Immunity: History, Innate Defense, and Ion Transport Mechanisms

Concept of Immunity

• Immunity = state of being “immunis” (Latin: exempt) from disease-causing agents (pathogens).
  • Pathogens include: bacteria, archaea, protozoa, parasites, viruses.
• Two broad branches:
  • Innate / Non-specific: always “on,” targets ANY intruder (e.g., skin, mucus, pH, sneezing, generic leukocytes).
  • Acquired / Specific (Adaptive): tailored to a PARTICULAR pathogen; basis of vaccination.

Historical Milestones

• 430–404 BC Peloponnesian War
  • Only survivors of “plague” (unsure if Yersinia\ pestis) could nurse the sick → first recorded observation of acquired immunity.
• 1790s – Edward Jenner
  • Milkmaids exposed to cowpox (mild) were resistant to smallpox (severe).
  • Coined the precedent for “vaccine” (from Latin vacca = cow).
• 1878 – Louis Pasteur & Fowl Cholera
  1. Grew virulent cholera culture → injected chickens → 100 % death.
  2. Culture left on bench, became attenuated (= weakened).
  3. Injected new group → survived; mild illness only.
  4. Later challenged BOTH naïve and previously exposed chickens with fresh virulent culture:
  • Naïve chickens died.
  • Previously exposed chickens lived → demonstrated protective immunity.
    • Pasteur honored Jenner by naming the preparation a “vaccine.”
• 1881 – Anthrax Vaccine
  • Heat-attenuated Bacillus\ anthracis → vaccinated sheep → survived later virulent challenge.
• 1885 – Rabies Post-Exposure Vaccination
  • Boy bitten by rabid dog received attenuated rabies injections within \approx 2 week incubation window → survived; rare example where vaccine works post-exposure.

Innate (Non-Specific) Immunity

• Physical/chemical barriers:
  • Dead keratinized skin cells ("body armor").
  • Low pH zones (skin, stomach) inhibit microbes.
  • Reflexes: sneezing, coughing.
  • Secretions: tears (lysozyme), saliva, mucus.
• Cellular components (mentioned): generic white blood cells (e.g., neutrophils, macrophages—not detailed in transcript).

Mucociliary Escalator Example (Respiratory Innate Defense)

• Airway anatomy: trachea → bronchi → lungs; lumen = open airway space.
• Epithelium: pseudostratified ciliated epithelial cells + goblet cells.
• Mucus layer
  • Traps dust, debris, pathogens.
  • Must be sufficiently fluid so cilia beat upward (superiorly) to move the mucus to oropharynx → swallowed/digested or expectorated.

Ion & Water Movement Creating Fluid Mucus

• Key membrane proteins in an epithelial cell:
  1. NKCC co-transporter (apical): moves Na^+, K^+, Cl^- into cell simultaneously.
  • Stoichiometry often 1\ Na^+ : 1\ K^+ : 2\ Cl^- (concept, not explicitly stated).
  1. CFTR (Cystic Fibrosis Transmembrane Conductance Regulator): chloride channel on lumen side; exports Cl^- into mucus.
  2. Na^+/K^+ ATPase (basolateral): pumps 3\ Na^+ out, 2\ K^+ in → maintains gradient, prevents depolarization.
  3. K^+ leak channels: allow K^+ efflux.
• Sequence:
  1. Cl^- accumulates in cell via NKCC → exits through CFTR into lumen.
  2. Negative lumen attracts Na^+ through paracellular pathway (between cells).
  3. High [Na^+] + [Cl^-] in lumen ↑ osmolarity → water follows osmotically via same paracellular route.
  • Osmosis principle: water moves toward higher solute concentration \big( \Delta\Psi_{water} < 0 \big).
  1. Result: thin, mobile mucus propelled by cilia (“mucociliary escalator”).

CFTR Dysfunction & Cystic Fibrosis (CF)

• CF = loss-of-function mutations in CFTR channel.
  • Cl^- ╳→ lumen → no electrical pull for Na^+.
  • Absent Na^+ + Cl^- → no osmotic draw → minimal water in mucus.
  • Outcome: thick, sticky mucus that cilia cannot move → stagnation, chronic lung infections.
• CFTR also present in other organs (intestine, pancreas, sweat glands), explaining multi-system disease in CF patients.

Cholera Toxin & Intestinal CFTR

• Vibrio cholerae secretes toxins that hyper-activate CFTR in intestinal epithelial cells.
  • Excess Cl^- pumped into gut lumen.
  • Na^+ + massive water efflux (same osmotic principle) → profuse watery diarrhea (dysentery).
  • Demonstrates the flip-side: too much CFTR activity causes life-threatening fluid loss.

Acquired (Adaptive) Immunity Reference Points

• Vaccination uses attenuated (weakened) or otherwise modified pathogens to prime immune memory without causing lethal disease.
• Early live-attenuated successes (Jenner, Pasteur) laid groundwork for today’s inactivated, subunit, mRNA, and vector-based vaccines.
• Adaptive arm is pathogen-specific, long-lasting, and can be boosted.

Connections, Implications & Key Terms

• Innate and adaptive systems are complementary: innate buys time & provides broad defense, adaptive yields targeted, durable immunity.
• Ethical/Practical notes:
  • Historical experimentation (Jenner with milkmaids, Pasteur with animals & a human child) preceded modern informed-consent standards.
  • Vaccination remains a critical public-health tool, saving millions of lives annually.
• Vocabulary:
  • Pathogen – agent causing disease.
  • Attenuated – weakened form of pathogen, reduced virulence.
  • Vaccine – preparation (often attenuated/inactivated) that elicits protective immunity.
  • CFTR – chloride channel defective in cystic fibrosis; target of cholera toxin in gut.
  • Mucociliary escalator – airway defense mechanism moving mucus upward.
  • Innate vs. Adaptive – non-specific immediate response vs. specific learned response.
• Numerical / biological reference points:
  • Rabies incubation \approx 14 days → window for post-exposure vaccination.
  • Ion transport stoichiometry: NKCC:1\ Na^+ :1\ K^+ :2\ Cl^-; Na^+/K^+-ATPase: 3\ Na^+ out / 2\ K^+ in per ATP.