Exam 5 Study Guide: Innate Immune System

Exam 5 Study Guide: Innate Immune System and Other Related Topics

Chapter 16: Components of the Innate Immune System

  • Definition: The innate immune system is composed of two lines of defense.
      - First Line of Defense:
        - Functions to keep pathogens outside or neutralize them prior to infection.
        - Components:
            - Skin: The largest organ, serving as a physical barrier.
            - Mucous Membranes: Secrete mucus, produced by goblet cells, to trap pathogens.
            - Antimicrobial Secretions:
                - Urine: Flows to expel pathogens.
                - Sebum: Keeps skin moisturized and prevents brittleness.
                - Saliva: Dilutes microorganisms and washes teeth surfaces.
                - Cilia: Moves trapped particles out of the respiratory tract.
                - Diarrhea and Vomiting: Mechanisms to expel microbes from the gastrointestinal tract.
      - Second Line of Defense:
        - Functions to slow or contain infections when the first line fails.
        - Components:
            - Proteins: Involved in inflammation and fever response.
            - Phagocytes: Cells that engulf and destroy pathogens.
            - Natural Killer (NK) Cells: Attack and destroy cancerous and virus-infected cells.

Physical vs. Chemical Barriers

  • Physical Barriers:
      - Barriers to entry and processes for removing microbes.
      - Examples include:
        - Skin: Composed of dermis and epidermis.
        - Mucous Membranes: Secretes mucus to trap pathogens.
        - Lacrimal Apparatus: Produces tears to protect the eyes.
        - Saliva: Washes away microorganisms from teeth and gums.
        - Diarrhea/Vomiting: Expels pathogens from the body.

  • Chemical Barriers:
      - Substances that inhibit microbial growth.
      - Examples include:
        - Sebum: Prevents skin dryness.
        - Perspiration: Maintains body temperature, eliminates wastes, flushes microbes.
        - Gastric Juice: High acidity destroys bacteria and toxins.

Normal Bacteria and Innate Immunity

  • Function: Normal flora inhibit pathogenic bacteria.
      - Examples include:
        - Escherichia coli: Produces bacteriocins to inhibit closely related bacterial species in the large intestine.
        - Lactobacillus: Produces hydrogen peroxide in the vagina under anaerobic conditions.

Cells of the Innate Immune System

  • Mast Cells: Release chemicals that activate inflammation.

  • Neutrophils: Function in phagocytosis, removing pathogens.

  • Basophils: Produce histamine during allergic responses.

  • Eosinophils: Attack parasites; some can undergo phagocytosis.

  • Monocytes: Mature into macrophages, performing phagocytosis.

  • Dendritic Cells: Capture antigens and present them to T cells, initiating adaptive immunity.

  • Natural Killer (NK) Cells: Induce apoptosis in infected or cancerous cells.

Phagocytosis Process

  1. Chemotaxis and Adherence:
       - Chemotaxis: Attraction of phagocytes to microorganisms via microbial products, damaged tissues, and complements.
       - Adherence: Attachment of phagocyte membrane to the pathogen, facilitated by pathogen-associated molecular patterns (PAMPs) binding to TLRs on phagocytes.

  2. Ingestion:
       - Phagocyte extends pseudopods to engulf pathogen, forming a phagosome.

  3. Formation of Phagosomes.

  4. Fusion:
       - Phagosome fuses with lysosome, forming a phagolysosome.

  5. Digestion:
       - Enzymes such as lysozyme, lipases, proteases, and nucleases break down pathogens.

  6. Residual Body Formation:
       - Indigestible materials left in the phagolysosome are expelled from the cell.

Microbial Evasion Techniques

  • Capsules: Prevent phagocytosis.

  • Biofilms: Protect microbes from immune responses.

  • M Proteins: Inhibits phagocytosis.

  • Intracellular Survival: Pathogens survive inside cells.

  • Inhibition of Phagolysosome Fusion: Prevents digestion of engulfed pathogens.

Inflammation

  • Definition: Host's response to tissue damage characterized by redness, heat, pain, swelling, and potential loss of function.

  • Purpose: To destroy injurious agents and eliminate by-products; facilitate tissue repair and replacement.

  • Acute Inflammation: Rapid onset, lasts days/weeks (e.g., sore throat, flu).

  • Chronic Inflammation: Slow development, lasts months/years (e.g., peptic ulcers, rheumatoid arthritis).

  • Mechanisms:
      - Dilation of blood vessels (causing redness and heat).
      - Increased permeability (causing edema).

Fever

  • Definition: Abnormally high body temperature, a component of the third line of defense.

  • Causes: Primarily bacterial infections (by their toxins) or viral infections.

  • Hypothalamus Function: Acts as a thermostat; normal setting at 37 °C (98.6 °F).

  • Mechanism:
      - Phagocytes ingest gram-negative bacteria, releasing lipopolysaccharides (LPS).
      - LPS stimulates cytokines (IL-1, TNF-α) release, prompting the hypothalamus to produce prostaglandins.

  • Dangerous Highs: Body temperature can be lethal above 44-46 °C (112-114 °F).

Complement System

  • Definition: Collection of over 30 proteins produced by the liver, circulating in the blood.

  • Function: Complements/enhances immune system cells through microbial destruction.

  • Activation: Proteins are inactive until split into functional fragments (e.g., C3 → C3a + C3b).
      - C3a: Participates in inflammation.
      - C3b: Functions in opsonization and cytolysis.

Chapter 17: Cytokines and Immune Response

  • Cytokines: Soluble proteins produced by activated immune cells, activating nearby cells with receptors.
      - Types:
          - Interferons: Interfere with viral infections.
          - Chemokines: Induce leukocyte migration towards infection.
          - Interleukins (ILs): Communicate between leukoctyes, stimulate immune reactions.
          - Tumor Necrosis Factor (TNF): Has toxic effects on tumor cells; involved in inflammation.
          - Hematopoietic Cytokines: Control stem cell development into blood cells.

Antigens, Epitopes, and Antibodies

  • Antigens: Substances inducing antibody production, often found on pathogens, including proteins and polysaccharides.

  • Epitopes: Specific regions on antigens that antibodies bind to.

  • Antibodies: Y-shaped molecules forming antigen-antibody complexes, which lead to agglutination, opsonization, neutralization, and complement activation.

Classes of Antibodies

  • IgG: Most common, present in large amounts in the blood; has two antigen-binding sites.

  • IgM: First produced by B cells; forms pentamer with 10 binding sites when secreted.

  • IgA: Found in body secretions; protects mucosal surfaces.

  • IgD: Present on B cells; little found in circulation.

  • IgE: Found in low concentrations; involved in allergy responses and defense against parasitic infections.

B-Cells and their Role

  • B cells: Bear membrane immunoglobulins specific for antigens; activated to secrete immunoglobulins upon antigen recognition.

  • Development: Originates from fetal liver, then produced in red bone marrow.

T-Cells and their Role

  • T-Cells: Basis of cellular immunity; bear T cell receptors (TCRs), recognize peptide fragments presented by MHC molecules.

  • Activation: Differentiates into cells that destroy target cells or secrete cytokines.

  • Development: Mature in the thymus and circulate throughout lymphoid organs.

Types of T-Cells

  • T-Helper Cells (TH): Activate B cells and other immune cells via cytokines.

  • Cytotoxic T Lymphocytes: Kill infected and cancerous cells.

  • T Regulatory Cells: Prevent autoimmune responses by destroying abnormal self-recognizing cells.

  • Memory T Cells: Quick responder upon re-exposure to antigens; long-lived.

Natural Killer (NK) Cells

  • Function: Part of the innate immune system; kill virus-infected/cancerous cells.

  • Mechanism: Release perforin and granzymes, inducing apoptosis; do not require antigen recognition.

Immunity Processes: Exposure to Antigen

  1. Primary Response: Initial exposure to antigen; slow response, primarily IgM, takes days.

  2. Secondary Response: Rapid and stronger reaction due to memory cells; primarily IgG, quick protection.

Natural vs. Artificial Immunity

  • Natural Immunity: Acquired through everyday life (active via infection; passive via maternal antibodies).

  • Artificial Immunity: Obtained through medical interventions (active via vaccination; passive through antibody injection).

Chapter 20: Antibiotics and Immune Response

  • Penicillin Discovery: Found by Alexander Fleming; first antibiotic-use in treating bacterial infections, revolutionized modern medicine.

  • Sources of Antibiotics: Naturally sourced mainly from soil bacteria (e.g., Streptomyces) and certain fungi (e.g., Penicillium).

  • Bacteriostatic vs. Bactericidal:
      - Bacteriostatic: Inhibits growth but doesn’t kill; requires immune system for eradication.
      - Bactericidal: Directly kills bacteria.

Drugs Influencing Nucleic Acid Synthesis

  • Quinolones: Inhibit DNA gyrase, preventing DNA replication.

  • Rifamycins: Block RNA polymerase, halting transcription.

  • Sulfonamides: Inhibit folic acid synthesis in bacteria (human cells acquire it via diet).

Antifungal Drugs

  • Examples: Polyenes, azoles, echinocandins, and allylamines.

  • Mechanism:
        - Polyenes: Bind to ergosterol in fungal membranes.
        - Azoles/Allylamines: Inhibit ergosterol synthesis.
        - Echinocandins: Prevent fungal cell wall synthesis.

  • Effectiveness: Attention required for side effects due to shared characteristics with eukaryotic human cells.

Interferons and Antiviral Treatments

  • Function: Produced in response to viral infections, signaling neighboring cells to produce antiviral proteins.

  • Therapeutic Use: Treat viral infections and some cancers.

Influenza Treatments

  • Mechanism: Target stages of viral life cycle:
        - Neuraminidase Inhibitors: (e.g., oseltamivir) prevent virus release.
        - Entry/Inhibition Blockers: (e.g., amantadine) stop viral entry or uncoating.

Selective Eukaryotic Targeting

  • Drugs: Anti-fungal, protozoan, antihelminthic (e.g., azoles, metronidazole).

  • Challenge: Eukaryotic pathogens are similar to human cells, increasing potential side effects.

Antibiotic Resistance Behaviors

  • Contributors:
      - Not completing prescriptions.
      - Using antibiotics for viral infections.
      - Overuse in livestock and incorrect dosing.

  • Consequence: Allows resistant bacteria to survive, reproduce, and spread.