Lecture 20

Question 1

Intrinsic immunity

Answer 1

Virus-derived dsRNA detected by Dicer2 - cleaved to dsRNA oligonucleotides

Dicer associates with Argonaut - Duplex unwound and 1 strand selected as guide strand - loaded into RISC

RISC associates with viral mRNA by base-pairing with guide strand - mRNA is cleaved by Argonaut and mRNA inactivated

Question 2

Pathogen associated molecular pathways

Question 3

Interferon

Answer 3

Interferon-stimulated genes (ISG) induced by interferon

IFNalpha or IFNbeta binds receptor in plasma membrane, activating RTKs that phosphorylate STAT1/STAT2 heterodimer

Dimer binds IRF9 in nucleus to form complex called ISGF3 - Binds promoters of large number of ISGs to stimulate transcription

Question 4

Evidence vaccines are effective

Answer 4

Primary and secondary response

• Vaccines cause rise in specific antibodies directed against antigen - memory retained
• Re-infection will initiate the secondary response, where the same specific antibody will be synthesized much more quickly and rapidly as antigen is identified immedately

Question 5

Vaccine derived Polio

Answer 5

• Replicates in intestine and excreted - circulating vaccine-derived Poliovirus (cVDPV)
• Passive immunisation by sewage in water supply, standard faecal oral route
• cVDPV continues to circulate when immunity is low, but can revert to pathogenic form
• 24 outbreaks in 21 countries since 2000, 760 cases

Question 6

cVDPV

Answer 6

• Polio outbreak arrested with vaccination in poor santiation
• Attenuated virus shedded into sewage by passive immunisation

Question 6

What other approaches to vaccination are there?

Answer 6

• Virus-like particles
• Recombinant vaccines
• Peptide cocktail vaccines

Question 7

Advantages of peptide cocktail vaccine

Answer 7

1. Safe (we think)
2. Wide coverage
3. Cheap

Question 8

Problems with peptide cocktail

Answer 8

1. Safety?
2. How to deliver the cocktail
3. Effectiveness

Question 9

List some antiviral drugs

Answer 9

Acyclovir - Inhibits DNA synthesis in treating HSV

Ribavirin - Treats respiratory syncytial virus

Zidovudine - Treats HIV

Tenofovir - Treats HBV infections by inhibiting RT

Saquinavir - Used in HIV treatment

Amantadine - Treats Influenza A

Question 10

Categories of drug treatment for COVID-19

Answer 10

Convalescent plasma and hyperimmune serum use natural antibodies to treat COVID-19

• Synthetic antibodies
• Direct antivirals e.g. RNA polymerase inhibitors, Protease inhibitors and viral binding blockers
• Indirect treatments