Lec 18 - Adaptive immune responses to viral infection

Question 1

Describe the steps involved in the transition from innate to adaptive immunity.

Answer 1

1. Immature DC migrates to site via cytokines and infected cells
2. DC matures by Nf-kb activation and migrates to lymph node
3. Cytokines and MHC-2-epitopes activate naive T cells to CD4+ T cells
4. CD4+ T cells activate CD8+ T cells

Question 2

How do viruses evade exogenous antigen presentation by APCs?

Answer 2

• Reduce transcription of MHC-2
• Degrade MHC-2 in ER
• Target MHC-2 for lysosomal degradation
• Block epitopes reaching MHC-2

Question 3

What are the 2 functions of antibodies?

Answer 3

1. Neutralising = antibodies bind virion to prevent it binding receptor
2. Opsonising = APCs bind constant region of neutralising antibodies for phagocytosis

Question 4

Describe how secretory/polymeric IgA works and what type of virus they act against.

Answer 4

• Dimeric form found at mucosal surfaces
• Bind viruses inside cells if they encounter them in the same compartments for transcytosis
• Enveloped viruses

Question 5

How do viruses evade neutralising antibodies?

Answer 5

Move between cells horizontally with little time in extracellular space to reduce possible contact with antibodies

Question 6

Describe the 4 mechanisms of viral spread.

Answer 6

1. Release of assembled virions into extracellular space
2. Syncytia formation as direct cell-to-cell spread
3. Intercellular extensions with F-actin connecting distant cells
4. Intercellular pores connecting adjacent cells

Question 7

How does glycosylation effect immunity?

Answer 7

Glycan shield interferes with antibody binding

Question 8

How do viruses evade CD8+ T cell CTL function?

Answer 8

• Produce more protein resistant to proteasome degradation
• Block TAP to prevent transport of peptides from proteasome to ER
• Target MHC-1-epitope complexes for lysosomal degradation
• Prevent MHC-1-epitope complexes leaving Golgi body

Question 9

What are the 3 functions of macrophages?

Answer 9

1. Phagocytosis of antibody bound cells
2. Phagocytosis of antibody bound viruses
3. Secretion of pro-inflammatory molecules

Question 10

How does influenza and HSV-1 and smallpox evade the complement system? What is the main aim of evasion?

Answer 10

• Aim = MAC formation
• Influenza = M1 matrix protein prevents 1st complement step
• HSV-1 and smallpox = viral proteins interfere with 3rd step

Question 11

What is the role of IL-10 and how does herpesvirus utilise it to evade immunity?

Answer 11

Suppresses immune cell activity
Herpesvirus stimulates IL-10 production or encodes homologs

Question 12

How does Epstein Barr virus evade immunity during latent infection? What cell is latency established in?Describe using EBNA-1 and LMP-2.

Answer 12

• B cells
• EBV nuclear antigen 1 (EBNA-1) binds viral DNA to maintain genome as circular DNA episome
• EDV latent membrane protein 2 (LMP-2) blocks tyrosine kinase phosphorylation to prevent apoptosis in infected cells

Question 13

What are the 3 functions of anti-influenza A antibodies?

Answer 13

1. Bind HA = neutralise and opsonise for phagocytosis
2. Bind NA = inhibit degradation of sialic acid of mucus to keep virus trapped
3. Bind spike proteins on infected cells for MAC formation

Question 14

Describe the mechanism behind viral rashes and poxes. What 2 cytokines and their function as the main cause of the rash/pox seen?

Answer 14

• Mucosal primary infection
• Escape local defences and disseminate
• Th1 CD4+ T cells and macrophages home to secondary sites and produce aggressive cytokine response
• IL-2 and IFN-y = increased permeability = delayed type hypersensitivity