Evasion and Subversion of Host Defenses

Question 1

List bacterial anticomplement strategies and explain how each of these strategies evades or subverts complement-mediated clearance.

Answer 1

Blocking activation
1. Masking effects
- Capsule
- Coating with IgA
- Surface modification with sialic acid or hyaluronic acid
2. Inhibitors (factors H and I)
3. Antigenic variation

Blocking effector functions
- C3b peptidase; Effects?
- C5a peptidase; Effects?
- Inhibition of binding of MAC

Question 2

Define C5a peptidase.

Answer 2

Enzyme of group A Streptococcus that inactivates the chemotactic cleavage product of the 5th serum complement component (C5a), produced by the triggering of the complement cascade

Question 3

Explain how the capsule contributes to bacterial virulence.

Answer 3

Masks surface components the can activate complement via the alternative pathway

Question 4

Explain why capsules that consist of hyaluronic acid or sialic acid are resistant to complement activation.

Answer 4

They inhibit the inhibit complement fixation (no complement cascade)

Question 5

Reading assignment: Define factors H and I and explain how they regulate complement activation through the alternative pathway (Fig. 2)

Answer 5

• Factor H: dissociates C3bBb
• Factor I: cleaves C3b into iC3b (inactive) and further degradation products C3dg and C3c

Question 6

Reading assignment: Explain why bacteria that bind to factor H are resistant to complement-mediated clearance.

Answer 6

Because factor H is a complement regulatory protein that inhibits the formation of the MAC and the lysis of the bacterium
- Binding to factor H helps the bacterium evade complement activation and destruction by the immune system

(from Chat GPT)

Question 7

List bacterial strategies against phagocytosis and phagocytic killing and explain how each of these strategies evades or subverts phagocyte-mediated clearance.

Answer 7

1. Inhibiting phagocyte recruitment and function
   - Inhibition of complement activation
   - C5a peptidase
2. Killing phagocytes
   - Leukocidins
3. Escaping or inhibiting ingestion
   - Capsule
   - Inhibition of opsonization
4. Blocking intracellular phagocytic killing
   - Inhibition of lysosome fusion with phagosome
   - Escape into the cytoplasm by lysing phagosomes
   - Resistance to lysosomal enzymes in phagolysosome
   - Inhibition of oxidative phagocytic killing

Question 8

Define leukodidin.

Answer 8

Pore-forming exotoxin

Question 9

Explain why prevention of complement activation may inhibit the recruitment of phagocytes.

Answer 9

Prevent complement –> no opsonization/chemotaxis/inflammatory response

Question 10

Define opsonophagocytosis.

Answer 10

Engulfment by macrophages and other phagocytic cells like neutrophils of bacteria opsonized with antibodies and/or complement proteins

Question 11

Describe the mechanisms of streptococcal resistance to opsonophagocytosis and host defense mechanisms.

Answer 11

• Inhibition of complement activation
  
  • M protein and hyaluronic acid capsule in GAS
  • Sialic acid in GBS
  • Capsule in pneumococci
• Host defense:
  
  • Antibody against cell wall structures
  • Antibody-mediated activation of the complement system

Question 12

Define intracellular parasitism.

Answer 12

Parasites/pathogens that grow and reproduce inside host cells

Question 13

List bacterial strategies against the adaptive immunity and explain how each of these strategies evades or subverts a specific immune response.

Answer 13

1. Immunosuppression
2. Nonspecific activation of lymphocytes (diversion of lymphocyte function)
   - Superantigens
   - Binding to MHC II and TCRs on T cells
3. Proteolysis of antibodies
4. Antigenic variation

Question 13

Define superantigen.

Answer 13

Antigens that stimulate a nonspecific T cell response

Question 14

Compare and contrast an antigen and a superantigen in T-cell activation.

Answer 14

• Antigen: leads to targeted immune response
• Superantigen: leads to nonspecific and possibly harmful immune response

Question 15

Describe the mechanism responsible for phase variation in Escherichia coli.

Answer 15

Inversion of a DNA strand containing a promoter

Question 16

Discuss why frequent antigenic shift is regarded a virulence factor.

Answer 16

Immune system will have to start adaptive immune response over because it doesn’t recognize the new antigens right away

Question 17

Discuss the impact of frequent antigenic shift on the development of an effective vaccine.

Answer 17

If the vaccine is based on a certain antigen, an antigenic shift would render that vaccine ineffective