Cytokines Flashcards
describe cytokines
- cytokines: low molecular weight proteins (MW <30 kDa) that regulate the immune response
- over 200
- secreted by a broad group of cells, but mainly by TH cells, dedritic cells and macrophages
- carefully regulates (no constitutive)
- act mostly locally
define interleukins, lymphokines, monokines, colony stimulating factor and chemokines
- interleukins (ILs): group of cytokines secreted by leukocytes that act on leukocytes
- lymphokines: produced mainly by lymphocytes
- monokines: produced mainly by monocytes
- colony stimulating factor: support growth of cells on semi-solid media
- chemokines: cytokines that mediate chemotaxis
describe the mechanism of action of cytokines
- bind to specific membrane receptors
- high affinity; work at low concentrations (picomolar)
- trigger signal transduction leading to gene expression
- modulate immune response; stimulate/inhibit activation, proliferation, differentiation of immune cells
name the 5 cytokine receptor families
(chemokine receptor family not shown)
describe IL-2R (cytokine receptors: class I)
- IL-2R is the most thoroughly studied cytokine receptor
- expressed by T cells for proliferation
- also called CD25, surface marker in mature T cells
- complete receptor has 3 subunits–subunits together have higher affinity for IL-2
- expressed by T cells for proliferation
describe signalling via class I and class II cytokines
- initiated by cytokine binding
- activates JAK (Janus kinase)
- phosphorylation of tyrosine
- binding of STAT (signal transducers and activators of transcription)
- translocation of STAT to cell’s DNA
- transcription of specific target genes
describe homeostatic vs. inflammatory chemokines
- homeostatic: constitutively produced in thymus and lymphoid tissue and are responsible for basal leukocyte migration
- inflammatory: these are formed under pathological conditions
- stimualted by IL-1, TNF-a, LPS or viruses
- actively participate in the inflammatory response attracting immune cells to the site of inflammation
- examples: CXCL8, CCL2 (MCP-1), CCL3 (MIP-1a), CCL5 (RANTES)
summarize the cytokines found in innate and adaptive immunity
describe the hematopoietic cytokines
describe the lineage of cells from a hematopoietic stem cell and the ILs involved
contrast the function of Th1 vs Th2 cytokines
-
Th1 cytokines activate macrophages, NK cells, and cell mediated immunity, plus the secretion of IgG isotypes
- IgG production/complement fixation
- macrophage activation
- delayed type hypersensitivity (cell-mediated)
- cytotoxic T-lymphocyte production
-
Th2 cytokines tend to favor isotype switching in the humoral immune response
- IgE production
- eosinophils
describe teh Th1/Th2 balance
- in a given immune response, either a Th1 or a Th2 response may dominate
- T helper cell cytokines of one response tend to down-regulate the other type of response
- example: Th1 cells secrete IFN-γ, which inhibits expansion of the Th2 subset
- balance of two subset determines response to disease
- example: leprosy
- tuberculoid (Th1, CMI response, good prognosis)
- lepromatous (Th2, humoral response, bad prognosis)
- example: leprosy
summarize the Th1/Th2 balance
describe the role of cytokiens in disease
- septic shock:
- bacterial endotoxin (LPS) binding to TLRs
- overproduction of IL-1 and TNF-a
- toxic shock:
- bacterial superantigens non-specifically activate T cells
- overproduction of IL-1 and TNF-a
- rheumatoid arthritis
- TNF-a
- lymphoid and myeloid cancers
- high levels of IL-6
describe the timeline of cytokine production
describe CXCL-8 (IL-8) (chemokine)
- chemoattractant for neutrophils (CXCR1, CXCR2)