5: Cytokines and Chemokines Flashcards
Cytokines
small soluble proteins that regulate and mediate host immune responses via direct action on cells
What are the 3 actions of cytokines?
- Endocrine- acts on distant cell
- Paracrine- acts on neighboring cell
- Autocrine- acts on cell that secreted the cytokine
T/F: Cytokines are antigen-specific
F
T/F: Most cytokines are pleiotropic
T
JAK-Stat phosphorylation
a signal pathway that is common for many cytokine receptors
JAK
Janus kinase
What is the suffix of kinase inhibitor drugs?
-tinib
Tyrosine phosphorylation
involved in many chronic diseases and cancers (many drugs try to inhibit this reaction)
What does Apoquel inhibit?
Janus kinase-1 function, which inhibits response to and production of cytokines
What are the two types of interferons?
- Type I: IFN-alpha/beta
- Type II: IFN-gamma
IFN-alpha/beta
involved in anti-viral activity, NK activation, and upregulating MHC class I
IFN-gamma
most potent activator of macrophage immune function
Colony-stimulating factors
promote the terminal differentiation of omnipotent or polypotent progenitor cells
Macrophage CSF
CSF in monocytes/macrophages
GM-CSF
CSF in macrophages or granulocytes
IL-7
produces by stromal cells in the bone marrow or spleen; proliferation of lymphoid progenitors
What are the 3 main proinflammatory cytokines?
IL-1, IL-6, and TNF-alpha
IL-1
regulates the host inflammatory response
What cells produce IL-1?
activated macrophages and epithelial cells
What are the two forms of IL-1?
IL-1aplha
IL-1beta
What does IL-1 do to hepatocytes?
acute phase protein expression
What does IL-1 do to vascular endothelia?
adhesion molecule expression and IFN-alpha/beta synthesis
What does IL-1 do to the central nervous system?
fever induction and sleepiness
What produces IL-2?
activated TH1
What does IL-2 do?
causes autocrine proliferation of T cells
What cells produce IL-6?
activated macrophages, T cells, fibroblasts, and stromal cells of bone marrow
What does IL-6 do?
induces acute phase protein expression by hepatocytes and causes fever
What does IL-6 do to the liver?
acute phase reactant production
What does IL-6 do to the hypothalamus?
causes fever
What does IL-6 do to B cells?
plasma cell maturation and isotype switching
What does IL-12 do?
influences differentiation of naive T cells toward Th1 pathway and activates NK cells to secrete IFN-gamma
What cells produce IL-12?
dendritic cells and macrophages
What does IL-17 do?
Activates neutrophils and is helpful against extracellular bacteria
What is the most important cytokine?
tumor necrosis factor
What is tumor necrosis factor?
the principal mediator of endotoxic shock
What cells produce tumor necrosis factor?
activated macrophages and NK cells
What does tumor necrosis factor do?
cell killing, acute phase reactant expression, elicits fever, induces cytokine cascades, and activates vascular endothelial cell adhesion molecule expression
What does TNF do to tumor cells?
cytolysis
What does TNF do to endothelial cells?
IL-1 expression and adhesion molecule expression
What does TNF do to hepatocytes?
increased catabolism, acute phase protein expression and proliferation
What does TNF do to macrophages?
decreased proliferation, terminal differentiation, increased phagocytosis, reactive oxygen products, adhesion molecule expression, IL-1 production, IL-6 production, IL-12 production and GM-CSF secretion
Cachectin
a protein that is a mediator for weight loss in chronic inflammation
What is the major cytokine responsible for septic shock?
TNF-alpha
What are the major pro-inflammatory cytokines?
IL-1, IL-6, and TNF-alpha
What are the major anti-inflammatory cytokines?
IL-4, IL-10, TGF-beta
What cells produce IL-4 and IL-10?
Th2
What does IL-4 do to T cells?
promotes growth of Th2 cells, production of Th2 cytokines, inhibition of Th1 differentiation
What do IL-4 and IL-10 do to macrophages?
inhibits activation
What does IL-10 do to T cells?
inhibition of Th1 differentiation
What does TGF-beta1 do?
inhibits secretion of TNF-alpha and drives Treg cell development
What are chemokines?
small cytokines that regulate the migration of immune cells into inflammatory loci
