Exam 3: Cytokines Flashcards
What are cytokines?
Small, soluble proteins used by immune cells for communication
4 different cytokine properties
- Pleiotropic
- Redundant
- Synergistic
- Antagonistic
Signaling mech for many cytokines
JAK/STAT system
Role of cytokines and chemokines
fine-tuning of an immune response as it progresses
Functions of Cytokines
Stimulation (IL-2) Inhibition (TGF-β) Differentiation (IL-12, IL4, Il-23) Cell death (TNF) Chemoattract
3 modes of action
Autocrine --> Act on cell that produces them like IL-2 (respond to its own signal) Paracrine--> Act on nearby cell (class switching, T cells activating macrophages) Endocrine--> Act on distant cells via circulation (IL-1 acts on brain)
Properties of cytokines: Pleiotropy
1 cytokine has multiple effects on multiple cell types
Ex: IL-4 induces activation, proliferation, differentiation of B cells; proliferation of T cells; proliferation of Mast cells
Properties of cytokines: Redundancy
> 1 cytokine can have same effect
Ex: IL-2, IL-4, IL-5 induce proliferation of B cells
Properties of cytokines: Synergy
2 cytokines acting together have different or amplified effect than by themselves Ex: IL-4 + IL-5 dramatically increase IgE class switching when IL-5 does not have this affect alone and IL-4 exhibit lesser class switching
Properties of cytokines: Antagonism
cytokines interfere with another’s effect
Ex: IL-4 induces TH2 but inhibits TH1 and TH17; IFN-γ induces TH1 but inhibits TH2 and TH17
What cytokine(s) released by activated macrophages induce (s) change in vascular endothelium (vasodilation) that allow more leakiness of leukocytes and allow fluid to enter lymph system? (Local effect)
IL-1, TNF-α
Local effects rely on ___ levels of cytokines
Higher
Systemic effects result from TNF-α entering ____
bloodstream
Septic shock induces by __
systemic infection
Systemic infection (Too much immune response)
edema causes decreased blood volume leading to collapse of vessels, coagulation leads to multiple organ failure
What cytokines do virally infected cells secrete?
IFN-α; IFN-β
These induce resistance to viral replication replication in all cells by increasing MHC I expression and antigen presentation in all cells and activating NK cells to kill these infected cells
TH1 or TH2?
IL-2
TH1
TH1 or TH2?
IFN-γ
TH1
TH1 or TH2?
TNF-β
TH1
TH1 or TH2?
GM-CSF
TH1
TH1 or TH2?
IL-3
TH1 and TTH2
TH1 or TH2?
IL-4
TH2
TH1 or TH2?
IL-5
TH2
TH1 or TH2?
Il-10
TH2
TH1 or TH2?
IL-13
TH2
TH1 or TH2?
Help IgE production
IgG via IL-4
TH1 or TH2?
Help IgG2a production
TH1 mostly; also TH2
TH1 or TH2?
Eosinophil and Mast Cell production
TH2
TH1 or TH2?
Delayed type hypersensitivity
TH1
TH1 or TH2?
CTL activation
TH1
What are the 5 cytokine receptor families?
- Class I (hematopoietin)
- Class 2 (interferon)
- TNF
- Immunoglobulin superfamily
- Cytokine
Which receptor families are characterized by conserved cysteines in extracellular domain?
Class 1 (hemotopoein), Class II (interferon), TNF
Match ligand to receptor family: IL-4, IL-2
Class 1
Match ligand to family: IL-5
Class 1
Match ligand to family: IL-12
Class 1
Match ligand to family: IL-21
Class 1
Match ligand to family: IL-23
Class 1
Match ligand to family: IFN- alpha, beta, gamma
Class 2
Match ligand to family: TNF- alpha, beta
TNF
Match ligand to family -1
Ig superfamily
Which families utilize JAK/STAT pathway
Class 1, Class 2, TNF
CD27L, CD30L, and CD40L are membrane bound____
costimu molecules
Structure of chemokine receptors
7 transmembrane receptors using trimeric G-proteins as signaling
3 subfamilies
- GM-CSF (common beta subunit)
- IL-6 (common gp130 subunit)
- IL-2 (common gamma subunit)
based on similar signaling pathways
IL-2 Receptor (IL-2R) expression
More subunits lead to higher affinity
just alpha: low affinity (10^-8 M)
gamma and beta subunit: intermediate affinity (10^-9 M)
alpha, gamma, and beta: high affinity (10^-11 M)
need less cytokine concentration for higher affinity receptor
IL-2R (low and high affinity)
Activated CD4 and CD8 T cells and activated B cells
Naive T cells and NK cells express which IL-2R subunits
gamma and beta
Which subunit modulates IL-2R
alpha
**Describe the JAK/STAT pathway? **
cytokine receptors interact with inactive JAK (Janus kinase); cytokine binding to receptor induces receptor subunits to dimerize and activates JAK and the receptor chains are phosphorylated (specifically tyrosines); Phosphorylated tyrosines bind to SH2 containing protein STAT (STAT is phosphorylated); STAT normally inactive in cytosol, when SH2 binds to phosphorylated tyrosine on receptor, STAT becomes target and dimerize (homo and hetero): dimerized STAT move into nucleus and act as transcription factors
ESSENTIALLY JAKS BIND TO RECEPTOR SUBUNITS TO PHOSPHORYLATE DIFFERENT STATS
IL-2 receptor interacts with JAK_ and JAK_ and activates STAT_
JAK1; JAK3; STAT5
IL-4 receptor interacts with JAK_ and JAK_ and activates STAT_
JAK1; JAK3; STAT6
IL-12 receptor interacts with JAK_ and ___ and activates STAT_
JAK2; Tyk-2; STAT4
IFN-gamma receptor interacts with JAK_ and JAK_ and activates STAT_
JAKW1; JAK2; STAT1
Even with limited # JAKS, we can activate ___
different subsets of STATs based on different cytokines
Chemokine receptors structure
7 transmembrane domain receptors signal by coupling with trimeric GTP-binding proteins–> Chemotaxis
