HOst response to viruses Flashcards
Order of Innate early resposne:
Day 1 and 2
rise in INFs, TNFs and IL-12
Innater early resposne;
day 2 and 3
NK cell medated killin
Innate early response
Day 5-10
T cell mediated killing
What immune system branch does a lot of killing off in the early stage of viral infection
INNATE… adaptive comes in later
NK activity is 20-100 X better when _____ are present
IFNs adn IL-12
Parts of innate immunity
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
Parts of adaptive immunity
Adaptive immunity
Cytokines
Cytocotoxic T cells (granule exocytosis, Fas L-induced apoptosis)
B cells and Antibiodies (neutralization, opsonization and phagocytosis)
REview for cell cycle.. not that important
- Virus enters and binds—enters epithelial cells—causes epi cells to release INFαand β to activate NK cells
- NK cells upreguated by INFs and IL-12 (which is released by DC cell)
- DC take processed host cell and viral proteins and releaes IL-6 and IL-1 to CD4 TH0 cells
- THO cells release IL-2 and INF to CDH TH1
- CDH TH1 will induce B cell, CD4 emmory, CD8 and CTL
used to tx chronic hep C and for tx of melanoma, hairy cell leukemia, chrnoic myelogenous leukemina, Kaposi’s sarcoma
INFα
Given the importantce of INFγ in driving _____immune response, woud INFs be useful for tx of virus infecion
Th1
INF___ to tx MS
β
Issues with interferuons
-Flu like symptoms after each injection (msl aches, pains, malaise) Pt on INF have issue with thinking and conc and can reduce bood counts
Vira products (ssDNA, ds RNA and CpG DNA)→ sensed by PRRs→ cascade of signaling through adaptors and kinases→ activate TFs → these will activate:
IRFs or Intrferon response factors
Once Interferoun response activators are activated… they will
bind to the Interferon stimulated response element and make INFapha/beta and secreate to nearby cells
What is the benefit of an infected cell secreating INFa/b
inducts and antiviral state in the nearby cells by binding to INF-a/b receptor
Type I receptor
INF a/b receptor that activates the PKR path
Protein kinase R (PKR) is induced in nearby cell by
IFN
PKF binds to dsRNA, autophosphorylated to phosphorylate :
elF-2
when elF is P’d it wil do what to translation
prevent it
2’5 OAS is induced by
IFN
like PKR it binds to and is activated by
dsRNA
once activated, OAS cat syntehsis of lolgoadenylate form ATP into :
oligoAAAA
oligoAAAA that was adenylated from activated OAS will activate
RNAase L
RNAase L is
endoribonucleus
purpose of RNAaseL
binds to oligoAAA and dimerizes = active whith then degrades mRNA
whats the point of the OAS path
to get oligoAAAA to activate and dimerize with RNAse L to degrade mRNA = NO viral protein synthesis
INFbeta/alpha induce
anti-viral state
Antiviral state will
decrease viral produciton
increase MHC I expression
increase NK cells
Path of anitival state
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
pyrogens to induce fever
TNF and IL-1b
made by activated macros, CD4 T cells and NK cells
TNF
major pro-inflammatory cytokine
(TNF, IL-1, IL-6)
ILB
can induce fever
major pro-inflammaory cytokine
produced and secreated by activated macrophages
What cytokine is produced and secreated by activated macrophages
IL-1B
IL-6 is
pro-inflammatory cytokine
induce death signaling
TNF
Mouse story: not that important… see twice
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)
NK response
1. cytotoxic… kills targets after assessing the balance between:
inhibitory signals from class I and activating signals from NK activating ligands
In “first response” to virus infection, cells upregulate
Type I IFNs and upregulate NK activating ligands
NK sees a class I MHC \_\_\_\_\_ sees a class I MHC + NK activating ligang\_\_\_\_
leave it be
DEATH!
Recap on class MHC1
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
Whos responsible for the early ‘anti-viral’ host defense?
innate
early symptoms of viral infection happen before adaptive immune system comes into play
key for neutralizing a virus before it enters a cell
B cells or antiBodies
Infected cells will often undergo
apoptosis
from withing
and from without
signals for apoptosis without
Fas, TNF=alpha, CTL, NK
Mech of apoptosis
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
