lesson 9

• Infection


  Growth of microbes in or on the host
• Disease


  Tissue damage or injury
• Steps to Infectious Disease

  1. Reservoir

  2. Transmission

  3. Portal of Entry
• Adherence


  Microbe binds to host cells

  
• Colonization


  Growth on/in host, after microbe has gained access to host tissues

  
• Invasion


  Ability of a pathogen to enter into host cells or tissues, spread, and cause disease

  
• Pathogenicity


  Ability to cause disease

  
• Virulence


  Relative ability to cause disease

  
• Virulence factors


  • Toxic substances produced by a pathogen that directly/indirectly enhance invasiveness and host damage by promoting infection

  
• Virulence factors may be chromosomal or on a plasmid (transferable)
• LD50


  Number of cells that kill 50% of the population
• Highly virulent strains have LD50 and LD100 that are close in magnitude

  
• Attenuation


  Decrease or loss of virulence of a pathogen
• Virulence Factors in Salmonella

  • R plasmid = resistance plasmid
  • Attachment: Type I fimbriae, capsule, and H antigen of flagella
  • Invasion: Injectisome
  • Exotoxins and Endotoxins
  • Immune Evasion: Anti-phagocytic killing proteins (O and H antigens) / complement inhibitors
  • Nutrient Acquisition: Siderophores

  
• Toxic Enzymes / Toxins

  Most bacteria/fungi damage tissues by secreting enzymes or toxins
• Endotoxins


  Toxins within bacterial cell membranes that are released only when cells are lysed

  
• Lipid A is toxic: fever (pyrogenic), diarrhea, increased HR, immune stimulation, general inflammation
• Lipid A highly conserved, but slight changes modify virulence, immune evasion, etc
• Phosphate necessary for binding human receptor (TLR4) – removal = immune evasion but also less toxicity
• Endotoxins are MUCH less toxic than exotoxins
• Exotoxins


  Extremely toxic secreted proteins that work at a distance
• AB Toxins


  2 subunits - B binds to host cell surface receptor allowing A to cross membrane and damage cell

  
• AB Toxins


  • Diphtheria, tetanus, pertussis (DTaP vaccine!), botulism, cholera, shiga toxin, shiga-like toxin, anthrax edema toxin and anthrax lethal toxin
• Diphtheria Exotoxin


  Blocks Protein Synthesis
• Vaccine is a "toxoid" – modified inactive protein
• Single missense mutation destroys function but allows immune system to recognize
• Botulinum and Tetanus Toxins

  Inhibiting Neural Function
• Shiga-Toxin / Shiga-Like Toxin


  Kills Erythrocytes

  
• Targets small intestine proximal to infection, enters bloodstream and destroys RBCs by inhibiting protein synthesis
• Cytolytic Exotoxins


  Soluble proteins that damage the host cytoplasmic membrane leading to lysis and death

  
• Superantigens


  Severe and often fatal reactions, lead to overblown and more non-specific activation of large % of immune system
• Food poisoning/intoxication


  Ingestion of foods containing preformed microbial toxins
• Food infection


  Ingestion of food containing high enough numbers of pathogens to colonize and cause disease
• Norovirus (60%), Salmonella, C. perfringens, Campylobacter account for 90% of food infections

  
• Clostridium botulinum Food Poisoning

  Gram +, obligate anaerobe, endospore former found in soil and water, produces botulinum toxin only during sporulation under anaerobic conditions
• Botulinum toxin causes botulism, can be destroyed by properly cooking food to 80C for 10 min
• Salmonellosis – Food Infection

  Gram -, found in gut of many animals, fecal contamination of food leads to infection
• Immune Evasion: Invades phagocytes, grows intracellularly, kills, and spreads
• Antibiotics usually ineffective for shortening disease
• Listeriosis


  Listeria monocytogenes – Gram +, acid-, salt-, cold-tolerant, facultative aerobe found in soil and water, grows @ 4C due to membrane lipids