10 Cytokines Flashcards
what are cytokines
Secreted proteins that regulate the amplitude and duration of immune and inflammatory responses
where and how are cytokines usually produced
Usually produced transiently and locally
what are cytokines like
Extremely potent
what do cytokines bind to
Bind to specific cell-surface receptors
effect of cytokine
Change cell behaviour (signal into cell and cause change)
what are the normal levels of cytokine used for
health
what are the increasing levels of cytokine used for
At increasing levels important for disease conditions e.g. toxic shock, sepsis and organ failure
why are cytokines so important
They regulate all the important biological processes
Cytokine action
Cytokine receptors made of at least two chains, cytoplasmic domains of which bind JAKs Cytokine binding dimerizes receptor, bringing together cytoplasmic JAKs, activate each other and phosphorylate receptor Transcription factors (STATs) binds to phosphorylated receptors, in turn phosphorylated by activated JAKs Phosphorylated STATs form dimers that move into nucleus to initiate gene transcription
GF
growth factors
CSF
colony stimulating factors
Cytokine families
Hematopoietin family
TNF family
Interferon family
Chemokine family
Hematopoietins cytokine family
Small proteins, interact with its own dimeric receptor, only when all together does it signal to cell that it’s found e.g. IL-4
class 1 cytokine receptor (hematopoietin-receptor family) - IL-3, IL-5 and GM-CSF
share a common beta receptor chain and the alpha chain is different in each case
class 1 cytokine receptor (hematopoietin-receptor family) - IL-2, IL-4. IL-7. IL-9 and IL-15
have a common gamma chain, beta chain differs for each receptor. IL-2 has a third chain, high-affinity subunit IL-2R alpha (CD25)
class 1 cytokine receptor (hematopoietin-receptor family)
just have alpha or beta receptors for erythropoietin, growth hormone and IL-13
IL-2 actions
Essential role in promoting T cell division and release of mediators
Also potentiates B cell growth
Activation of NK and monocytes so is important in amplifying immune response
IL-2 production
It is produced by Th cells
TNF cytokine family
TNF-alpha
TNF-beta
how do TNF cytokine family naturally occur
Ribbon representation of TNF family cytokines - they occur naturally as trimers (TOP)
what is the monomeric TNF bound to
Monomeric TNF bound to one subunit of TNF receptor (BOTTOM)
what group of receptors are TNF receptor in
Tnf receptors are members of large group of G protein coupled receptors
Cell activation by TNF
TNF trimer binds to TNF receptor when it comes together it has a conformational change turn signalling on inside the cell
Can go down multiple routes and turn on different routes in the cell
Can lead to lead to gene activation and apoptosis
Actions of TNF
- activates macrophages, help with defense against intracellular pathogens
- induces adhesion molecules on endothelial
- Promthromobitc actions means can help cause blood clotting
- growth factor for many cells
- can also cause production of other cytokines to be produced
- Importantly regulates haematopoiesis
Interferon cytokine family
Interferon-alpha
Interferon-beta
Interferon - gamma
IL-10
Cell activation by IFN-alpha
IFN receptor is a 2-chain receptor and when ifn binds it activates Jak and Tyk
Won’t go to nucleus until activated, will bind to a specific set of genes
What is turned on = what cell will be
what makes IFN-gamma
Made by T and NK cells
Actions of IFN-gamma
Many cells increased MHC class 1/class 2
Macrophage, granulocyte and endothelial cell activation
Promotes B cell differentiation, inhibits proliferation
T cell activation
Increase NK activity
negative action of IFN-gamma
Inhibits haemopoiesis, anti-proliferative and antiviral
which IFN is most potent
IFN-gamma is less potent at antiviral and antiproliferative activities than INF-alpha and beta
Chemokine and chemokine receptor family
7 transmembrane spanning domains – cytokine receptors
Chemokine Groups
Grouped into different sets
IL-8
chemoattractant for neutrophils - migrate to site of damage
where are CXC – CXCL13 (BLC) made
stromal cells
what are the CXC – CXCL13 (BLC) receptors
CXCR5 receptors
what do CXC – CXCL13 (BLC) attract
attract B cells
CXC – CXCL13 (BLC) effect
lymphocyte homing
where are CC – CCL3 made
produced by macrophages, T cells, mast cells, fibroblasts
CC – CCL3 receptors
CCR1,3,5
what do CC – CCL3 attract
monocytes
NK and T cells
basophils
dendritic cells
CC – CCL3 effects
competes with HIV-1, antiviral defence, promote TH1 immunity
what makes C – XCL1
made by CD8>CD4 T cells
what are the C – XCL1
receptors
CXCR1 receptors
what do C – XCL1 attract
thymocytes, dendritic cells and NK cells
C – XCL1 effects
lymphocyte trafficking and development
what are CXXXC – CX3XL1 made by
monocytes, endothelium, microglial cells
CXXXC – CX3XL1 receptor
CX3CR1 receptors
what do CXXXC – CX3XL1 attract
monocytes
T cells
CXXXC – CX3XL1 effrects
leukocyte-endothelial adhesion
brain inflammation
cytokine Production by Macrophages
usually produced transiently and locally but as can see here they also can have systemic effects….
what do activated macrophages secrete
range of cytokines
what cytokines do activated macrophages secrete
IL-1beta TNF-alpha IL-6 CXCL8 IL-12
Cytokine Production by Immune Cells
- Macrophages (innate immunity)
- Dendritic cells (innate immunity)
- T cells (adaptive immunity)
- Effect of cytokines on B cells (adaptive immunity)
Cytokine Production by DCs
Polarising ‘signal 3’ causes Th0
what makes Th1
IL-12 and IFN-gamma
what makes Th2
IL-4
what makes Th17
IL-6, TGF-beta (IL-23)
what makes Treg
IL-10, IFN-alpha, TGF-beta
Cytokine Production by T cells IL-2 – T cells
growth and differentiation
Cytokine Production by T cells IFN-gamma
macrophages activation, increase MHC 1 and 2
Cytokine Production by T cells Lymphotoxin-alpha
macrophage activates and induces NO production
Cytokine Production by T cells IL-4
B cells activation, growth IgG1, IgE, increase MHC 2 induction. T cell growth survival
Cytokine Production by T cells IL-5
hematopoietic cells increase eosinophil growth and differentiation
Cytokine Production by T cells IL-13
other tissues increase production of mucus (globet cell)
