Transcript Cytokines and Chemokines

Cytokines and Chemokines
Chapter 12
Karl A. Brokstad
1
2
3
Cytokines - Nomenclature
•
•
•
•
Monokines
Lymphokines
Cytokines (generic term)
interleukins
4
5
6
Cytokine actions
• Development of cellular and humoral
immune responses
• Induction of inflammation
• Regulation of hematopoiesis
• Control of cellular proliferation and
differentiation
• Induction of wound healing
• Chemotaxis
7
Main classes of cytokines
•
•
•
•
•
Interleukins (IL)
Interferons (IFN)
Chemokines (CXC, CC, C, CX3C)
Colony stimulating factors (CSF)
Tumor necrosis factors (TNF)
8
properties
•
•
•
•
•
Antagonistic
Synergistic
Redundancy
Pleiotropism
Cascade action
9
10
11
12
13
Figure 8-32
14
Cytokine receptors
•
•
•
•
•
Type I cytokine receptors
Type II cytokine receptors
IL-1 family receptors
TNF receptor
Chemokine receptors
15
16
17
18
19
20
21
22
23
24
25
26
Inflammation
• Function
• Stages
1. Deliver effector cells
2. Construct barrier
3. Repair damage
1. Recognise pathogen/damage
2. Express signalling molecules
3. Increase vascular diameter,
higher flow, lower velocity
4. Vascular permeability
5. Clothing microvessels
IL1, IL6, TNF-, INF-, IFN-, IFN-IL-8 27
28
Figure 2-15
29
Figure 2-39
30
Figure 2-46
31
Figure 2-48
32
Inflammatory cytokines
Pro-inflammatory:
IL-1, IL-6, TNF-,
IL-12, IL-18, (IFN-, chemokines)
Anti-inflammatory:
IL-4, IL-10, IL-13, TGF-
33
Chemokines
• Migration factors
34
Figure 2-41 part 1 of 2
35
Figure 2-41 part 2 of 2
36
Th1-3 Cytokines
Th1: IL-2, IFN-
Th2: IL-4, IL-5, IL-13
Th3/Tr: IL-10, TGF-
Th17: IL-17
37
38
39
CD4+ T helper cells
Cellular immunity
NK
TH0
IL-23
IL-17
TH17
Inflammation
TGF-, IL-6, IL1
IL-12, IFN-, IL-18
Humoral immunity
IL-4
M
MAST
IFN-
IFN-
IL-4
TH1
TH2
IL-4, IL-10
NK
M
IL-2, IFN-, TNF-
TC
TR1
T H3
IL-4, IL-5,
IL-6, IL-10, IL-13
CD4+ CD25+
CD4+ CD25+
FOXP3+
Regulatory actions
anti-inflammation
TGF-, IL-10
B
40
B
Proliferation cytokines
IL-2, IL-4, IL5
B
B
Diffentiating cytokines
IL-2, IL-4, IL5
IgM
IL-4
IgE / IgG1
TGF-
IgA / IgG2b
IFN-
IgG2a / IgG3
41
Functional categories
• Mediate/regulate innate immunity
– TNF, IL-1, IL-12, IFN type1, IL-10
• Mediate/regulate adaptive immunity
– IL-2, IL-4/13, IFN-γ, TGF-β
• Stimulates hematopoiesis
– development / differetiation / maturation
– IL-3, IL-7
42
43
TNF
• Innate immunity
• Acute inflammation
• Produced by monocytes/macrophages
44
45
46
47
IL-1
• Innate immunity
• Acute inflammation
• fever
IL-1α
IL-1β
IL-1RA
sIL-1R
IL-1R
48
IL-12
Innate immunity
Cell mediated immunity
MØ, act.DC
Th1  IFN-gamma
49
IFN-α + IFN-β
(type 1 IFN)
Produced by
virusinfected cells
TLR-3, 7, 9
50
51
IL-2 growth, survival, differentiation factor
52
IL-4 (+IL-13)
IgE + parasites
53
IFN-γ
54
Hematopoiesis
• IL-3  myeolid cells
• IL-7  lymphoid cells
55
56
57
58
DETECTION
stimulation
/activation
cell
measure directly in
body fluids
e.g. ELISA
transcription
translation
(mRNA)
(pre-cytokine)
nucleus
EFFECT
Signal
transduction
cytoplasm
pathway
measure expression
levels
e.g. Q-PCR
secretion
(cytokine)
measure intracellular
e.g. Flow Cytometry
59