L15/16 Flashcards
Which cytokine communicates between the innate and adpative immune responses?
IL 12
What cytokine do Th1 cells release to classically activate macrophages and make them more microbicidal?
IFN gamma
Which cytokine do viruses induce the production of when the infect host cells? The goal here is to make neighboring cells anti-viral.
IFN
Paracrine mechanism
What cytokines are released when macrophages interact with LPS? What is the systemic effect of these?
TNF
IL 1
IL 6
Induce fever!
What are the main 4 cytokines of innate immunity?
TNF alpha IFN gamma IL 1 IL 12 B/c from macrophages & NK
What are the main 4 cytokines of adaptive immunity?
IL 2
4
5
IFN gamma
What is a cytokine storm?
Cytokine overproduction –> sepsis
Explain the anti and pro-inflam roles of IL6.
Produced from macrophages –> inflam and fever
Goes to kidney –> acute phase reactants 9MBL & C reactive protein)–> decrease inflam
Which cytokines are VERY pro-inflam?
TNF alpha
IL 1
Which cytokines are very anti-inflam?
IL 4
10
11
13
What are the 3 cytokines most important for hematopoiesis?
C-CSF & CM-CSF, neutrophils
M-CSF, macrophages
What is the general model of cytokines signaling through their receptors to create effects?
Cytokine + receptor (w/ gamma chain) Jak phosphorylates ITAMs Recruit STAT STAT get phosphorylated & dimerize Complex acts as a TF
What is the IL 7 pathway for signaling at its receptor? What disease may arise from errors in this pathway?
IL 7 + IL7R JAK 3 @ ITAM STAT 5 dimerize TF for inflam SCID: - X linked = missing gamma subunit of receptor - Autosomal = Jak 3 mutation
What is the general structure of most cytokine receptors?
1 pass TM receptors
What is the general structure of most CHEMOKINE receptors?
7 TM GCPR
Describe the IL 1 receptor.
Ig superfamily receptors
TIR internal domain - recruits MyD88
Similar to TLR signaling via MyD88
Which cytokine is the primary mediator of the inflammatory response to gram negative infection?
TNF
Explain the signaling pathway of gram negative bacteria to get TNF release. (Hint: LPS)
LPS + TLR4
TRAM & TRIF pathway
IFN
Which cytokine mediates RA?
Increased TNF & IL1
From macrophages & fibroblasts in synovial fluid
↑COX 2 –> PGE2
↑NO, adhesion molecules, IL-6
What is a role unique to IL1 in RA?
↑osteoclast activity
What is a role unique to TNF in RA?
↑apoptosis
How do you treat RA?
TNF antagonists:
- Methotrexate
Abs against TNF = Adalimumab or Etanercept
What happens if you get rid of too much TNF?
Can’t fight infection normally
Happens with immune suppression
Latent disease (TB) can recur
What is an anti-IL 1 Ab used for? Explain the mechanism.
= IL-1ra = recomb protein
Goal = anti-inflam
We make our own version of this but half life is really short!
Prevents IL 1 binding b/c won’t let receptor dimerize with accessory protein –> no signal
Competitively inhibits the receptor
Explain the inflammasome activation in gout.
Inflammasome makes IL-1beta active
Now uric acid crystal joint to further dirve the production of IL-1beta
Use IL-1ra to treat and trap IL-1
Which cytokine can cause significant tissue damage if not controlled?
IL 12 B/c will stimulate: Th1 Macrophages NK CD8 Net = kill target cells, tissue will be bystander
What cytokines act on naive T cells to cause them to differentiate into Th17 cells?
IL 6
TGF beta
Which disease would you give IFN gamma for?
CGD
What cell type do chemo/radiation kill off first? What can you give to help this?
Neutrophils
Leaves your innate immune system weak - susceptible to infection
Give G-CSF –> increase PMNs from the bone marrow
If you give IFN beta therapy to MS patients, which cytokine’s production will be suppressed?
IL 12
Changes to IL 10 production –> leads to creation of those pro-inflam cytokines
How IFN beta could decrease inflam that causes neurologic damage in MS
