Immune response to virus infection

Question 1

what antiviral cytokines do infected cells and plasmacytoid dendritic cells produce?

Answer 1

type I interferons alphas and beta

Question 2

How do plasmacytoid dendritic cells detect viral nucleic acids?

Answer 2

TLR7 and TLR9

Question 3

How do infected cells detect viral nucleic acids?

Answer 3

RIG-I and Mda-5

Question 4

What to IFN alpha and bets do?

Answer 4

inhibit viral replication by inducing ezpression of:

dsRNA activated protein kinase (PKR)

oligoadenylate synthetase

Question 5

how does PKR work to inhibit viral replication?

Answer 5

activated by dsRNA
inactivation of eIF-2alpha (translation factor)
inhibition of protein synthesis

Question 6

How does oligoadenylate synthetase work?

Answer 6

activated by dsRNA
activates RNAse L
degradation of viral RNA

Question 7

How do IFN alpha and beta facilitate immune response to viral infection/

Answer 7

promote expression of MHC class I

produce NK cells increasing cytotoxic activity

Question 8

What are NK cells?

Answer 8

lymphocytes
granular morphology
recruited to viral infected sites
important role in early stages before CTLs

Question 9

How do NK cells recognised virally infected cells?

Answer 9

• lack specific receptors
• express germ-line encoded receptors
• stress induce expression of ligands for NK activating receptors - NKG2D receptors, UL16 binding proteins, MICA/B
• virus downregulate MHC class I expression

Question 10

What ligands are present that cause cells to be killed by NK cells?

Answer 10

NKG2D

Question 11

What happens if cell lacks MHC class I?

Answer 11

Killed by NK cells 
lose MHC class I = lose inhibitory signal

Question 12

Why is there a balance between expression of certain ligands and downregulation of MHC class I?

Answer 12

balance will determine HOW the NK cells kill the target cell

Question 13

How do the contents of NK cells induce apoptosis?

Answer 13

granzymes

perforin - pores in membranes, granzymes can enter into cell cytoplasm and induce apoptosis

Question 14

How do NK cells connect to the target cell?

Answer 14

form a lytic immunological synapse - polarise at synapse

Question 15

How to granzymes from NK cells act?

Answer 15

DNA fragmentation - capsase activated DNAse
mitochondrial dysfunction

cleave proteins
targets pro-capsase 3

Question 16

What causes dendritic cells mature?

Answer 16

Danger signal e.g. viral nucleic acid via TLR3

Question 17

Where do dendritic cells move from and to?

Answer 17

originally in periphery e.g. skin, mucosa

move to lymphoid organs - present antigens to T cells & express co-stimulatory molecules

Question 18

What is the only cell that can present antigen to naive T cells?

Answer 18

Dendritic cell

Question 19

What are the 2 types of cells that are made from clonal expansion?

Answer 19

Effector cells

Memory cells

Question 20

How do CTLs detect virally infected cells?

Answer 20

T cell receptor recognises peptides bound by MHC class I

only 1-3 complexes needed for detection

Question 21

How is MHC class I antigen presented inc ells?

Answer 21

viral antigens chopped by proteasome complex

translocated in ER

MHC class I folding

TAP association & peptide binding

loaded into MHC class I molecules

Question 22

How do CTLs kill infected cells?

Answer 22

forms immunological synapse

secretory lysosomes polarise to synapse

release perforin & granzymes

ESSENTIALLY SAME AS NK CELLS

Question 23

What cells secrete antibodies?

Answer 23

• B lymphocytes

- plasma B-cells

Question 24

What are the antiviral activities of antibodies?

Answer 24

neutralisation
opsinisation
complement activation

Question 25

How do antibodies neutralise viruses?

Answer 25

bind to proteins on virus surface - prevents receptor binding on host cells neutralise IgA antibodies in mucus - prevent virus infections

Question 26

How do antibodies opsinise viruses?

Answer 26

Fc receptor bind to Fc region of antibody-antigen complexes Phagocytosis of immunoglobulin

Question 27

How do antibodies undergo complement activation

Answer 27

recruit complement proteins complement-mediated neutralisation complement-mediated virolysis phagocytosis via complement receptors

Question 28

How do vaccines protect against pathogens?

Answer 28

viral antigens in attenuated or killed form induction of memory cells

Question 29

What are the ways viruses evade the immune system?

Answer 29

- interference with IFN alpha and beta - inhibition of NK cell recognition - inhibition of CTL recognition - inhibition of complement activation

Question 30

How do viruses inhibit the IFN alpha and beta response?

Answer 30

Lassa virus - removes the stimulus for activation, dsRNA Adenovirus - inhibits IFN transcription Vaccina - binds to IFN alpha - cannot bind to receptors

Question 31

How do viruses inhibit NK cell recognition?

Answer 31

HCMV - UL16 blocks expression of NK cell ligands - stay inside cell e.g. MICA KSHV downregulates cell surface expression of MICA and MICB

Question 32

How do viruses inhibit presentation of MHC class I?

Answer 32

If peptides do not get into ER, they cannot be loaded onto MHC class I

Question 33

How do viruses inhibit complement activation?

Answer 33

Complement control proteins are encoded by host cells to prevent damage KSHC generates own - impair complement activation & complement mediated manage to membrane KCP - inhibits complement mediate lysis of KSHV virions