4 host defense

Question 1

what is the parts of the innate immune system?

Answer 1

Innate Immunity

Recognition of patterns by PRRs Type I IFN secretion
Secretion of other soluble mediators: Cytokines – IL-1, TNFα,

IFNγ, chemokines, etc… Complement

NK cells
– direct killing of virus-infected cells by NK cells

– and, NK cells are a huge source of IFNγ pro

Question 2

what is responsible fo the early antiviral host defense?

Answer 2

the innate immune response.

Question 3

what cant you used INF gamma to treat a viral infection?

Answer 3

it is used in certain leukemias but it is limited by its side effects?

Question 4

what kind of immune response does INF gamma cause?

Answer 4

it causes a Th1 immune response

too much causes flu like sympotoms

Question 5

IFN-γ acEvates

Answer 5

macrophages.

acEvated macrophages, DC produce IL-12, TNF, IL1β

IL-12 does good things for NK cells, T cells

Question 6

what cytokine is the actiovator for NK cells?

what secretes this?

Answer 6

IL-12 is the activator for cytokines.

it is from dendritic cells.

Question 7

what aare the cytokines in the type 1 interferon response?

Answer 7

IFN -alpha

IFN - beta

Question 8

what causes the release of the type 1 interferons?

Answer 8

the PRR recognize stuff that the cell does not have like dsRNA and it causes a IRF interferon response factor that binds to the ISRE

this makes IFN alpha and beta and causes them to be released.

they go out and bind to nearby cells causing them to go in to an antivirla state.

Question 9

what is the reaction when the IFN alpha and beta bind to the receptor on others?

Answer 9

it makes the jak stat and this binds to DNA and causes them to make PKR and OAS

protein kinase R

oligoadenylate synthase.

Question 10

what is PKr?

what is it activated by?

what does it do? by blocking what?

Answer 10

it is protein Kinase R

it binds to dsRNA and phosphorylates eIF-2alpha

eIF-2 alpha

delivers Met tRNA to the 40S ribosome to initiate polypeptide synthesis

PKR stops translation.

Question 11

what is OAS?

what is it activated by?

what does it do once activated?

Answer 11

Type I IFNs activate PKR and 2’-5’ Oligoadenylate Synthase

OAS, like PKR, binds to and is activated by dsRNA

OAS makes oligo AAAA

oligo AAAA activates RNAse L – an endoribonuclease.

RNAse L degrades mRNA

OAS degrades mRNA

Question 12

IFN-α and IFN-β induce ?

what happens to viral protein sythesis?

what happens to surface MHC I

what happens to NK cells?

Answer 12

causes the antiviral state.

decrease of viral protein sythesis

increase surface class 1 MHC

increase NKcells.

Question 13

what are the proinflammatory cytokines?

what ones can induce fever?

Answer 13

major pro-inflammatory cytokine (TNF, IL-1, IL-6)

• Induces death signaling

pyrogen TNF, IL-1

Question 14

what cytokine promotes the NK production of IFN gamma?

Answer 14

IL12

Question 15

how do NK cells decide to kill a cell?

Answer 15

NK cells kill targets after assessing the balance between”

• inhibitory signals from class I molecules”
• activating signals from NK activating ligands”

Question 16

In a “first response” to virus infection, cells upregulate Type I IFNs Cells also upregulate NK activating ligands in response to virus infection

Question 17

p53 tells the cell to die or to survive?

what does it do?

Answer 17

it tells the cells to die

it makes bak pores that let out the cytochrome C

this activates caspase which goes into dna and breaks it up.

Question 18

what does bcl-2 and bcl-XL do?

Answer 18

they stop the programmed cell death from happening.

Question 19

Viruses encode proteins to prevent IFN binding!

Answer 19

Question 20

viruses can stop the IFN signalling from within.

Answer 20

bind to PKR and inactivate it.

stop the activation of the PKR

stop eif2a from binding to PKR and activating it.

Question 21

what PRR does influenza impair?

Answer 21

RIG-I

that senses the dsRNA fragments.

Question 22

the viral IL-1β binding protein serves to sequester IL-1β and stop its ___________ activity

Answer 22

its pyrogenic activity

Question 23

what are “control” proteins?

Answer 23

they are proteins that cells make to stop the complemnt proteins from binding to the cell surface and activating.

Question 24

what do viruses do to get around the complemet proteins?

Answer 24

they make homologs of the control proteins that prevent the assembly of the MAC complex.

Question 25

viruses can also stop the presentation of class I antigen presentation and diffrent steps along the wya.

Answer 25

Question 26

to evade NK cell killing, viruses can: ?

Answer 26

make some decoy MHC-1

reomove the importnet parts fo the MHC-1

stop NK cell receptors from activating on the cell surface.

Question 27

viruses can alos downregulate other adhesion molecules.

Answer 27

• adhesion molecules (ICAM-1)

costimulatory molecutes like B7

Question 28

viruses alos encode many inhibitors ofr apoptosis.

Answer 28

p53 inhibitors

vbcl-2 that inhibit them

v-caspase inhbitors

Question 29

epitope mutation is a strategy that makes more sense for viruses with _________ genomes?

b/c why?

Answer 29

with small genomes b/c they can mutate alot faster.

Question 30

The set-point of the immune/inflammatory response determines__________?

b/c why?

Answer 30

too little host defense – virus takes over
too much inflammatory response – severe disease

Question 31

2. Viruses are telling us a tremendous amount about the circuitry of the inflammatory/immune system, and pointing the way to new modulators of the system that will have applications for the treatment of disease, e.g. chronic inflammation, autoimmunity, and potential drug targets