Video 1 - Innate Immunity & Lymphatic System – Detailed Study Notes

Overview & Study Scope

• Presenter stresses the extreme complexity of the immune system and that modern science still understands only the “tip of the iceberg.”
• Goal of lecture: focus on the most important concepts so students have a working model of how innate (non-specific) defenses function before adding the adaptive layer.

Pathogens the Immune System Must Confront

• Viruses
  • Merely packets of genetic material (DNA or RNA).
  • Lack metabolic pathways; by strict definitions they are “not alive.”
• Bacteria / Prokaryotes – single-celled organisms with independent metabolism.
• Protozoa – e.g., blood-borne trypanosomes shown in slide (worm-like, undulating membrane).
• Parasites – can be microscopic or macroscopic worms.
• Abnormal self-cells
  • Result from faulty mitosis or malignant transformation.
  • Must be recognized and destroyed even though they are “self.”

Two Grand Categories of Defense

• Non-specific (Innate) Defenses
  • Present in every healthy individual from birth.
  • React the same way to almost any foreign or damaged entity.
• Specific (Adaptive) Defenses
  • Highly tailored responses (antibodies, memory B & T cells).
  • Reflect the individual’s life history of antigen exposure.

Leukocytes (White Blood Cells)

• Umbrella term for all immune cells.
• Take part in both innate and adaptive branches.

Lymphatic System Anatomy

• Lymphatic vessels (green in diagram) run parallel to the venous system, extending from the head to the toes.
• Cisterna chyli
  • Large sac-like reservoir in the mid-abdomen.
  • Collects lymph from lower limbs & gut, especially lipid-rich chyle.
• Thoracic duct
  • Continuation of cisterna chyli.
  • Empties into the left subclavian vein.
• Right lymphatic duct empties lymph from right upper quadrant into the right subclavian vein.
• Lymph nodes – bead-like swellings along vessels; high density of immune cells.
• Major lymphoid organs/tissues
  • Spleen (filters blood & removes aged RBCs).
  • Thymus (T-cell maturation; most active in childhood).
  • Bone marrow (hematopoiesis; B-cell maturation).
  • Tonsils (5 total: 1 adenoid, 2 palatine, 2 lingual).

Lymph: Definition & Contents

• Formed from the 15\% of interstitial fluid not re-absorbed by capillaries (capillaries reabsorb 85\%).
• Carries:
  • Excess tissue fluid.
  • Cellular debris / damaged cells.
  • Pathogens intentionally “invited” so they can be intercepted at lymph nodes.
  • Large dietary fats (too big for blood capillaries), especially from intestinal lacteals.

Lymph Node Micro-Architecture

• Afferent vessels > Efferent vessels → slight pressure rise, slows flow for inspection.
• Internal reticular connective tissue mesh is studded with immune cells:
  • B cells (mature in Bone marrow).
  • T cells (mature in Thymus).
  • Macrophages (phagocytes roaming within stroma).
• Clinical correlate: swollen, tender nodes indicate clonal expansion of lymphocytes reacting to antigen.

Core Functions of the Lymphatic / Immune System

• Produce, house, and deploy lymphocytes.
• Drain excess interstitial fluid and return it to blood, preventing edema.
• Filter lymph & blood, removing \approx 99\% of impurities before fluid re-enters circulation.

Innate (Non-Specific) Defenses – Three Tiers

1. First-Line Barriers

• Skin
  • Physical keratinized wall.
  • Acidic sweat & sebum (low pH) + antimicrobial proteins (e.g., lysozyme, defensins).
• Mucous membranes
  • Mucin-rich mucus traps microbes.
  • Ciliated epithelium sweeps debris toward exterior.
  • Secretions (saliva, tears) mechanically flush surfaces.
• Acidic environments
  • Gastric HCl \text{pH}\approx1.5–3.5 destroys swallowed pathogens.
  • Over-use of proton-pump inhibitors (Prilosec, Prevacid) can weaken this defense.

2. Second-Line Internal Defenses

Phagocytic Cells

• Neutrophils (60–70 % of innate phagocytes)
  • Rapid responders; generate toxic “killing zones.”
• Monocytes / Macrophages
  • In blood = monocyte; in tissues = macrophage (amoeboid).
  • Perform chemotaxis → engulf → fuse phagosome with lysosome → digest.

Lysosomal / Cytotoxic Cells

• Eosinophils
  • Concentrated in mucosa; attack large parasites by exocytosing digestive enzymes onto surface.
• Natural Killer (NK) Cells
  • Patrol for virus-infected or cancerous self cells.
  • Release perforins → punch pores → deliver granzymes → trigger apoptosis.

Inflammatory Mediators

• Basophils & Mast Cells
  • Release histamine (vasodilation → redness, warmth, edema) and heparin (anticoagulant).

Antimicrobial Proteins

• Lysozyme in tears & saliva.
• Complement (discussed further in later lectures) – plasma proteins that form MAC pores.

3. Fever (Systemic Response)

• Trigger: Phagocytes secrete pyrogens after ingesting bacteria.
• Effect: Hypothalamus raises set-point temperature.
• Physiological sequence:
  1. Chill / shiver phase – muscle contractions raise heat.
  2. Set-point plateau – iron & zinc sequestered (starves microbes); metabolism accelerates tissue repair.
  3. “Fever breaks” – set-point resets ↓, sweating dissipates heat.
• Benefits: Inhibits pathogen replication & speeds recovery unless temp becomes dangerously high.

Chemotaxis Explained

• Taxis = directional movement; Chemo-taxis = movement toward chemical gradients.
• Damaged/infected tissues release attractant molecules → guide neutrophils & macrophages to battle site.

Pathogen Evasion Strategies (Arms Race)

• Capsules or surface molecules that block phagocyte attachment.
• Resistance to lysosomal enzymes.
• Antigenic variation (e.g., Neisseria gonorrhoeae constantly alters surface proteins).

Septic Shock (Clinical Danger of Run-Away Innate Response)

• Bloodstream infection (sepsis) → cytokine storm & widespread vasodilation.
• Massive drop in blood pressure, multi-organ failure, high mortality if untreated.

Quick Comparison: Innate vs. Adaptive

Transition to Part 2

• Subsequent lecture will delve into B-cell & T-cell biology, clonal selection, antibodies, and the diverse catalog of pathogens they target.