Microbiology - 5 - Survival

Question 1

What is virulence and virulence factors?

Answer 1

Virulence

• ability of an organism to cause disease

Virulence factor

• bacterial product or strategy that contributes to ability to cause infection
  
  • invasion & colonization of host defenses (breach innate immunity)
  • evading complement & phagocytes
  • evading Ab response

Question 2

What are the seven different virulence factors that allow
microbes to be successful at invasion and colonization in the human host?

Answer 2

1. penetrating skin/mucin layer
   
   • biting arthropods
     
     • lyme disease
     • borrelia burgdorferi
   • entry thru wound/impant
     
     • staphylococcus aureus
2. resisting antibacterial peptides (defensins)
   
   • Defensins = form channels in bacterial membrane
     
     • gram (-) = protective
   • Pepsidases secreted to degrade defensins
     
     • porphyromonas gingivalis
3. adherence (biofilms)
   
   • sessile (surface attached) community of microorganisms
   • self-produced matrix
4. sIgA proteases
   
   • sIgA = dimerized IgA
     
     • cleavage of sIgA by bacterial proteases
     • at hinge region
   • contribute to dev of pneumonia
   • n. gonorrhae
5. iron acquisition
   
   • siderophores - compound that bind iron w/ high affinity
   • hemolysin/cytolysin - bacterial toxin that kill cell to release iron
     
     • Escherichia coli
6. invasion & intracellular residence
   
   • provokes non-phagocytic cells to engulf bacteria
     
     • listeria monocytogenes
   • intracellular bacteria = OBLIGATE intracell parasite
     
     • chlamydia trachomatis
   • Prevention of acidifiation of phagosomes
     
     • legionella pneumophila
   • Prevents phagolysome fusion
     
     • TB

Question 3

how microorganisms can avoid phagocytosis?

Answer 3

1. toxin release –>
   
   • kill phagocyte
2. opsonization prevented –>
   
   • prevents Ab attachment/phagocytosis
3. contact w. phagocyte prevented –>
   
   • capsule
4. phagolysosome fusion inhibited –>
   
   • no fusion of lysosome & phagosome
5. escape into cytoplasm –>
   
   • replicated w/in cytoplasm of phagocyte
6. resistance to killing
   
   • produces antioxidants (catalase); or scavenging free-radicals

Question 4

What are the six strategies that microbes employ to
avoid complement-mediated damage?

Answer 4

Bacteria avoid complement-mediated damage by…

• acquire or mimic complement regulators
• actively inhibit complement components
• enzymatically destroy complement
• block complement lysis

1. outer capsule or coat
   
   • prevents complement activation
2. outer surface configuration
   
   • complement receptors cannot be accessed
     
     • no fixation to C3b
3. Surface structures can be expressed
   
   • divert attachment of the lytic complex (MAC) from cell membrane
4. Membrane-bound enzymes
   
   • degrade fixed complement / shed
5. Complement inhibitors
   
   • captured onto the surface
6. Direct inhibition of C3 & C5 convertase
   
   • blocks complement activation

Question 5

What are the ways microbes conceal their antigens to evade the
adaptive immune response?

Answer 5

Principle strategies:

1. concealment of Ags
   
   • parasite hides interior of host cell
     
     • HSV
   • intracellular vacuole display of antigens
     
     • HIV
   • adenoviral production of E19
     
     • combines w/ MHC I –> prevents passage to cell surface; not recognized by cytotoxic T cells
2. Antigenic variation
   
   • express self antigens/mimicry
   • taking up host Ab (Fc receptors)
   • mutation/recombination/gene switching –> changes in Ag appearance
     
     • flu!
3. immunosuppression
   
   1. staphylococcus aureus
      
      1. gram+ / facultative aerobe
   2. super Ags
      
      1. overstimulate immune system
      2. resistant to heat, proteolysis, desiccation

Lymphocytes should be able to recognize:

• any shape (B-cell)
• AA sequence (T-cells)
  
  • only if both not identical to self

Question 6

Why are persistent infections are often described as a failure of
the host defenses?

Answer 6

• peristent infection = failure of host defences
  
  • host defenses = designed to control microbial growth & spread to elimiate microbe from body
• micro may persist:
  
  1. flagrantly defiant infectious form (HBV)
  2. low or partial infectivity
     
     • adenovirus in tonsils
  3. metabolically altered state
     
     • TB
  4. non-infectious form

Latent virus infection = classic example of persistence

• HSV = viral DNA persists for many years in sensory neurons in DRG

Question 7

how latent viral infections represent persistence and identify
the four specific reasons (examples of) of their importance?

Answer 7

Latent infections can become patent…

• medical interest

Important because:

1. Reactivated
2. Associated w/ chronic disease
   
   • HBV, AIDS
3. Associated w/ cancers
   
   • HBV, EBV, nasopharyngeal carcinoma
4. Enable infectious agent to persist in host communtiy
   
   • HSV

Question 8

discuss the two events (stages) in latent viral reactivation

Answer 8

2 events/stage in latent viral reactivation:

1. Reactivation
   
   1. resumption of viral activity in the latently infected cell
      
      1. triggers, hormones, sunlight, etc
2. Spread & Replication
   
   1. can be controlled by immune system

Immunocompromised = highest risk

• pregnancy
• old age