Cytotoxic T Cells and Antiviral Killing

Question 1

Define incubation period.

Answer 1

The period between exposure to an infection and the appearance of initial symptoms.

Question 2

Define prodromal period.

Answer 2

• The period between the appearance of initial symptoms and the full development of a rash or fever.
• The period following the incubation period.

Question 3

To which Baltimore group do Rhinoviruses belong?

Answer 3

Group 4.

Question 4

To which Baltimore group do Adenoviruses belong?

Answer 4

Group 1.

Question 5

List 3 pattern recognition receptors used by immune cells to recognise viral PAMPs.

Answer 5

1 - Toll-like receptors.

2 - RIG-I-like receptors.

3 - Nod-like receptors.

Question 6

What are interferons?

List the types of interferons.

Answer 6

• A large family of cytokines which interfere with viral infection.
• Type 1 (includes IF-alpha and IF-beta).
• Type 2 (includes IF-gamma).
• Type 3.

Question 7

List the cells that produce IFN-alpha.

Answer 7

1 - Plasmacytoid dendritic cells.

2 - Monocytes.

*Many cells produce IFN-beta.

Question 8

Give an example of a disease that can be treated with IFN-alpha.

Answer 8

Hepatitis B / C.

Question 9

Give an example of a treatment that can be treated with IFN-beta.

Answer 9

Multiple sclerosis.

Question 10

List the cells that produce IFN-gamma.

Answer 10

1 - NK cells.

2 - T cells.

Question 11

Which molecule activates IF-gamma?

Answer 11

IL-12.

Question 12

What is the function of IF-gamma?

Answer 12

It is involved in Th1-driven immunity.

Question 13

What is the function of type 3 interferons?

Answer 13

They play a role in antifungal and antiviral immunity.

Question 14

Why are interferon-stimulated genes (ISGs) highly expressed during infection?

Answer 14

• Viral infection triggers the type 1 interferon system via immune cells.
• Interferons stimulate the expression of interferon-stimulated genes.

Question 15

What is the general function of interferon-stimulated genes?

Answer 15

They have numerous antiviral effector functions, interfering with all steps in a virus life cycle.

Question 16

List the stages of the viral life cycle.

Answer 16

1 - Entry.

2 - Uncoating.

3 - Transcription.

4 - Translation.

5 - Assembly.

6 - Exit.

Question 17

List 3 examples of interferon-stimulated genes.

Answer 17

1 - MX1.

2 - PKR.

3 - OAS1.

Question 18

List 4 specific functions of interferon-stimulated genes.

Answer 18

1 - Degradation of viral RNA through activation of RNAse.

2 - Inhibition of viral gene expression and virion assembly.

3 - Upregulation of MHC-1.

4 - Increases p53 activity, promoting apoptosis.

Question 19

How does protein kinase R (PKR) interfere with the viral life cycle?

Answer 19

• Interferons activate protein kinase R.
• Protein kinase R activates p68 kinase.
• p68 kinase phosphorylates eIF2-alpha, inactivating it.
• eIF2-alpha is required for viral translation.

Question 20

How do thiazolides work as antivirals?

Answer 20

By acting like interferons to reduce viral translation by activating protein kinase R.

Question 21

Give an example of a viral mechanism that has evolved to turn off the interferon cascade.

Answer 21

Influenza A inhibits the RIG-I-like receptor, preventing viral recognition.

Question 22

List 2 risks of dysregulation of interferon production.

Answer 22

1 - Autoinflammatory diseases.

2 - Autoimmune diseases.

Question 23

What is STING?

Answer 23

• Stimulator of interferon genes.

- Has a key role in stimulating interferon production.

Question 24

List 2 molecules that are necessary to activate STING.

Answer 24

1 - cGAS.

2 - cGAMP.

Question 25

Give an example of a disease associated with STING.

Answer 25

STING-associated vasculopathy with onset in infancy (SAVI), where STING is activated all the time.

Question 26

Which MHC class is important in viral recognition? Which cells recognise this class?

Answer 26

- MHC class I. | - CD8+ T cells.

Question 27

# Define cross-presentation. What is the consequence of cross-presentation?

Answer 27

- The ability of certain antigen-presenting cells to take up, process and present extracellular antigens with MHC class I molecules to CD8+ T cells. - The consequence is that endogenous antigens can prime CD4+ T cells, and exogenous antigens can prime CD8+ T cells.

Question 28

What is the effect of MHC class I activation?

Answer 28

Proliferation and activation of the peptide-specific CD8+ T cell.

Question 29

Give an example of a viral mechanism that has evolved to interfere with MHC class I signalling. How, in this case, are these virally infected cells destroyed?

Answer 29

- Some viruses can downregulate MHC class I expression. - In cells without MHC class I, there is no way of cells to present self proteins. - This enables NK cells to destroy the cell with downregulated MHC class I expression by recognition of non-self.

Question 30

List two methods by which NK cells cause cell death.

Answer 30

1 - By activating apoptotic receptors. 2 - By releasing their cytotoxic granules.

Question 31

List 2 roles of antibodies in the adaptive immune response to viruses.

Answer 31

1 - Neutralising antibodies, which directly kill the virus. 2 - Indirect killing by antibody-dependent cell cytotoxicity (ADCC) using non-neutralising antibodies.

Question 32

List 4 mechanisms of action of directly neutralising antibodies.

Answer 32

1 - Blocking the virus-receptor interaction that allows entry into the cell. 2 - Blocking the process of endocytosis and phagosome formation. 3 - Blocking release of the virus from the phagosome into the cytoplasm. 4 - Aggregating the virus.

Question 33

List 2 ways by which indirect killing occurs by antibody-dependent cell cytotoxicity (ADCC).

Answer 33

Antibodies bound to a virus can: 1 - Induce the classic complement cascade. 2 - Bind to Fc-gamma RIII receptors (CD16 receptors) on NK cells, which activates the NK cells.

Question 34

How might antibody-dependent cell cytotoxicity (ADCC) cause antibody-dependent enhancement of infection (ADEI)?

Answer 34

- Some viruses have no easy route into the cell. - On secondary infection, specific antibodies have been produced to the virus. - Viruses bound to the antigen binding site of the antibody can gain access to a cell if the antibody binds to the Fc receptor site on the cell.

Question 35

Give an example of a virus which gains access to cells via antibody-dependent enhancement of infection (ADEI). Which Fc receptor does this virus use as its entry receptor?

Answer 35

- Dengue virus. | - The viruses uses the Fc-gamma RIII (CD16) receptor as its entry receptor.

Question 36

Why are viruses that use antibody-dependent enhancement of infection (ADEI) worse upon reexposure?

Answer 36

Because upon reexposure, the body has produced non-neutralising antibodies which can facilitate virus uptake into cells via antibody-dependent enhancement of infection.

Question 37

What is Dengue haemorrhagic fever?

Answer 37

The syndrome caused by re-exposure to Dengue virus.