Host Defenses I: Overview and Innate Defenses

Host Defenses I: Overview and Innate Defenses

The Concept of Immunity

  • Immunity

    • The ability to ward off disease

  • Susceptibility

    • Lack of resistance to a disease

Overview of Immune Defense Mechanisms

  • BIG PICTURE: The human body constantly fights against microbial pathogens that require a host for survival.

  • Defense Levels:

    • First-Line Defenses:

    • Protect the body by keeping pathogens out or neutralizing them before infection occurs.

    • Components: Skin, mucous membranes, antimicrobial substances.

    • Second-Line Defenses:

    • Activated when first-line defenses fail; aimed to slow or contain infections.

    • Components: Proteins inducing inflammation, fever (enhances cytokine activity), phagocytes, and natural killer (NK) cells.

    • Third-Line Defenses:

    • Specific defenses targeting particular pathogens; includes a memory component for future responses.

    • Components: Lymphocytes (B cells and T cells) target specific pathogens.

Types of Immunity

  • Innate Immunity

    • General defenses against any pathogen, present from birth, and respond rapidly.

  • Adaptive Immunity

    • Immunity tailored to specific pathogens, slower to activate, and includes a memory function.

Link Between Innate and Adaptive Immunity

  • Toll-like Receptors (TLRs):

    • Receptors on host defense cells that bind to pathogen-associated molecular patterns (PAMPs).

  • PAMPs:

    • Molecular structures found commonly in pathogens, such as:

    • LPS: Outer membrane of Gram-negative bacteria

    • Peptidoglycan: Cell wall of Gram-positive bacteria

    • Flagellin: Protein in flagella

    • Nucleic Acids: DNA and RNA in viruses

  • Cytokines:

    • Small signaling proteins released due to TLR activation, governing immune responses.

    • Functions:

    • Innate: Recruit immune cells and stimulate inflammatory response.

    • Adaptive: Activate cells in adaptive immunity.

The First Line of Defense: Skin and Mucous Membranes

  • Physical Factors:

    • Skin:

    • Epidermis: Outer layer made of keratinized, tightly packed epithelial cells.

    • Dermis: Inner layer composed of connective tissue.

    • Mucous Membranes:

    • Linings that produce mucus to trap pathogens.

    • Ciliary Escalator: Mechanism that moves trapped microbes away from the lungs.

    • Lacrimal Apparatus:

    • Responsible for draining tears that wash the eye.

    • Other bodily fluids:

    • Saliva, urine, and vaginal secretions help dilute and wash away microbes.

Chemical Factors in First Line of Defense

  • Sebum:

    • Forms a protective film and lowers skin pH (3-5) to thwart microbial growth.

  • Lysozyme:

    • Found in various secretions (perspiration, tears, saliva, urine), destroys bacterial cell walls.

  • Normal Microbiota:

    • Competes with pathogens for nutrients and space, produces harmful substances, modifies local conditions to inhibit pathogen survival (Probiotics).

The Second Line of Defense: Formed Elements in Blood

  • Blood Composition:

    • Plasma: Fluid portion of blood.

    • Formed Elements:

    • Erythrocytes (red blood cells)

    • Leukocytes (white blood cells)

    • Platelets

  • Hematopoiesis:

    • The process of creating blood cell components in red bone marrow.

Types of Leukocytes

  • Granulocytes:

    • Visible granules when observed under a microscope.

    • Includes:

    • Neutrophils: Phagocytic cells active in early infections.

    • Basophils: Release histamine, mediating inflammation and allergic responses.

    • Eosinophils: Attack parasites and combat allergic reactions.

  • Agranulocytes:

    • Granules not visible under microscopic observation.

    • Includes:

    • Monocytes: Migrate to tissues and differentiate into macrophages, contributing to phagocytosis.

    • Dendritic Cells: Present in tissues; initiate the adaptive immune response.

    • Lymphocytes: B cells, T cells, and NK cells, part of adaptive immunity.

Differential White Blood Cell Count

  • Measures leukocyte concentrations and indicates health status:

    • Leukocytosis: High WBC count; often indicates bacterial infections or autoimmune conditions.

    • Leukopenia: Low WBC count; can indicate viral infections or malignancies.

The Lymphatic System

  • Components:

    • Lymph: Fluid circulating through the system.

    • Lymphatic Vessels: Transport lymph throughout the body.

    • Lymphoid Tissues: Include thymus, lymph nodes, tonsils.

    • Red Bone Marrow: Site of hematopoiesis.

Overview of Lymphatic System Functioning

  • Interstitial fluid enters lymphatic capillaries, becoming lymph and flowing through larger vessels.

  • Lymph flows through lymph nodes containing fibers that trap pathogens and immune cells.

  • Eventually, lymph enters the bloodstream and is recycled as plasma.

Phagocytes and Phagocytosis

  • Phagocytosis Mechanism:

    • Chemotaxis: Attraction of phagocytes to sites of infection via chemical signals.

    • Adherence: Attachment of phagocyte to microbe.

    • Ingestion: Engulfment of the microbe by pseudopods forming a phagosome.

    • Digestion: Phagosome combines with lysosome to digest the microbe in a phagolysosome.

    • Outcome: Undigested materials are expelled from the cell.

Inflammation

  • Definition: Localized defensive response to tissue injury.

  • Signs and Symptoms:

    • PRISH: Pain, Redness, Immobility, Swelling, Heat.

  • Functions of Inflammation:

    • Destroy harmful agents, limit their effects, and initiate tissue repair.

  • Types of Inflammation:

    • Acute: Rapid development, self-limiting; primarily involves neutrophils.

    • Chronic: Slow and severe, prolonged duration; involves monocytes and macrophages.

Phases of Inflammation

  • Immediate Response:

    • Vasodilation and increased blood vessel permeability leading to redness and heat accumulation.

  • Movement of Phagocytes:

    • Margination and diapedesis allow phagocytes to exit blood vessels to the site of infection.

  • Tissue Repair:

    • Involves regeneration of stroma and parenchyma, with outcomes ranging from perfect healing to scarring.

Fever

  • Definition: Abnormal elevation in body temperature often in response to infection.

  • Mechanism: Cytokines signal the hypothalamus to set a higher temperature increasing immune response efficiency.

  • Risks: Complications like dehydration or cardiovascular issues arise at severe elevated temperatures (over 44-46 °C).

Antimicrobial Substances

  • Complement System:

    • Over 30 proteins that enhance immune response and destroy microbes via a cascade of activation pathways.

  • Interferons (IFNs):

    • Cytokines that provide antibacterial and antiviral functions.

    • Types: IFN-α, IFN-β, and IFN-γ: each with specific responses to infections.

  • Iron-Binding Proteins:

    • Proteins such as transferrin and lactoferrin that limit free iron available for pathogens, inhibiting their growth.

Summary of Innate Immunity Defenses

  • First Line of Defense:

    • Physical and chemical barriers: Skin, mucous membranes, and normal microbiota.

  • Second Line of Defense:

    • Defensive cells (phagocytes and NK cells), inflammation, fever, and antimicrobial substances (complement, IFNs).

  • Body's Resistance Factors:

    • Genetic resistance, age, and maintaining healthy practices contribute to overall immunity.