10 Cytokines Flashcards

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
Q

Interferon cytokine family

A

Interferon-alpha
Interferon-beta
Interferon - gamma
IL-10

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26
Q

Cell activation by IFN-alpha

A

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
Q

what makes IFN-gamma

A

Made by T and NK cells

28
Q

Actions of IFN-gamma

A

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
Q

negative action of IFN-gamma

A

Inhibits haemopoiesis, anti-proliferative and antiviral

30
Q

which IFN is most potent

A

IFN-gamma is less potent at antiviral and antiproliferative activities than INF-alpha and beta

31
Q

Chemokine and chemokine receptor family

A

7 transmembrane spanning domains – cytokine receptors

32
Q

Chemokine Groups

A

Grouped into different sets

33
Q

IL-8

A

chemoattractant for neutrophils - migrate to site of damage

34
Q

where are CXC – CXCL13 (BLC) made

A

stromal cells

35
Q

what are the CXC – CXCL13 (BLC) receptors

A

CXCR5 receptors

36
Q

what do CXC – CXCL13 (BLC) attract

A

attract B cells

37
Q

CXC – CXCL13 (BLC) effect

A

lymphocyte homing

38
Q

where are CC – CCL3 made

A

produced by macrophages, T cells, mast cells, fibroblasts

39
Q

CC – CCL3 receptors

A

CCR1,3,5

40
Q

what do CC – CCL3 attract

A

monocytes
NK and T cells
basophils
dendritic cells

41
Q

CC – CCL3 effects

A

competes with HIV-1, antiviral defence, promote TH1 immunity

42
Q

what makes C – XCL1

A

made by CD8>CD4 T cells

43
Q

what are the C – XCL1

receptors

A

CXCR1 receptors

44
Q

what do C – XCL1 attract

A

thymocytes, dendritic cells and NK cells

45
Q

C – XCL1 effects

A

lymphocyte trafficking and development

46
Q

what are CXXXC – CX3XL1 made by

A

monocytes, endothelium, microglial cells

47
Q

CXXXC – CX3XL1 receptor

A

CX3CR1 receptors

48
Q

what do CXXXC – CX3XL1 attract

A

monocytes

T cells

49
Q

CXXXC – CX3XL1 effrects

A

leukocyte-endothelial adhesion

brain inflammation

50
Q

cytokine Production by Macrophages

A

usually produced transiently and locally but as can see here they also can have systemic effects….

51
Q

what do activated macrophages secrete

A

range of cytokines

52
Q

what cytokines do activated macrophages secrete

A
IL-1beta
TNF-alpha
IL-6
CXCL8
IL-12
53
Q

Cytokine Production by Immune Cells

A
  • Macrophages (innate immunity)
  • Dendritic cells (innate immunity)
  • T cells (adaptive immunity)
  • Effect of cytokines on B cells (adaptive immunity)
54
Q

Cytokine Production by DCs

A

Polarising ‘signal 3’ causes Th0

55
Q

what makes Th1

A

IL-12 and IFN-gamma

56
Q

what makes Th2

A

IL-4

57
Q

what makes Th17

A

IL-6, TGF-beta (IL-23)

58
Q

what makes Treg

A

IL-10, IFN-alpha, TGF-beta

59
Q

Cytokine Production by T cells IL-2 – T cells

A

growth and differentiation

60
Q

Cytokine Production by T cells IFN-gamma

A

macrophages activation, increase MHC 1 and 2

61
Q

Cytokine Production by T cells Lymphotoxin-alpha

A

macrophage activates and induces NO production

62
Q

Cytokine Production by T cells IL-4

A

B cells activation, growth IgG1, IgE, increase MHC 2 induction. T cell growth survival

63
Q

Cytokine Production by T cells IL-5

A

hematopoietic cells increase eosinophil growth and differentiation

64
Q

Cytokine Production by T cells IL-13

A

other tissues increase production of mucus (globet cell)