Cytokines Flashcards
IL-1 and TNF-alpha both activate what biologic pathway?
NF-kappaB
What are the products of the NF-kappaB pathway?
Cytokines Chemokines Adhesion molecules on vascular endothelium Nitric oxide synthase Reactive oxygen species Cyclooxygenases Phospholipase A2
What stimuli can activate the NF-kappaB pathway?
IL-1 TNF-alpha IL-17 IL-18 Bacterial products (e.g., LPS) Oxidants Activators of protein kinase C Viruses UV radiation
How do glucocorticoids suppress the pro-inflammatory effects of primary cytokines?
Promote synthesis of IkappaBalpha, which sequesters NF-kappaB in the cytoplasm, preventing translocation to the nucleus
Upregulates expression of IL-1RA, which is a competitive receptor antagonist for IL-1
Increased expression of lipocortin, which inhibits phospholipase A2
What are the three subtypes of IL-1?
IL-1alpha
IL-1beta
IL-1RA
Which form of IL-1 is biologically active as synthesized?
IL-1alpha
Which form of IL-1 requires enzymatic activation?
IL-1beta
What enzyme activates the form of IL-1 requiring enzymatic activation?
Caspase 1
What is IL-1RA?
Competitive inhibitor for IL-1
“Dummy” IL-1
IL-1alpha is produced predominantly in what cells?
Epithelial cells, including keratinocytes
IL-1beta is produced predominantly in what cells?
Monocytes, macrophages, Langerhans cells, dendritic cells
Which form of IL-1 is most important for development of a contact hypersensitivity reaction?
IL-1alpha
What is main cellular source of TNF-alpha?
Activated macrophages
What cells produce IL-18?
Keratinocytes, Langerhans cells, monocytes
What interleukin works synergistically with IL-18?
IL-12
IL-18 induces proliferation, cytotoxicity, and cytokine production by what types of cells?
Th1 cells and natural killer cells
What are two principal cellular responses to TNF?
Gene transcription of mediators of inflammation
Apoptosis
What signaling pathway triggers synthesis of chemokines?
NF-kappaB
What are the Th1 cytokines?
IL-2, IL-7, IL-12, IFN-gamma
What are the Th2 cytokines?
IL-4, IL-5, IL-9, IL-10, IL-13, IL-31
What is the function of IL-10?
Inhibits T cells and macrophages
Inhibits Th1 cell and NK cell function
Suppresses IL-1, IL-6, TNF-alpha, IL-12, IFN-gamma
Inhibits costimulation of MHC II
What cytokines are most important for the innate immune response?
IL-1 and TNF-alpha
What is the major function of IL-2?
T-cell growth factor
What cytokines mimics IL-2?
IL-7
What are functions of IL-2?
T-cell growth factor
Upregulates T cell functions
Activates NK cells, macrophages, B cells
How does IL-2 affect T cells?
Induces cell cycle from G1 to S phase
Induces Bcl-2 (anti-apoptosis)
Up-regulates IL-2 receptors on T-cells
Stimulates IFN-gamma production
How does IL-2 affect NK cells?
Promotes differentiation
How does IL-2 affect B cells?
Promotes antibody synthesis
What is the nickname for IL-12?
Lethal assassin cytokine
IL-12 favors what type of T-cell response?
Th1
What are functions of IL-12?
Stimulates IFN-gamma by NK cells, T-cells
Differentiation towards Th1 cells
Suppresses IL-4 and IgE
Enhances cytolytic functions of activated NK cells and CD8+ cytolytic T-cells
What cytokine is essential for growth and differentiation of eosinophils?
IL-5?
What cells produce IL-5?
CD4+ Th2 cells
Mast cells
What chemokine attracts eosinophils?
Eotaxin
What are functions of IL-4?
Promotes IgE production by B-cells Down-regulates IL-1, IL-6, TNF-alpha, IFN-gamma Mast cell growth factor Promotes FCERI on mast cells Th2 polarization
What is the nickname for IL-5?
Eosinophil growth factor
What is the major effect of IL-10?
Anti-inflammatory
What interleukin has similar functions as IL-4?
IL-13
How does IL-13 function differ from IL-4?
Doesn’t cause Th2 polarization
What cells produce IL-31?
Th2 cells
What cytokine causes pruritus?
IL-31
What cytokine is induced by IL-18?
IFN-gamma
What are the type I interferons?
IFN-alpha and IFN-beta
What is the type II interferon?
IFN-gamma
What are the major sources of IFN-gamma?
NK cells
CD8+ T cells
Th1 CD4+ T cells
What interleukin acts as a chemokine?
IL-8
What cytokines stimulate epidermal growth?
IL-1alpha
IL-6
IL-8
How does IL-1alpha affect epidermal growth?
Autocrine stimulating of epidermal growth
How does IL-6 affected epidermal growth? What cells produce this cytokine?
Produced by macrophages and keratinocytes
Stimulates keratinocyte proliferation
How does IL-8 affect epidermal growth and what cells produce this cytokine?
Produced by fibroblasts, lymphocytes, lymphocytes, endothelial cells, monocytes, and keratinocytes
Stimulates keratinocyte mitosis
Also recruits neutrophils and lymphocytes
