Infection 6: Pathogenesis of viral hepatitis

Question 1

Which types of patient would persistent HBV occur in and why?

Answer 1

Age at Infection
HbeAg only antigen that crosses the placenta
- Induces tolerance to HbcAg (most immunogenic)
- Suppress immune mediated elimination of
infected cells
- Switches immune response to Th2

Immunosuppression- Inadequate CMI
Weak/narrow intrahepatic CD4+ /CD8+ cell response
- High viral load: anergy, exhaustion of T and B cells

    -  Antiviral therapy: recovery of HBV specific CD4+/
       CD8+ cells

Question 2

Describe the role of IL10 and how it causes persistent HBV infection

Answer 2

Down regulates antiviral immune responses

  - CD4+ and CD8+ suppression with inhibition of IFN-γ and  IFN-α  production 
  - Promotes apoptosis of  plasmacytoid dendritic cells

Attenuates inflammatory response but at cost of efficient antiviral immune responses

Question 3

List 5 risk factors which affect the course of Hep B (5)

Answer 3

Age at Infection

Immunosuppression

Host immune response

HBV genotype and mutations

Coexisting risk factor: Alcohol, HCV, HIV

Question 4

Why chronicity?

Answer 4

High replicative rate and viral antigen load
- CD8+/CD4+ anergic/exhausted: unable to
proliferate/secrete cytokines
- Display normal immune responses to other
viruses

High error rate of RNA dependant RNA polymerase leading to mutations (quasispecies)
- Escape neutralizing antibodies and
cellular immune responses
HCV proteins interfere with immune response
- NS proteins inhibit innate immune responses
(recognition of TLR) through disruption of
RIG-I signalling
- Core protein down regulates IL-12 production

Neutralizing AB (core, envelope, NS3, NS4) 
    develop too slowly, too late, short lived  inducing HCV escape mutations

Question 5

Describe 2 mechanisms which cause chronic Hep C

Answer 5

High replicative rate and viral antigen load
- CD8+/CD4+ anergic/exhausted: unable to
proliferate/secrete cytokines
- Display normal immune responses to other
viruses

High error rate of RNA dependant RNA polymerase leading to mutations (quasispecies)
- Escape neutralizing antibodies and
cellular immune responses
HCV proteins interfere with immune response
- NS proteins inhibit innate immune responses
(recognition of TLR) through disruption of
RIG-I signalling
- Core protein down regulates IL-12 production

Neutralizing AB (core, envelope, NS3, NS4) 
    develop too slowly, too late, short lived  inducing HCV escape mutations