HOst response to viruses

Question 1

Order of Innate early resposne:

Day 1 and 2

Answer 1

rise in INFs, TNFs and IL-12

Question 2

Innater early resposne;

day 2 and 3

Answer 2

NK cell medated killin

Question 3

Innate early response

Day 5-10

Answer 3

T cell mediated killing

Question 4

What immune system branch does a lot of killing off in the early stage of viral infection

Answer 4

INNATE… adaptive comes in later

Question 5

NK activity is 20-100 X better when _____ are present

Answer 5

IFNs adn IL-12

Question 6

Parts of innate immunity

Answer 6

Innate Immunity
Recognition of pattens by PRRs
Type I INF secreation
Secreation of sobule mediators: Cytokines—IL-1, TNFα, IFNγ chemokines
Complement
NK cells for direct killing of virusese and a source of INFγ

Question 7

Parts of adaptive immunity

Answer 7

Adaptive immunity
Cytokines
Cytocotoxic T cells (granule exocytosis, Fas L-induced apoptosis)
B cells and Antibiodies (neutralization, opsonization and phagocytosis)

Question 8

REview for cell cycle.. not that important

Answer 8

1. Virus enters and binds—enters epithelial cells—causes epi cells to release INFαand β to activate NK cells
2. NK cells upreguated by INFs and IL-12 (which is released by DC cell)
3. DC take processed host cell and viral proteins and releaes IL-6 and IL-1 to CD4 TH0 cells
4. THO cells release IL-2 and INF to CDH TH1
5. CDH TH1 will induce B cell, CD4 emmory, CD8 and CTL

Question 9

used to tx chronic hep C and for tx of melanoma, hairy cell leukemia, chrnoic myelogenous leukemina, Kaposi’s sarcoma

Answer 9

INFα

Question 10

Given the importantce of INFγ in driving _____immune response, woud INFs be useful for tx of virus infecion

Answer 10

Th1

Question 11

INF___ to tx MS

Answer 11

β

Question 12

Issues with interferuons

Answer 12

-Flu like symptoms after each injection (msl aches, pains, malaise) Pt on INF have issue with thinking and conc and can reduce bood counts

Question 13

Vira products (ssDNA, ds RNA and CpG DNA)→ sensed by PRRs→ cascade of signaling through adaptors and kinases→ activate TFs → these will activate:

Answer 13

IRFs or Intrferon response factors

Question 14

Once Interferoun response activators are activated… they will

Answer 14

bind to the Interferon stimulated response element and make INFapha/beta and secreate to nearby cells

Question 15

What is the benefit of an infected cell secreating INFa/b

Answer 15

inducts and antiviral state in the nearby cells by binding to INF-a/b receptor

Question 16

Type I receptor

Answer 16

INF a/b receptor that activates the PKR path

Question 17

Protein kinase R (PKR) is induced in nearby cell by

Answer 17

IFN

Question 18

PKF binds to dsRNA, autophosphorylated to phosphorylate :

Answer 18

elF-2

Question 19

when elF is P’d it wil do what to translation

Answer 19

prevent it

Question 20

2’5 OAS is induced by

Answer 20

IFN

Question 21

like PKR it binds to and is activated by

Answer 21

dsRNA

Question 22

once activated, OAS cat syntehsis of lolgoadenylate form ATP into :

Answer 22

oligoAAAA

Question 23

oligoAAAA that was adenylated from activated OAS will activate

Answer 23

RNAase L

Question 24

RNAase L is

Answer 24

endoribonucleus

Question 25

purpose of RNAaseL

Answer 25

binds to oligoAAA and dimerizes = active whith then degrades mRNA

Question 26

whats the point of the OAS path

Answer 26

to get oligoAAAA to activate and dimerize with RNAse L to degrade mRNA = NO viral protein synthesis

Question 27

INFbeta/alpha induce

Answer 27

anti-viral state

Question 28

Antiviral state will

Answer 28

decrease viral produciton increase MHC I expression increase NK cells

Question 29

Path of anitival state

Answer 29

``` a. increaes MHC class I expression→ Increase PKR expression→ 2’5’ synthase expression → increase 2’5’ oligo A (A-A) → increase viral mRNA degredation OVERALL: decrease viral protein synthesis and increase class I MCH ```

Question 30

pyrogens to induce fever

Answer 30

TNF and IL-1b

Question 31

made by activated macros, CD4 T cells and NK cells

Answer 31

TNF

Question 32

major pro-inflammatory cytokine

Answer 32

(TNF, IL-1, IL-6)

Question 33

ILB

Answer 33

can induce fever major pro-inflammaory cytokine produced and secreated by activated macrophages

Question 34

What cytokine is produced and secreated by activated macrophages

Answer 34

IL-1B

Question 35

IL-6 is

Answer 35

pro-inflammatory cytokine

Question 36

induce death signaling

Answer 36

TNF

Question 37

Mouse story: not that important... see twice

Answer 37

Mice infected with vaccinia virus (strain to make small pox) didn’t devo fever Poxvirus recombiants lacking the IL-1β binding protein have been generated…when mice are infectd w/ these, no fever Thus viral IL-1β proteins will seqester IL-1β and ≠ it’s pyrogenic activity (need fever to fight off virus)

Question 38

NK response | 1. cytotoxic… kills targets after assessing the balance between:

Answer 38

inhibitory signals from class I and activating signals from NK activating ligands

Question 39

In “first response” to virus infection, cells upregulate

Answer 39

Type I IFNs and upregulate NK activating ligands

Question 40

``` NK sees a class I MHC _____ sees a class I MHC + NK activating ligang____ ```

Answer 40

leave it be | DEATH!

Question 41

Recap on class MHC1

Answer 41

proteasome chews up protein→ TAP brings it in, assembles MHC with it’s β2m subunit and processes protein + MHC I through ER and golgi→ to cell surface

Question 42

Whos responsible for the early 'anti-viral' host defense?

Answer 42

innate | early symptoms of viral infection happen before adaptive immune system comes into play

Question 43

key for neutralizing a virus before it enters a cell

Answer 43

B cells or antiBodies

Question 44

Infected cells will often undergo

Answer 44

apoptosis from withing and from without

Question 45

signals for apoptosis without

Answer 45

Fas, TNF=alpha, CTL, NK

Question 46

Mech of apoptosis

Answer 46

go pro-capsase 9→ capsase 9→ which takes pro-cap3 to capsase-3 == end result is activated capsase 3 and you get DNA fragmentation and death