Cytokines Flashcards
recruitment of neutrophils is mainly mediated by what family of cytokines
CXC chemokines
Monocyte recruitment is more dependent on what family of chemokines
CC chemokines
Receptors of chemokines belong to the ______ superfamily
Seven-transmembrane, guanosine triphosphate (GTP)-binding (G) protein-coupled receptor (GPCR) superfamily
Chemokine receptors are expressed on all leukocytes, with the greatest number of diversity seen on
T cells
The main actions of chemokines are
enhancing adhesion of circulating leukocytes to endothelium through integrin activation and stimulating directed leukocyte movement in tissues by chemoattraction
What are chemokine roles in inflammation
- Increased adhesion of leukocytes in endothelium
- Migration of leukocytes to site of infection or tissue damage
CCL2 (MCP-1)
- Chemokine Receptor: CCR2
- Fxn: Mixed leukocyte recruitment (monocyte)
CCL19 (MIP-3beta)
- Chemokine receptor: CCR7
- Fxn: T cell and dendritic cell migration into parafollicular zones of lymph nodes
CCL21 (SLC)
- Chemokine receptor: CCR7
- Fxn: T cell and dendritic cell migration into parafollicular zones of lymph nodes
CXCL8 (IL-8)
- Chemokine receptor: CXCR1, CXCR-2
- Fxn: Neutrophil recruitment
CXCL10 (IP-10)
Chemokine receptor: CXCR3, CXCR3B
Fxn: Effector T cell recruitment
CXCL12 (SDF-1alphabeta)
- Chemokine receptor: CXCR4
- Fxn: Homing naive B cells to LNs
CXCL13 (BCA-1)
- Chemokine Receptor: CXCR5
- Fxn: B cell migration into follicles; T follicular helper cell migration into follicles
XCL1 (Lymphotactin)
- Chemokine Receptor: XCR1
- Fxn: T cell and NK cell recruitment
CX3CL1 (Fractalkine)
- Chemokine Receptor: CX3CR1
- Fxn: T cell, NK cell, and monocyte recruitment; CTL and NK cell activation
Cytokines of innate immunity that result in inflammation
- TNF
- IL-1
Cytokines of innate immunity that lead to resistance to viral infection
- IFN-alpha/beta
IFN-gamma functions
macrophage activation
IL-12 functions
- IFN-gamma production by NK cells and T cells
IL-15 function(s)
Proliferation of NK cells
Cytokines that control inflammation
- IL-10
- TGF-beta
IL-2
- Principal Cell Source
- T cells
- Cytokine Receptor and Subunits
- CD25 (IL-2Ralpha)
- CD122 (IL-2Rbeta)
- CD132 (Yc)
- Principal Cellular Targets and Biologic Effects
- T cells
- Proliferation and differentiation into effector and memory cells
- promotes regualory T cell development, survival, and function
- NK cells
- Proliferation and activation
- B cells
- Proliferation, antibody synthesis (in vitro)
- T cells
IL-4
- member of Type I cytokine family
- Principle cell source:
- TH2 cells
- Mast cells
- Principle function
- B cells:
- Isotype switching to IgE
- T cells
- Increases differentiation to TH2 cells
- Macrophages
- alternative activation and inhibition of IFN-gamma-mediated classical activation
- Mast cells
- Proliferation (in vitro)
- B cells:
IL-5
- Member of Type I cytokine family
- Principle cell source:
- TH2 cells
- Group 2 innate lymphoid cells
- Principle function:
- Eosinophils:
- activation
- increased generation
- B cells:
- proliferation, IgA produciton (in vitro)
- Eosinophils:
IL-17
- type I cytokine family
- Principle Cell source
- TH17 cells
- group 3 innate lymphoid cells
- Principle functions
- Endothelial cells
- Chemokine produciton
- Macrophages:
- increased chemokine and cyokine production
- Epithelial cells:
- GM-CSF and G-CSF prodution
IL-22
- Type II cytokine family
- Principle cell source:
- TH17
- Principle cellular targets and function:
- Epithelial cells:
- Production of defensins
- increased barrier function
- Hepatocytes:
- Survival
- Epithelial cells:
BAFF
- TNF superfamily cytokines
- Principal cell source
- Dendritic cells
- monocytes
- follicular dendritic cells
- B cells
- Principle cell target and function
- B cells:
- survival
- Isotype switching to IgA
- B cells:
APRIL
- TNF superfamily cytokines
- Principle cell source
- T cells
- dendritic cells
- monocytes
- follicualr dendritic cells
- Principal cell targets and function
- B cells:
- survival
- proliferation
- Isotype switching to IgA
- B cells:
TGF-beta
- IL-1 family cytokines
- principle cell source:
- T cells (mainly Tregs)
- Macrophages
- Principle cell target and functions
- T cells:
- inhibition of proliferation and effector functions
- differentiation of TH17 and Treg
- B cells:
- Inhibition of proliferation
- IgA production
- Macrophages
- inhibition of activation
- stimulation of angiogenic factors
- Fibroblasts
- increased collagen synthesis
- T cells:
IL-18
- IL-1 family cytokines
- Principle cell source
- Monocytes
- macrophages
- dendritic cells
- Kupffer cells
- Keratinocytes
- Chondrocytes
- synovial fibroblasts
- osteoblasts
- Principle targets and functions
- NK cells and T cells:
- IFN-gamma synthesis
- Monocytes
- expression of GM-CSF
- TNF
- IL-1beta
- Neutrophils:
- Activation
- cytokine release
- NK cells and T cells:
TNF
- TNF Superfamily cytokines
- Principle cell source:
- Macrophages
- NK cells
- T cells
- Principle targets and bilogogic effects
- Endothelial cells:
- activation (inflammation, coagulation)
- Neutrophils:
- Activation
- Hypothalamus
- Fever
- Muscle, fat:
- catabolism (cachexia)
- Endothelial cells:
IL-10
- Type II cytokine family member
- Principle cell source
- Macrophages
- T cells (mainly Tregs)
- Principal cell targets and functions
- Macrophages, dendritic cells
- inhibition of expression of IL-12, costimulators, and class II MHC
- Macrophages, dendritic cells
IL-22
- Type II cytokine family members
- Principle cell source:
- TH17
- principle targets and functions:
- Epithelial cells:
- production of defensins
- increased barrier function
- Hepatocytes:
- survival
- Epithelial cells:
IL-23
- Type I cytokine family
- Principle cell source
- Macrophages
- dendritic cells
- Principle targets and functions
- T cells
- differentiation and expansion of TH17 cells
- T cells
IL-12
- Type I cytokine family
- Principle cell source
- Macrophages
- Dendrites
- Principle targets and functions
- T cells
- TH1 differentiation
- IFN-gamma synthesis
- increased cytotoxic activity
- NK cells and T cells:
- IFN-gamma synthesis
- increased cytotoxic activity
- T cells
IL-7
- Type I cytokine family
- Principle cell souce
- Fibroblasts
- bone marrow stromal cells
- Principal targets and functions
- Immature lymphoid progenitors
- proliferation of early T and B cell progenitors
- T lymphocytes
- survival of naive and memory cells
- Immature lymphoid progenitors
IL-15
- Type I cytokine family
- Principle cell source
- Macrophages
- Principle target and function
- NK cells:
- proliferation
- T cells
- survival and proliferation fo memory CD8+ cells
- NK cells:
CCL25
- Receptor: CCR9
- Lymphocyte recruitment into lamina propria of intestines
- T cell-independent IgA class switching in the gut
- TLR ligand-activated DCs secrete BAFF, APRIL, and TGF-Beta which induce IgA class switching in B cells
- This T cell independent pathway yields relatively low-affinity IgA Ab to intestinal bacteria (meanwhile T dependent produces high-affinity IgA abs)
The ____ receptor binds IgA produced in the lamina propria to the base of the epithelial cells.
Poly-Ig Receptor
Are there Th17 cells in the colon
NO
Th17 produce IL-17 and IL-22 that have what effects on the GI tract
- induce expression of mucins and Beta-defensins
What are the factors that contribue to the generation of Treg cells in the GI
- Ag-activated DCs
- Local production of retinoic acid (which promotes FoxP3 expression)
- local production of TGF-beta (which also promotes FoxP3 expression and inhibits the generation of Th1 and Th2 cells)
Treg cells suppress immune responses by the production of
IL-10
Mutation in the IL-10 and IL-10R genes are associated with severe ____ in children
Colitis
Deficiencies in what cytokines or their receptors result in pathogic bowel inflammation
- TGF-beta
- IL-10
- IL-2
underlying mechanisms of the oral tolerance include
- Anergy
- Deletion
- Treg mediated suppression
What antibodies are a sensitive diagnostic marker for celiac disease
- anti-gluten IgA and IgG
- Auto-abs for Transglutaminase 2A (enzyme that modifies the gluten protien Gliadin)
People who carry the tow class II HLA alleles ____ and ___ are at high risk for development fo celiac disease
HLA-DQ2 and HLA-DQ8
IL-13
- Principal cell source
- Th2 cells
- NKT cells
- group 2 innate lymphoid cells
- mast cells
- Prinicipal functions:
- B cells:
- isotype switching to IgE
- Epithelial cells:
- Increased mucus production
- Fibroblasts:
- increased collagen synthesis
- Macrophages:
- Alternative activation
- B cells: