Immune Response to Viruses

Question 1

what kind of response is required for viral infections

Answer 1

cytotoxic - NK and CD8 T cells

Question 2

what is the order of response to viruses

Answer 2

1. IFN-y
2. NK cells
3. antibodies (if secondary infection)
4. CD8 T cells

Question 3

plasmacytoid dendritic cells (pDCs)

Answer 3

cells that release type I IFN (IFN-a) in response to virus binding to intracellular TLRs

Question 4

what TLRs do pDCs use

Answer 4

TLR-7 and TLR-9

Question 5

where are pDCs located

Answer 5

circulate in blood and lymphoid tissues

NOT in the tissues

Question 6

type 1 IFN

Answer 6

binds IFN-a receptors on the surface of most cells to inhibit viral replication

causes cells to produce interferon stimulated genes (ISGs) to induce an antiviral state within the cell

Question 7

antiviral state

Answer 7

shuts down protein synthesis in virally infected cells

inhibits virus from producing proteins necessary for replication

Question 8

NK cells

Answer 8

cytotoxic ILCs

release IFN-y and have cytotoxic effects in response to type I IFN

• no TCR
• present in the tissues
• release perforin and granzyme to induce apoptosis

Question 9

what receptors do NK cells express

Answer 9

1. IFN-a receptors
2. Fc receptors
3. activating and inhibitory receptors
   - bind to ligands on host cells - both activating and inhibiting to signal everything is ok
   - damaged/infected cells over-express activating receptors or under express inhibitory receptors –> gets sensed by NK cells –> kills the damaged host cell

Question 10

MHC I

Answer 10

inhibitory ligand expressed on normal host cells

normal cells express NK activating ligands and MHC I (activating and inhibitory)

viruses try to avoid detection by CD8 cells so will down regulate MHC I –> NK cells find these and kills them

Question 11

antibody dependent cell cytotoxicity

Answer 11

NK cells express Fc receptors which bind antibody coating the surface of target cells –> antibodies cross link Fc receptors –> NK cells kill target cell by apoptosis

can ONLY occur in a secondary infection

Question 12

IgM

Answer 12

located in the tissues

used against bacteria
- activates complement

Question 13

IgG

Answer 13

located in serum

used against viruses
- neutralization and ADCC

Question 14

IgA

Answer 14

located in serum and mucosal surfaces

used on mucosal surfaces
- neutralization

Question 15

IgE

Answer 15

located on mast cells

used against helminths/allergens

Question 16

how does the adaptive immune system respond to viruses

Answer 16

1. immature DCs sample antigen in peripheral tissues
2. migrate to LNs and undergo cross priming
3. present antigen to naive T cells
4. cytotoxic CD8 T cells proliferate and differentiate

Question 17

what is the role of CD4 T cells during CD8 T cell differentiation

Answer 17

release IL-2 to generate CD8 T cells

Question 18

do effector CD8 T cells require costimulation once inside the tissues

Answer 18

no

Question 19

effector CD8 T cells

Answer 19

recognize and bind infected cells –> programs target for death by releasing perforin and granzymes –> cell dies by apoptosis

Question 20

perforin

Answer 20

makes a hole in target cell membrane and injects toxic molecules

Question 21

granzymes

Answer 21

toxic molecules that activate apoptosis once inside the cytoplasm

Question 22

cross priming

Answer 22

dendritic cell takes up antigen from outside the cell but presents it as if it was from inside the cell (MHC I) in order to generate a cytotoxic CD8 T cell