Microbial Immune Evasion Mechanisms

Question 1

How have pathogens evolved to get past the complement system?

Answer 1

• failure to trigger- LPS, capsules
  
  • negative binding- coating with non-fixing IgA, capsule blocks C3b binding, capsule prevents C3b receptor access
  • disrupt regulation- Factor H sequestration
  • block/expel MAC- C5a proteases, blebbing

Question 2

What is the role of the complement system?

Answer 2

• induces inflammatory response
  
  • promotes chemotaxis
  • Increased phagocytosis by opsonisation
  • Increased vascular permeability
  • mast cell degranulation
  • lysis of cell membranes

Question 3

How do intracellular pathogens evade the innate immune system?

Answer 3

Phagocytosis Macrophages + PMNs
kill cell - leucocidins - Staphs
prevent opsonisation - protein A (binds Fc portion of IgG) - Staphs
block contact - capsules -meningococcus, Hib
Intracellular pathogens:
- Promote own uptake (safe) - CR3; mannose lectin receptors
- Prepares cell for invasion - Shigella
- Inhibit Phagosome-lysosome fusion - M. tuberculosis
- Escape Phagosome-lysosome to cytoplasm - Listeria
- Resist oxidative killing - produce catalases/peroxidases

Question 4

What mechanisms enable pathogen life inside of a macrophage

Answer 4

1. Directs phagocytosis via CR3 – no ROI
   
   2. Actin rearrangement - +ve engulfmant
   3. Type 3 secretion systems – prepares cell
   4. Resists digestion and ROIs in PLs - SOD, catalase
   5. Escape into cytoplasm e.g. Listeria
   6. Inhibits PL fusion maintains early endosome
      - Blocks acidification e.g. mycobacteria
   7. Controls antigen presentation
      - Stops CTLs or Pf activation

Question 5

How can pathogens evade the adaptive immunity?

Answer 5

Concealment of antigen
- hide inside cells
- privileged sites
- block MHC antigen presentation - Herpes -ve TAP protein
- surface uptake of host molecules e.g. CMV and beta2microglobulin
Immunosuppression
- e.g. Decreased MHC, decreased receptors, apoptosis, cytokine switch IgA proteases
Antigenic variation
Persistence/latency/reactivation

Question 6

What pathogenic mechanisms does streptococcus pneumoniae utilise?

Answer 6

Pathogenic mechanisms:
	- Colonisation
	- By-pass defences
	- Survival
	- Damage
Pneumonia; otitis media; meningitis

Question 7

How do different viruses evade the immune system?

Answer 7

Intracellular pathogens - requires adaptive cell mediated immunity

1. Latency  - VZV, herpes simplex
2. Decreased antigenic presentation
- by binding to TAP  - inhibits peptide transfer to MHC
- Herpes simplex
3. Decreased MCH expression      - Cytomegalovirus (CMV)
4. Mutation of epitopes 
- B cells - neutralisation escape
- T cells - CD8+ escape mutants of HIV

Question 8

How does gonorrhoeae evade the immune system?

Answer 8

Neisseria gonorrhoeae
Surface components interact with host cells
Components vary at high frequency in a population of bacteria
Variation to avoid immune response

Phase and antigenic variation in Neisseria affects cell surface components
All of these structures can undergo either:
Phase variation i.e. an ON-OFF switch (capsule, Opa’s)
Antigenic variation e.g. pilins (or both phase and antigenic)

Question 9

How can antigenic variation be used to evade the immune system?

Answer 9

Phenotype changes - colony morphology, virulence, serotype loose flagella, change surface sugars
Strategy for immune evasion and pathogenesis
Antigenic Diversity/ polymorphisms
- genetically stable and alternative forms of antigens in a population of microbes
- e.g. serotypes of Strep.pneumoniae
Antigenic Variation
- successive expression of alternative forms of an antigen in a specific clone or its progeny
- Phase variation - ON/OFF of an antigen at low frequency
- occurs - during course of infection in an individual host
- during spread of microbe through a community