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35 Cards in this Set

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What are 4 cell types that are the primary sources of TNF?
Activated monocytes
Activated T-cells
NK cells
Mast cells
What are 5 actions of TNF?
1) Mediate acute inflammatory response to infectious microbes
2) Stimulates recruitment of neutrophils
3) Induces vascular endothelial cells to express adhesion molecules
4) Stimulates endothelial cells and macrophages to induce leukocyte chemotaxis
5) Acts on mononuclear phagocytes to stimulate IL1 secretion
What are 2 types of TNF receptors?
Type I
Type II

What happens upon binding of TNF to its receptor?
Type I--apoptosis

Type II--recruitment of TRAFs, activating transcription factors (NK-kappaB, AP-1)
What are the 4 cells that are the primary sources of IL1?
Activated monocytes
Neutrophils
Epithelial cells
Endothelial cells
What is the most potent stimulus for TNF production?
Binding of TLR4 with LPS.

What cytokine augments TNF production?
IFN-gamma
What is the most potent bacterial stimulus for IL-1 production?
LPS

What cytokine augments IL-1 production?
TNF
What actions does a low concentration of IL-1 mediate?
Local inflammation and increased endothelial expression of surface molecules that mediate leukocyte adhesion.
What actions does a high concentration of IL-1 mediate?
Fever, synthesis of acute phase reactants by the liver, neutrophil and platelet production by the bone marrow.
What is the the IL-1 receptor?
Type 1 IL-1R

What molecular events accompany its binding?
MyD88 recruitment to the TIR domain, and protein kinases (IRAK4, IRAK1, TRAF6) leading to activation of NF-kappaB
What is the main action of IL-12?
Promotes differentiation of CD4 cells into Th1 polarized CD4 cells.
What are the 2 cell types that are the primary source for IL-12?
Activated dendritic cells
Macrophages
What are the 3 primary stimuli for IL-12 production?
TLR binding
IFN-gamma (from NK cells or T-cells)
CD40/CD154 interaction on macrophages and dendritic cells
What are the 2 subunits of IL-12?
p35 subunit
p40 subunit

What does p35 bind?
What does p40 bind?
What are the molecular events that follow binding?
p35 binds beta-2 subunit of IL-12 receptor, leading to JAK2 binding to STAT4

p40 binds beta-1 subunit of IL-12 receptor, leading to Tyk2 binding to STAT4
What are the 3 actions of IL-12?
Stimulates production of IFN-gamma by NK cells and T lymphocytes.
Promotes Th1 polarization of CD4 cells.
Enhances cytotoxicity of NK cells and CD8 cells.
What are the two types of "Type I interferons"?
Interferon alpha and interferon beta.

What is the most potent stimuli for type I interferon production?
Viral nucleic acid.
What are the 2 cell types that are the primary source of IFN-alpha?
Plasmacytoid dendritic cells
Monocytes
What cell types produce interferon beta?
Many cells, including fibroblasts
What is the primary action of the Type I interferons?
Inhibit viral replication
What are 5 actions of Type I interferons?
Inhibit viral replication
Increase expression of MHC class I
Polarize Th1
Promote sequestration of lymphocytes in lymph nodes
Inhibit proliferation of many cell types
What are the 2 primary cell types that produce IL-10?
Macrophages
Tregs
What are 3 actions of IL-10?
Inhibit IL-12 production by macrophages and dendritic cells
Inhibits expression of costimulators
Inhibits costimulatory receptors
What are the 3 cell types that primarily produce IL-6?
Monocytes
Vascular endothelial cells
Fibroblasts
What 2 cytokines induce production of IL-6?
IL-1
TNF
What are 4 actions for IL-6?
Stimulates synthesis of acute phase proteins by hepatocytes
Stimulates production of neutrophils from bone marrow precursors
Stimulates growth of B lymphocytes that have differentiated into antibody producers
Growth factor for neoplastic plasma cells
What cells are the principal producers of IL-15?
mononuclear phagocytes

What induces IL-15 production?
Viral infection and LPS
What are the 2 actions of IL-15?
Survival of memory CD8 T-cells, NK cells and NK-T cells
Required for NK cell differentiation and activation
What are the 2 cells that are the primary source of IL-18?
Macrophages and dendritic cells

What enzyme is required for its prodcution?
Capase-1
What are the 2 primary actions of IL-18?
Enhance IFN-gamma production by T-lymphocytes

Promotes differentiation of IFN-gamma, leading to Th1 polarization
What 3 cytokines are dependent on capase-1?
IL1, IL18, IL23
What are 3 actions of IL-23?
Contributes to inflammation in autoimmunity
Important for resistance to Klebsiella
Promotes Th17 polarization
What are the 2 cell types that are the primary source of IL-27?
macrophages
dendritic cells
What are the 3 actions of IL-27?
Promotes Th1 polarization
Promotes IFN-gamma production by T-lymphocytes
Some role in controlling ongoing T-lymphocyte responses
What pathogenic organism are people with IRAK4 deficiency particularly prone to infection with?
Strep pneumo
What type of cell naturally produces IL-1ra?
mononuclear phagocytes

What is the clinical utility of IL-1ra?
Anakinra, useful in autoinflammatory conditions
What 2 pathogenic organisms are people with IL-12Rbeta1 mutations particularly prone to infection with?
Salmonella
atypical mycobacteria