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)
describe CCL19/CCL21 (chemokine)
- plays an important role in trafficking of T cells in thymus and in T cell and B cell migration to secondary lymphoid organs (receptor CCR7)
describe CCL5 (RANTES) (chemokine)
- chemotactic for T cells, eosinophils, and basophils
- plays an active role in recruiting leukocytes into inflammatory sites
- induces the proliferation and activation of certain NK cells
describe CCL2 (MCP-1) (chemokine)
- monocytic chemotactic protein-1
- chemoattractant for monocytes, T-cells, mast cells, basophils, stem cells
describe CCL3 (MIP-1a)
- macrophage inflammatory protein-1a
- chemoattractant for monocytes, T- and B-cells, NK cells, mast cells, basophils, dendritic cells, stem cells
describe IL-2 (cytokines that regulate adaptive immunity)
IL-2
- source: Th1 cells
- activity: T cell growth factor
describe IL-4 (cytokines that regulate adaptive immunity)
IL-4
- source: Th2 cells
- activity: B cell growth factor
describe IL-5 (cytokines that regulate adaptive immunity)
IL-5
- source: T cells
- activity: B cell growth and immunoglobulin synthesis
describe IL-7 (cytokines that regulate adaptive immunity)
IL-7
- source: marrow/thymic stromal cells
- activity: pre-B and pre-T cell growth factor
describe IL-9 (cytokines that regulate adaptive immunity)
IL-9
- source: T cells
- activity: activates mast cells
describe IL-10 (cytokines that regulate adaptive immunity)
IL-10
- source: Th2 cells and macrophages
- activity: inhibits Th1 and macrophage function
describe IL-12 (cytokines that regulate adaptive immunity)
IL-12
- source: B cells and macrophages
- activity: activates NK cells, Th1 proliferation
describe TNF-B (cytokines that regulate adaptive immunity)
TNF-B
- source: T cells
- activity: killing by cytotoxic CD8 cells
describe IL-1 (cytokines that regulate innate immune response)
IL-1
- source: monocytes, macrophages
- activity: systemic inflammatory efefct, including fever, acute-phase protein synthesis, T-cell activation
describe IL-6 (cytokines that regulate innate immune response)
IL-6
- source: T cells, other cells
- activity: stimulates other T cells to produce IL-2, B cells to produce immunoglobulins and stem cells
describe IFN-a and IFN-B (cytokines that regulate innate immune response)
IFN-a and IFN-B
- source: viral-infected cells
- activity: interferes with viral replication, induces MHC class I expression
describe IFN-γ (cytokines that regulate innate immune response)
IFN-γ
- source: Th1 cells
- activity: activates NK cells and macrophages, induces MHC class II expression
describe TNF-a (cytokines that facilitate the innate immune response)
TNF-a
- source: macrophages
- activity: activates endothelial cells, vascular permeability
list the proinflammatory cytokines
TNF, IL-1, IL-6, chemokines (mostly)
list the anti-inflammatory cytokines
IL-4, IL-10, IL-13, TGF-B, IL-1
list the antiviral cytokines
IFN-a, IFN-B
list the macrophages activating cytokines
IFN-γ
list the B-cell activating cytokines
IL-4, IL-5, IL-6, IL-21
list the T-cell activating cytokines
IFN-γ, IL-2, IL-4, IL-12
list the eosinophil and/or mast cell activating cytokines
IL-3, IL-4, IL-5, IL-13