22 - Immune Responses in Viral Infection

Question 1

How is viral infection prevented

Answer 1

Type 1 IFN and neutralising antibodies

Question 2

What is immune response to viruses triggered by

Answer 2

Innate immune sensing of viral nucleic aids

Question 3

TLR3

Answer 3

In endosome, binds dsRNA and signals via TRIF to induced IFN gene expression

Question 4

TLR7

Answer 4

In endosome, binds ssRNA and signals via MyD88 to induce IFN gene expression

Question 5

Viral nucleic acids activate transcription factors (IRF proteins and NFkappaB)

Answer 5

Leads to translocation into the nucleus and activation of the production of IFN alpha and beta

Question 6

Type 1 IFN

Answer 6

• Induce anti viral state
• Produced by most cell types in response to sensing by PRRs
• Plasmacytoid DCs produce high levels

Question 7

Production of IFNα/β

Answer 7

• Rapid (within hours), declines by 10h
• IFN binding to IFN receptors leads to synthesis of >1000 cell proteins (IFN stimulated genes)

Question 8

Example of IFN stimulated gene important in antiviral immunity

Answer 8

Tetherin (CD137)

Question 9

Global effects of IL-1, IL-6 and TNF alpha

Answer 9

Fever, Fatigue, Sleep

Question 10

What reflects the communication of innate and adaptive immune defense

Answer 10

• The classic inflammatory response (heat, swelling, redness, pain)
• No inflammatory response leads to ineffective adaptive response (reason for using adjuvants)

Question 11

NK cell ‘missing self’

Answer 11

• NK Cell cytotoxic functions are inhibited by self antigens presented to them by abudany MHC class 1 on the surface of cells
• When these MHC class 1 molecules are reduced, the inhibitory NK cell receptor is not engaged, triggering NK cells to release effector proteins

Question 12

ADCC

Answer 12

• Antibody binds antigens on surface of target cell
• FCγRIII (CD10) on NK cell recognise bound antibody
• Cross linking of receptor signals the NK cell to kill target cell by apoptosis

Question 13

IFN-γ antiviral effects

Answer 13

• Produced by Th1 CD4 and CD8 cells
• Inhibits viral replication directly
• Upregulates expression of MHC and components of antigen processing pathway
• Activates macrophages, recruiting them to sites of infection as both effector cells and APCS

Question 14

Generation of a primary anti viral T cell response

Answer 14

• Recognition of antigens on activated APCs by naive T cells during viral infection predominately results in the generation of Th1 cells due to the presence of type I IFNs and
  IL-12
• Th17, Th2 and TReg cells are also generated to some degree in certain viral infections

Question 15

Major mechanism for clearing viral infected cells

Answer 15

CD8 CTLs

Question 16

CD8 CTLs

Answer 16

• 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 17

CTL levels in typical cytopathic virus infection

Answer 17

• Appears within 3-5 days after infections
• Peaks about 1 week, declines thereafter

Question 18

Bystander CD8 T cells

Answer 18

• Activated by IL-12 and IL-18 made by DCs
• Produce IFN-gamma to activate macrophages (no direct killing)

Question 19

Viral evasion of MHC-1 presentation

Answer 19

• Producing abundant viral protein that is resistant to degradation by the proteasome, reducing viral epitope display (e.g. EBV)
• Encode proteins that block function of TAP, preventing transport of peptides from proteasome to ER (e.g. herpes)
• Degrade vesicles containing MHC-1 complexes
• Block MHC-1 complexes from leaving golgi body

Question 20

How does HIV evade neutralising antibodies

Answer 20

• Via glycosylation of surface glycoproteins
• Additional N-linked glycosylation sites in the viral E gene confer escape from neutralisation

Question 21

Two types of variation that allow repeated infection with Influenza virus

Answer 21

Antigenic drift and antigenic shift

Question 22

Antigenic drift

Answer 22

Emergence of point mutations with altered binding sites for neutralising antibodies on the surface HA

Question 23

Antigenic shift

Answer 23

Occurs when RNA segments are exchanged between viral strains in a secondary host (reassortment of segmented RNA genomes)

Question 24

How can antiviral antibodies enhance infection and disease instead of neutralising it

Answer 24

• FcR mediated enhancement
• Immune complexes and inflammation