Notes on Host Damage by Micro-organisms and Bacterial Pathogenesis

Host Damage by Micro-organisms

Overview of Pathogenic Microorganisms

• Pathogenic microorganisms secure nutrients from their environment.
• Bacterial pathogens survive in living hosts by obtaining nutrients via tissue damage.
• They can produce a range of diseases, from those caused by a single toxin to those arising from host responses.
• Damage can be from both the pathogen and the host's response.

Common Scheme Leading to Infection

• Access: The ability of pathogens to enter the host.
• Attachment: Bacteria must adhere to host tissues.
• Avoidance: Mechanisms to evade the immune response.
• Acquisition: Methods of obtaining nutrients from the host.

Bacterial Pathogenesis Mechanisms

• Virulence Factors: Products of pathogens enhancing their ability to cause disease.
  • Act in various ways to promote pathogenicity.

Attachment Factors

• Commonly used by bacteria include:
  • Fibronectin-binding proteins: Attach bacteria to fibronectin found in the host.
  • Fimbriae: Hair-like structures aiding in attachment to host tissues.
  • Adhesins: Surface components aiding binding to host cells.

Fibronectin-Binding Proteins

• Fibronectin is crucial for bacterial colonization.
• Examples of pathogenic bacteria using fibronectin:
  • Gram Positive:
  • Corynebacterium diphtheria: Causes Diphtheria.
  • Clostridium difficile: Leads to Colitis.
  • Mycobacterium tuberculosis: Responsible for Tuberculosis.
  • Gram Negative:
  • Escherichia coli: Associated with urinary and gastro-intestinal diseases.
  • Treponema pallidum: Causes Syphilis.

Specific Adherence Mechanism in E. coli

• E. coli binds to enterocyte microvilli:
  • Uses intimin (a surface protein) and its receptor Tir.
  • The type III secretion system injects the Tir receptor into the host.
  • This initiates changes that cause microvilli to deform, creating a pedestal to facilitate colonization.

Toxins Produced by Bacteria

• Endotoxin: Part of the Gram-negative bacteria wall (e.g., LPS), highly toxic and recognized by host immune cells leading to inflammation.
• Exotoxins: Soluble proteins released outside the bacterial cell, causing localized damage.
  • A-B Toxins: Composed of active A peptide and binding B portion, can disrupt host cell function.

Cytolysins and Their Effects

• Pore-Forming Cytolysins: Create holes in host cell membranes leading to cell lysis, inflammation, and necrosis.
• Membrane Degrading Toxins (Lecithinases): Disrupt cell membranes and provoke inflammatory responses.

Superantigens

• Work by overstimulating T cells through MHC Class II and TCR interactions, leading to extensive immune responses.