Cytokines as Messenger System Flashcards
slide 11: cytokines regulate host responses to?
infection, immune responses, inflammation, and trauma
All pro-inflammatory cytokines
IL-1, 6, 8, 11, 12, 15, 18 and TNF-alpha
Pro-inflammatory cytokines are dependent on what transcription?
NF-kB
Anti-inflammatory cytokines?
IL-10, TGF-Beta
major pro-inflammatory cytokines?
TNF, IL-1, IL-6
Blocking TNF and IL-1 have been successful in patients with?
RA, IBS, or graft vs. host disease
TNF and IL-1 reduced by what 3 strategies?
neutralizing antibodies, soluble receptors, receptor antagonist
Blocking of TNF and IL-1 has not been successful in patients with..?
sepsis
administration of TNF and IL1 will produce..?
fever, systemic inflammation, shock and death
TNF/IL-1 effects on fibroblasts
proliferation, increased collagen synthesis; leads to repair
Systemic effects of IL-1, TNF?
Fever, WBC, increase acute phase proteins, decreased appetite, increased sleep-> systemic inflammation
TNF/IL-1 effect on vascular endothelium?
increase expression of leukocyte adhesion molecules, production of IL-1 and chemokines, increase procoagulant and decreased anticoagulant activity
TNF/IL-1 effects on leukocytes?
activation, production of cytokines
TNF is primarily produced by?
macrophages (alpha) and lymphocytes (beta), neutrophils, and NK cells
Most potent inducer of TNF?
endotoxin
Primary mediator of septic shock?
TNF
TNF induces endothelial cells to produce which adhesion molecules?
ICAM 1, VCAM 1, and E-selectin
What effect does TNF have on neutrophils?
activator, mediates adherence, chemotaxis, degranulation, and the respiratory burst
2 receptors TNF binds to?
TNFR p75 (receptor I) and TNFR p55 (receptor II)
What effect does TNF have on cancerous cells?
antitumor immunity through direct cytotoxic effects (apoptosis)
IL-1 is produced by which cells?
2 main: macrophages and monocytes; neutrophils, endothelial cells, keratinocytes, and others
IL-1 upregulates expression of which adhesion molecules?
ICAM-1, VCAM-1, and E-selectin
IL-1 interacts with CNS to produce…?
fever, lethargy, sleep, and anorexia
IL-1 stimulates synthesis of..?
acute-phase proteins
IL-1 can be neutralized by?
IL-receptor antagonist (IL-1ra)
Although IL-1 shares many activities with TNF, only IL-1 can produce?
IL-2 by proliferation of CD4 T lymphocytes
IL-6 is produced by..?
mononuclear phagocytic cells
IL-6 is most important inducer of?
acute phase proteins
IL-6 shares activity with IL-1, inducing fever (pyrexia), but which is more important for induction of fever?
IL-1
IL-6 stimulates differentiation of B cells into?
mature plasma cells, producing Abs
Which cytokine has primary role in Th17 immune deviation?
IL-6
IL-8 is primarily produced by… in response to?
macrophages in response to inflammatory stimulus
IL-8 is involved in activation of?
neutrophils
IL-8 is not a chemotactic for?
monocytes, but is to neutrophils
IL-12 is derived from?
2 important: DCs, mononuclear phagocytic cells; b cells, pmns, mast cells
IL-12 controls cell-mediated immunity via activation of
Th1 cells
IL-12 stimulates production of which cytokine and what does it produce?
IFN-gamma; activates and induces proliferation, cytotoxicity, and cytokine production of NK cells
IL-12 synergies with which cytokine to stimulate IFN-gamma release?
IL-18
IL-12 is a heterodimer made of which 2 subunits?
IL-12p40 and IL-12p35
IL-15 is primarily produced by?
mononuclear phagocytic cells; additional sources: fibroblasts and epithelial cells
Similar to IL-2, IL-15 is a growth factor for?
T-cells
IL-15 is a chemotactic factor for?
T lymphocytes
IL-15 is important for survival of…?
CD8 memory T cells
IFN-gamma is primarily made by which cells?
Th1 T cells and NK cells
iFN-gamma is critical for many aspects of…?
innate and adaptive immunity
IFN-gamma is most important cytokine for cell-mediated immunity by orchestrating…?
immune response to intracellular pathogens
iFN-gamma is major activator of intracellular killing of pathogens by… stimulating..?
macrophages; phagocytosis, secretion, respiratory burst, and nitric oxide production
Which two cytokines synergize to activate macrophages and NK cells?
IL-12 and IFN-gamma
IFN-gamma stimulates expression of which adhesion molecule?
ICAM-1
IFN-gamma inhibits allergies by suppressing?
IL-4 mediated effects
IFN-gamma stimulates killing by?
NK cells and neutrophils
IFN-gamma increases expression of…? and stimulates…?
MHC I and II; antigen presentation and cytokine production by APCs
Unlike type I interferon alpha and beta; IFN-gamma has only modest…. activity?
antiviral
Major anti-inflammatory cytokines?
IL-10, TGF-beta, and IL-1 receptor antagonist
Anti-inflammatory cytokines act..?
in concert with other inhibitors to regulate human immune response
IL-10 is primarily produced by
macrophages, B cells, and Treg cells
IL-10 inhibits production of which cytokines by mononuclear phagocytes?
IL-1beta, 6, 8, 12, and TNF-alpha
IL-10 inhibits expression of what by APCs?
MHC class II and co-stimulatory molecules CD 80 and CD86
IL-10 inhibits production of which cytokines by Th1 lymphocytes?
IFN-gamma and TNF-beta
IL-10 inhibits production of which cytokines by Th2 lymphocytes?
IL-4 and IL-5
IL-10 is important for maintenance of…?
tolerance to environmental allergens
TGF-beta has what unique characteristic?
is most pleiotrophic cytokine; has both stimulatory and inhibitory effects of numerous cells
TGF-beta is mainly produced by?
macrophages and Treg cells
TGF-beta stimulates…? promoting…?
fibrosis; wound healing/scar formation
TGF-beta inhibits?
macrophages and NK cells
TGF-beta is central to differentiation of?
Th17 lymphocytes
Principal action of IL-2?
survival, proliferation, and differentiation of effector and regulatory T cells
Principal action of IL-4?
B cell switching to IgE
Principal action of IL-5
activation of eosinophils
Principal action of IFN-gamma?
activation of macrophages
Principal action of IL-17
stimulation of acute inflammation?
Principal action of TGF-B
inhibition of T cell activation; differentiation of regulatory T cells
Cellular sources of IL-2?
CD4+ and CD8 t cells
Cellular sources of IL-4?
CD4 t cells, mast cells
Cellular sources of IL-5
CD4 t cells, mast cells
Cellular sources of INF-gamma?
CD4, CD8, and NK cells
Cellular sources of IL-17?
CD4 and other cells
Cellular sources of TGF-b
CD 4 t cells; many other cell types
Transcription factor for Th1 cells?
T-bet
Transcription factor for Th2 cells?
GATA-3
Transcription factor for Th17 cells?
RORgammaT
Transcription factor for T regulatory cells?
FOXP3
Add slides 34 and 36
okay, I will
Naive T cells express low-affinity receptor?
IL-2 receptor complex
IL-2 receptor complex is made up of?
beta and gamma C chains
Once naive T cell is activated by antigen and costimulated cells produce… and express…?
produce IL-2 and express alpha chain of IL-2R forming high affinity IL-2 receptor
Binding of IL-2 to receptor initiates proliferation of…?
T cells that recognized the antigen