Host-Pathogen Interactions

Pathogen Entry & Colonization - Gatecrashers & Squatters

• Portals of Entry (Gatecrashing): Microbial access points.
  • Mucous Membranes: Resp (TB), GI (Cholera), GU (UTI), Conjunctiva.
  • Skin: Parenteral route (cuts, bites).
  • Placenta: TORCH (e.g., Rubella, CMV).
  • 📌 ID₅₀: Dose for 50% infection; ↓ID₅₀ = ↑virulence.
• Adherence (Sticking On): Crucial binding to host cells.
  • Pathogen adhesins (pili, M-protein) bind host receptors.
  • Determines tissue tropism (e.g., S. mutans & teeth).
• Colonization (Squatting): Establishing foothold & multiplying.
  • Overcoming local defenses (mucus, IgA, normal flora).
    • IgA proteases (e.g., N. gonorrhoeae).
  • Biofilms: Shielded communities, ↑resistance (e.g., P. aeruginosa in CF lungs, catheters).
  • Quorum sensing: Coordinated gene expression.

⭐ Helicobacter pylori uses urease to neutralize gastric acid (↑pH), allowing it to colonize the stomach lining and cause peptic ulcers.

Pathogen Virulence & Host Damage - Tiny Terrors' Tactics

• Virulence Factors: Pathogen traits enhancing disease.

  • Adhesion: Adhesins, pili, fimbriae aid colonization.
  • Invasion: Hyaluronidase, collagenase aid tissue penetration.
  • Evasion of Host Defenses:
    • Capsules (e.g., S. pneumoniae): Antiphagocytic.
    • Antigenic variation (e.g., Influenza, N. gonorrhoeae).
    • Biofilms: Protection from drugs & immunity.
    • Intracellular survival (e.g., M. tuberculosis).
  • Toxin Production:
    • Exotoxins: Secreted proteins; potent, specific.
      • A-B toxins (Cholera, Diphtheria).
      • Membrane-disrupting (Hemolysins).
      • Superantigens (TSST-1, Toxic Shock).
    • Endotoxins: Lipopolysaccharide ($LPS$) (Gram-negative outer membrane). Released on lysis.

      ⭐ LPS (Endotoxin), a PAMP, binds TLR4, releases TNF-α, IL-1, and IL-6, leading to fever, septic shock, and DIC.

• Host Damage Mechanisms:

  • Direct Damage: Direct cell lysis, toxin effects.
  • Indirect Damage (Immunopathology): Host immune response causes injury.
    • Inflammation, cytokine release.
    • Hypersensitivity reactions.
    • Autoimmunity (molecular mimicry, Rheumatic fever).

Host Immune Response - Body's Border Patrol

• Innate Immunity (Rapid, Non-specific): First line of defense.
  • Barriers: Skin, mucous membranes (physical/chemical).
  • Cells: Phagocytes (Neutrophils, Macrophages), Natural Killer (NK) cells, Dendritic Cells (DCs).
  • Receptors: Pattern Recognition Receptors (PRRs) like Toll-like Receptors (TLRs) detect Pathogen-Associated Molecular Patterns (PAMPs).
  • Mediators: Inflammation (Pro-inflammatory cytokines: TNF-α, IL-1, IL-6), Complement system (Opsonization, Membrane Attack Complex - MAC).
• Adaptive Immunity (Specific, Memory): Tailored, potent response with memory.
  • Antigen Presentation: Antigen Presenting Cells (APCs - Macrophages, DCs, B cells) process and present antigens.
    • MHC-I: On all nucleated cells; presents endogenous antigens to CD8+ T cells.
    • MHC-II: On APCs; presents exogenous antigens to CD4+ T cells.
  • Cell-Mediated Immunity (CMI):
    • CD4+ T Helper (Th) cells: Orchestrate response. Th1 (intracellular pathogens, e.g., IFN-γ release); Th2 (parasites, allergy).
    • CD8+ Cytotoxic T Lymphocytes (CTLs): Directly kill infected host cells.
  • Humoral Immunity:
    • B-lymphocytes differentiate into Plasma cells → produce Antibodies (e.g., IgG, IgM, IgA).
    • Antibody functions: Neutralization, opsonization, complement activation.

⭐ IFN-γ, produced by Th1 cells and NK cells, is crucial for macrophage activation and control of intracellular pathogens like Mycobacterium tuberculosis.

High‑Yield Points - ⚡ Biggest Takeaways

• Adherence via adhesins (pili) to host receptors is the crucial first step.
• Invasion occurs via M cells, or zipper/trigger mechanisms; intracellular survival is key for some.
• Exotoxins are specific secreted proteins; Endotoxin (LPS) from Gram-negatives causes septic shock.
• Immune evasion mechanisms include capsules, antigenic variation, and biofilms.
• Host immunodeficiency, genetics (CCR5-HIV), and age significantly impact susceptibility.
• Type III/IV secretion systems inject effector proteins, manipulating host cells.