13 - Immune response to Viral infection

Question 1

What triggers immune response to viruses

Answer 1

Innate immune sensing of viral nucleic acids

Question 2

Where are toll like receptors expressed

Answer 2

Cell surface and on endosomal surface

Question 3

Pathways that stimulate expression of antiviral interferons in response to viral nucleic acids

Answer 3

TLR 3 and TLR 7

Question 4

Type 1 interferons

Answer 4

• Antiviral state
• Produced by most cells types in response to sensing by PRRs

Question 5

Outcomes of type 1 interferons

Answer 5

• Prevents nucleocapsid trafficking
• Blocks translation
• Prevents budding

Question 6

IFN stimulated genes (ISGs)

Answer 6

IFN binding to IFN receptors leads to synthesis of >1000 cell proteins

Question 7

Example of ISG important in antiviral immunity

Answer 7

Tetherin

Question 8

Proinflammatory cytokines

Answer 8

• Initially function locally in
  antiviral defence
• In larger quantities, enter circulation, have global effects

Question 9

What is absence of inflammatory response indicative of

Answer 9

• Ineffective adaptive response
• The classic inflammatory response reflects the communication of innate and adaptive immune defence
• Reason for using inflammation-stimulating adjuvants for
  noninfectious vaccines

Question 10

NK cell ‘missing self’

Answer 10

• NK cell cytotoxic functions are inhibited by self antigens (presented by MHC 1)
• When these MHC class 1 molecules are reduced, the inhibitory NK cell receptor is not engaged
• Triggering NK cells to release effect proteins, causing apoptosis

Question 11

NK cells mediate antibody dependent cellular cytotoxicity (ADCC)

Answer 11

• Antibody binds antigens on the surface of target cell
• FC receptors on NK cell recognise bound antibody
• Cross linking of Fc receptors signals the NK cell to kill the target cell
• Target cell dies by apoptosis

Question 12

CD8+ cytotoxic T cells are the major mechanism for clearing viral-infected cells

Answer 12

• Recognise complex of viral peptide with MHC class 1 and kills infected cells
• CTL responses are effective as they eliminate virus infected cells without damaging uninfected cells
• CTL kill infected cells via perforin and granzymes

Question 13

When does CTL activity appear

Answer 13

Within 3-5 days after infection, peaks about a week and declines after

Question 14

Which pathway do viral antigens enter

Answer 14

Class 1 pathway for MHC restricted presentation to CD8+ T cells

Question 15

Viral evasion of MHC class 1 presentation

Answer 15

• Producing abundant viral protein that is resistant to degradation by the proteasome reduces viral epitope display
• encode proteins that block the function of TAP, preventing transport of peptides from proteasome to ER
• Target vesicles containing MHC-1 epitope complexes to the lysosome, so that the complex is get degraded and never reach the plasma membrane
• Encode proteins that block MHC-1 epitope complexes from leaving the Golgi so that they never reach the plasma membrane

Question 16

Neutralising antibodies

Answer 16

Antibodies bound to viral surface proteins neutralise the virus, inhibiting either initial binding to the cell or its subsequent entry.

Question 17

How does HIV evade neutralising antibodies

Answer 17

Glycosylation of surface glycoproteins

Question 18

Two types of variation allow repeated infection with Influenza virus A

Answer 18

Antigenic drift and Antigenic shift

Question 19

Antigenic drift

Answer 19

emergence of point mutations with altered binding sites for neutralising binding sites on the surface haemagglutinin

Question 20

Antigenic shift

Answer 20

• a rare event involving reassortment of segmented RNA genomes of >1 IVA viruses (from birds or
  pigs)
• Large changes in HA = new virus not previously seen in
  humans
• Antibodies and memory T cells ineffective

Question 21

Original antigenic sin

Answer 21

A memory response triggered to a similar but not identical array of antigens can potentially be less effective than a response elicited in the absence of memory

Question 22

Example of original antigenic sin

Answer 22

people infected with H1N1 during childhood were protected later in life against infections with a related virus such as H5N1 but not
infections with more distantly related H3N2

Question 23

Pathogenic immune complexes

Answer 23

• In persistent or chronic viral infection, ineffective, non-neutralising antibodies may form immune complexes with viral antigen
• These complexes are deposited in kidney or blood vessels where they provoke inflammatory responses leading to tissue damage

Question 24

Example of antibodies enhancing disease

Answer 24

FcR mediated enhancement