10 Cytokines Flashcards

(64 cards)

1
Q

what are cytokines

A

Secreted proteins that regulate the amplitude and duration of immune and inflammatory responses

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2
Q

where and how are cytokines usually produced

A

Usually produced transiently and locally

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3
Q

what are cytokines like

A

Extremely potent

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4
Q

what do cytokines bind to

A

Bind to specific cell-surface receptors

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5
Q

effect of cytokine

A

Change cell behaviour (signal into cell and cause change)

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6
Q

what are the normal levels of cytokine used for

A

health

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7
Q

what are the increasing levels of cytokine used for

A

At increasing levels important for disease conditions e.g. toxic shock, sepsis and organ failure

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8
Q

why are cytokines so important

A

They regulate all the important biological processes

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9
Q

Cytokine action

A
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
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10
Q

GF

A

growth factors

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11
Q

CSF

A

colony stimulating factors

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12
Q

Cytokine families

A

Hematopoietin family
TNF family
Interferon family
Chemokine family

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13
Q

Hematopoietins cytokine family

A

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

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14
Q

class 1 cytokine receptor (hematopoietin-receptor family) - IL-3, IL-5 and GM-CSF

A

share a common beta receptor chain and the alpha chain is different in each case

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15
Q

class 1 cytokine receptor (hematopoietin-receptor family) - IL-2, IL-4. IL-7. IL-9 and IL-15

A

have a common gamma chain, beta chain differs for each receptor. IL-2 has a third chain, high-affinity subunit IL-2R alpha (CD25)

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16
Q

class 1 cytokine receptor (hematopoietin-receptor family)

A

just have alpha or beta receptors for erythropoietin, growth hormone and IL-13

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17
Q

IL-2 actions

A

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

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18
Q

IL-2 production

A

It is produced by Th cells

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19
Q

TNF cytokine family

A

TNF-alpha

TNF-beta

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20
Q

how do TNF cytokine family naturally occur

A

Ribbon representation of TNF family cytokines - they occur naturally as trimers (TOP)

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21
Q

what is the monomeric TNF bound to

A

Monomeric TNF bound to one subunit of TNF receptor (BOTTOM)

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22
Q

what group of receptors are TNF receptor in

A

Tnf receptors are members of large group of G protein coupled receptors

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23
Q

Cell activation by TNF

A

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

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24
Q

Actions of TNF

A
  • 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
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25
Interferon cytokine family
Interferon-alpha Interferon-beta Interferon - gamma IL-10
26
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
27
what makes IFN-gamma
Made by T and NK cells
28
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
29
negative action of IFN-gamma
Inhibits haemopoiesis, anti-proliferative and antiviral
30
which IFN is most potent
IFN-gamma is less potent at antiviral and antiproliferative activities than INF-alpha and beta
31
Chemokine and chemokine receptor family
7 transmembrane spanning domains – cytokine receptors
32
Chemokine Groups
Grouped into different sets
33
IL-8
chemoattractant for neutrophils - migrate to site of damage
34
where are CXC – CXCL13 (BLC) made
stromal cells
35
what are the CXC – CXCL13 (BLC) receptors
CXCR5 receptors
36
what do CXC – CXCL13 (BLC) attract
attract B cells
37
CXC – CXCL13 (BLC) effect
lymphocyte homing
38
where are CC – CCL3 made
produced by macrophages, T cells, mast cells, fibroblasts
39
CC – CCL3 receptors
CCR1,3,5
40
what do CC – CCL3 attract
monocytes NK and T cells basophils dendritic cells
41
CC – CCL3 effects
competes with HIV-1, antiviral defence, promote TH1 immunity
42
what makes C – XCL1
made by CD8>CD4 T cells
43
what are the C – XCL1 | receptors
CXCR1 receptors
44
what do C – XCL1 attract
thymocytes, dendritic cells and NK cells
45
C – XCL1 effects
lymphocyte trafficking and development
46
what are CXXXC – CX3XL1 made by
monocytes, endothelium, microglial cells
47
CXXXC – CX3XL1 receptor
CX3CR1 receptors
48
what do CXXXC – CX3XL1 attract
monocytes | T cells
49
CXXXC – CX3XL1 effrects
leukocyte-endothelial adhesion | brain inflammation
50
cytokine Production by Macrophages
usually produced transiently and locally but as can see here they also can have systemic effects….
51
what do activated macrophages secrete
range of cytokines
52
what cytokines do activated macrophages secrete
``` IL-1beta TNF-alpha IL-6 CXCL8 IL-12 ```
53
Cytokine Production by Immune Cells
- Macrophages (innate immunity) - Dendritic cells (innate immunity) - T cells (adaptive immunity) - Effect of cytokines on B cells (adaptive immunity)
54
Cytokine Production by DCs
Polarising ‘signal 3’ causes Th0
55
what makes Th1
IL-12 and IFN-gamma
56
what makes Th2
IL-4
57
what makes Th17
IL-6, TGF-beta (IL-23)
58
what makes Treg
IL-10, IFN-alpha, TGF-beta
59
Cytokine Production by T cells IL-2 – T cells
growth and differentiation
60
Cytokine Production by T cells IFN-gamma
macrophages activation, increase MHC 1 and 2
61
Cytokine Production by T cells Lymphotoxin-alpha
macrophage activates and induces NO production
62
Cytokine Production by T cells IL-4
B cells activation, growth IgG1, IgE, increase MHC 2 induction. T cell growth survival
63
Cytokine Production by T cells IL-5
hematopoietic cells increase eosinophil growth and differentiation
64
Cytokine Production by T cells IL-13
other tissues increase production of mucus (globet cell)