey Eat Bananas.

      • Neutrophils

      • Lymphocytes

      • Monocytes

      • Eosinophils

      • Basophils

  3. Phagocytosis:

    • Definition: Ingestion (engulfment) of microbes or other substances by a phagocyte.

    • Examples of Phagocytes:

      • Neutrophils (first responders), macrophages (tissues), dendritic cells (skin).

    • Mechanisms/Phases of Phagocytosis:

    1. Chemotaxis: Chemical signals (cytokines) released by pathogens attract phagocytes.

    2. Adherence: Binding of phagocyte to the pathogen surface.

    3. Ingestion: Endocytosis of the pathogen, forming a phagosome which merges with a lysosome.

    4. Digestion: The pathogen is digested inside the phagolysosome.

    • Microbial Evasion of Phagocytosis:

      • Pathogens may evade phagocytosis through:

      • Capsule: Large size prevents engulfment (e.g., Streptococcus pneumoniae).

      • Leukocidins: Pore-forming toxins that kill phagocytes (e.g., Staphylococcus).

      • Mycolic Acid: Waxy lipid in cell walls that inhibits lysosomal enzymes, allowing bacteria to multiply within phagocytes (e.g., Mycobacterium).

  4. Inflammation:

    • Aim: To eliminate pathogens and initiate tissue healing with neutrophils and macrophages.

    • Signs and Symptoms:

      • Pain: Due to cytokines released by leukocytes damaging nerve endings.

      • Redness (Erythema): Increased blood flow to the affected area.

      • Immobility: Local loss of function due to tissue damage.

      • Swelling (Edema): Accumulation of fluid outside blood vessels.

      • Heat: Due to increased blood flow.

    • Process of Inflammation:

    1. Tissue damage/infection occurs.

    2. Damaged cells release chemicals (cytokines).

    3. Cytokines promote chemotaxis of phagocytes to the injury site.

    4. Phagocytes like neutrophils squeeze through blood vessels to access damaged tissue.

    5. Phagocytosis of pathogens occurs.

    6. Tissue is repaired.

  5. Fever:

    • Caused by bacterial infection; reactions include:

    1. Bacterial toxins induce cytokine release from phagocytes.

    2. Cytokines bind receptors in the hypothalamus, raising the body’s temperature set point.

    3. The elevated temperature induces chills, making the individual feel cold as they heat up.

    4. High body temperature (fever) prevents pathogen proliferation.

    5. As pathogens are eliminated, toxins and cytokines are cleared, resetting the body’s thermostat.

    • Consequences of Fever:

      • Increases metabolic rate (more ATP production).

      • Enhances immune response (increased activity of phagocytes).

  6. Induction of Antimicrobial Substances:

    • Certain cells release proteins that help destroy pathogens.

    • Examples:

    1. Complement System: Enhances the immune system in destroying pathogens.

      • Involves an activation cascade of complement proteins (inactive to active state).

      • Outcomes of Complement Activation:

        1. Opsonization: Complement proteins coat pathogen surfaces to enhance phagocyte attachment.

        2. Inflammation: Binding of complement proteins to mast cells releases histamine, increasing blood vessel permeability to allow phagocytes access.

        3. Cytolysis: Membrane attack complex (MAC) formation, creating holes in pathogen membranes, leading to pathogen death (bursting).

      • Microbial Evasion of the Complement System:

        • Capsule production hindering complement binding.

        • Inhibition of MAC formation through bacterial enzymes.

        • Bacteria may also produce proteases to degrade complement proteins.

    2. Interferons (IFNs): Small proteins released by virus-infected cells to protect neighboring uninfected cells.

      • Mode of Action:

        1. Virus infects a host cell.

        2. The infected cell produces and releases IFNs.

        3. IFNs bind neighboring uninfected cells, prompting them to produce antiviral proteins (AVPs).

        4. Newly infected cells are now ready to combat virus entry due to these AVPs.