BIOL 2314 –Chapter 22- Innate Immunity 02

Overview

  • Course context: BIOL 2314 – Chapter 22, Module 2

    • Focus: Lymphatic System & Immunity, specifically Innate Immunity.

  • Immunity relies on leukocytes originating in red bone marrow.

    • Purpose: resist damage caused by microorganisms, toxins, and cancerous cells.

    • Two broad arms:

    • Innate (nonspecific) immunity – present at birth, no memory.

    • Adaptive (specific) immunity – characterized by specificity for antigens and immunological memory.

Antigens & Epitopes

  • Antigenic determinant (epitope) = discrete molecular site recognized by lymphocyte receptors.

  • Each antigen may possess multiple, structurally distinct epitopes → multiple lymphocyte clones can bind the same antigen.

  • Term lymphocyte–epitope specificity: one receptor clone binds only its matching epitope.

Major Components of Innate Immunity

  1. Physical Barriers (genetically endowed)

    • Skin – keratinized, desquamation removes microbes.

    • Mucous membranes – line all cavities open to exterior; cilia carry trapped microbes away.

    • Fluids that flush surfaces

      • Tears, saliva, urine, mucus.

  2. Chemical Mediators

    • Cell-surface / epithelial secretions

      • Lysozyme: present in tears, saliva, sweat, nasal secretions; hydrolyzes bacterial cell walls.

      • Acids:

      • Sebum: skin surface ( \text{pH} \approx 5 ) inhibits microbial growth.

      • Gastric acid: ( \text{pH} \approx 1–2 ) kills ingested pathogens.

      • Mucus: traps particles; contains IgA, defensins.

    • Cytokines (protein ligands for cell signaling)

      • Interferons (IFNs): produced by virus-infected cells; induce neighboring cells to synthesize antiviral proteins, reduce viral replication, activate macrophages & NK cells.

      • Interleukins (ILs): e.g., IL-2—drives T-cell proliferation; pharmacologically blocked by Cyclo­sporine to prevent graft rejection.

      • Lymphokines: cytokines released by lymphocytes.

    • Eicosanoids

      • Prostaglandins: increase pain perception.

      • Leukotrienes: prolong smooth-muscle contraction (bronchoconstriction).

    • Complement proteins

      • Group of 3030 plasma proteins; activated sequentially (complement cascade).

      • Major outcomes:

      • Membrane Attack Complex (MAC) → pore formation → target lysis.

      • Opsonization → complement fragments coat pathogens, enhancing phagocytosis.

      • Amplify inflammation (chemotaxis, histamine release).

  3. Cellular Defenses (Phagocytes & Cytotoxic Cells)

    • Neutrophils

      • Produced in red bone marrow; most abundant WBC in blood.

      • Rapidly migrate from blood → infected tissue (first responders).

      • Perform phagocytosis; die after one engulfment → accumulate as pus.

      • Release cytokines, chemotactic factors, pyrogens (fever-inducing).

    • Monocytes / Macrophages

      • Monocytes circulate, exit blood → mature into larger macrophages in tissues.

      • Most efficient phagocytes; long-lived.

      • Arrive after neutrophils; secrete chemotactic factors & pyrogens.

      • Bridge to adaptive immunity by activating T & B lymphocytes (antigen presentation).

    • Natural Killer Cells (NKCs)

      • Make up ~15%15\% of circulating lymphocytes.

      • Recognize virus-infected and tumor cells without prior sensitization.

      • Kill via membrane lysis and by enhancing opsonization.

    • Basophils

      • Formed in red bone marrow; circulate then migrate to inflamed tissues.

      • Release histamine & chemotactic factors; intensify inflammation (innate) and participate in adaptive responses.

      • Involved in asthma pathophysiology.

    • Eosinophils

      • Red-bone-marrow origin; migrate to sites of allergic reaction, parasitic infection.

      • Contribute to inflammation, asthma; participate in some adaptive responses.

    • Mast Cells

      • Non-motile; reside in connective tissues of skin, lungs, digestive & urogenital tracts.

      • Release histamine, chemotactic factors → potentiate inflammation & allergies (including asthma).

  4. Inflammatory Response

    • Triggers: trauma, burns, chemicals, pathogens.

    • Chemical mediators involved: Histamine, Complement fragments, Kinins, Eicosanoids, Cytokines, Prostaglandins, Leukotrienes, Pyrogens.

    • Vascular events:

      • ↑ Vasodilation → redness & heat.

      • ↑ Capillary permeability → plasma leak → swelling (edema) & pain.

      • Fibrinogen → Fibrin: isolates & walls-off infection.

    • Local vs. Systemic:

      • Local: classic signs – redness, heat, swelling, pain at injury site.

      • Systemic:

      • Same 4 signs + widespread effects.

      • Red bone marrow releases additional neutrophils.

      • Pyrogens circulate → fever shifts hypothalamic set-point → ↑ metabolic rate, potentiates immunity.

      • Excessive histamine → bronchospasm, mucus production, tearing.

      • Severe edema may ↓ blood volume → risk of shock/death.

Interconnections & Clinical Relevance

  • Interferon therapy employed against chronic viral infections (e.g., Hepatitis C, Herpes).

  • Cyclo­sporine: immunosuppressant that lowers IL-2, preventing transplant rejection.

  • Asthma linked to hyper-reactivity of basophils, eosinophils, and mast cells; leukotrienes are therapeutic targets.

  • Complement deficiencies → recurrent bacterial infections; MAC formation critical for Neisseria clearance.

  • Fever (via pyrogens) generally beneficial by accelerating immune reactions; however, extreme fevers can denature proteins.

  • Pus formation indicates neutrophil accumulation; macrophage clearance resolves abscess.

  • Re-exposure to allergens recruits eosinophils & mast cells, illustrating overlap between innate and adaptive arms.

Key Numbers & Equations (LaTeX format)

  • Number of complement proteins: 3030

  • NK cells proportion of lymphocytes: 15%15\%

  • Skin surface acidity: pH≈5\text{pH}\approx 5

  • Gastric acidity: pH≈1−2\text{pH}\approx 1{-}2

These notes compile every concept, cell type, mediator, mechanism, and clinical correlation discussed in the transcript, structured for efficient exam review while preserving full detail.