5: Cytokines and chemokines Flashcards
purpose of cytokines (3)
- regulate and mediate host immune responses via direct action on cells
- homeostatic roles
- activate or suppress immune activities
are cytokines antigen-specific in action
no (act on other host cells)
are individual cytokines made my one cell type or more than one
made by more than 1 cell type
do cytokines act on one cell type or many
many
how do cytokines interact with each other (2)
- influence synthesis of other cytokines
- influence actions of other cytokines
4 families of cytokines
- growth factors
- interleukins
- interferons
- chemokines
what are growth factors
stimulators of hematopoiesis that regulate immature leukocyte growth and differentiation –> drive terminal differentiation of hematopoietic progenitors
examples of growth factors (4)
- granulocyte-colony stimulating factor (G-CSF)
- macrophage-CSF
- oncostatin M
- interleukin-3 (IL-3)
what are interleukins
mediators and regulators of lymphocytes and leukocytes –> regulate innate and adaptive functions of immune cells
examples of interleukins (6)
- IL-2
- IL6
- IL8
- IL10
- IL12
- tumor necrosis factor-alpha (TNF-a)
what are interferons
mediators and regulators of antiviral and innate immunity –> activate intracellular processes that inhibit viral replicaton (interfere with viral replication)
examples of interferons (3)
- IFN-gamma
- IFN-alpha
- IFN-beta
what are chemokines
chemoattractants –> regulate the directed movement of immune cells from the blood into tissues
examples of chemokines (4)
- MIP-1a
- IL-8
- RANTES
- MCP-2
cytokine receptors info
- expressed on many cell types and show considerate regulation of expression
- highly specific
- receptors grouped into families
types of cytokine units
- single subunit
- multimeric (homomultimeric and heteromultimeric)
how do IFN-a/b interfere with viruses (3)
- activate host genes to inhibit viral RNAs and replication
- induce MHC class I expression on the host cells
- activate NK cells to kill virally-infected cells
functions of IFN-gamma (2)
- most potent activator of macrophage immune function
- increased microbicidal activity
what produces IFN-gamma (2)
t helper cells and NK cells
what are primary sources of IFN-a/b (3)
t cells, macrophages, fibroblasts
purpose of colony-stimulating factors (CSF)
promote the terminal differentiation of omnipotent or polypoent progenitor cells
4 types of colony-stimulating factors
- granulocyte colony-stimulating factor
- macrophage CSF
- granulocyte or macrophage (GM) CSF
- IL-7
IL-1 info
- principal regulator of the host inflammatory response
- produced by many, esp activated macrophates and epithelial cells
- 2 forms (IL-1a and IL-1b) with overlapping activities
main functions of IL-1 (3)
- CNS: fever, sleepiness
- vascular endothelia: adhesion molecule expression, IF-gamma synthesis
- hepatocytes: acute phase protein expression
IL-2 info and functions
- produced by activated TH1
- primary autocrine growth factor for t-cell proliferation
- b cell proliferation regulation
- stimulates cytotoxic t and NK cell activity
- enhances macrophage function
what produces IL-6
activated macrophages, t cells, fibroblasts, and bone marrow stromal cells
functions of IL-6
- liver: induces acute phase protein expression by hepatocytes
- hypothalamus: causes fever
IL-12 info
- influences differentiation of naive t cells toward Th1 pathway
- produced by dendritic cells and macrophages
- determines the type of immune response that predominates
tumor necrosis factor info
- principal mediator of endotoxic shock
- produced by activated macrophages and NK cells
functions of TNF-a
- hepatocytes: increased catabolism, acute phase protein expression, proliferation
- macrophages: decreased proliferation, increased phagocytosis, IL production
- tumor cells: cytolysis
- endothelial cells: IL-1 production, adhesion molecule expression
- fever
how does TNF affect vascular endothelium
activates vascular endothelium to begin process of extravasation (adhesion molecules get neutrophils out of blood to where they are needed)
endotoxic or septic shock
- overexpression of cytokines –> inflammation
- TNF-a is the major cytokine responsible
- fever, acidodis, hypotension –> multiple organ system failure –> death
IL-4 and IL-10 info
- principal regulators of the humoral immune response
- produced by Th2 cells
- activated mast cells release IL-4 from stored vesicles
- anti-inflammatory
functions of IL-4
- t cells: promotes growth of th2 cells, enhanced proliferation, production of th2 cytokines, inhibition of th1 differentiation
- macrophages: inhibits activation
functions of IL-10
- macrophages: inhibits activation
- t cells: inhibition of th1 differentiation
what cells produce chemokines
- phagocytic cells
- t cells
- endothelial cells
- fibroblasts
3 types of chemokines
- IL8: chemotactic for neutrophils
- MIP-1a: chemoattractant for CD8+ t cells and neutrophils
- RANTES: chemoattractant for memory CD4+ t cells, eosinophils, and monocytes
how do b cells and t cells communicate
using cytokines for initial activation of b cells and for b cell differentiation into plasma cells
what else do cytokines assist in
isotype switching –> adaptive immune response
inhibition of organ transplant rejection
- cyclosporin A treatment
- corticosteroids to inhibit proinflammatory cytokine production
how do steroids inhibit inflammation
inhibit NF-kB (transcription factor) activation of cytokines –> no transcription of NFkB target genes)
what is anti-TNF-alpha therapy used for
treating rheumatoid arthritis (binds TNF before it can bind to receptor)
