Cytokines and Chemokines

Chapter 12

Karl A. Brokstad

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Cytokines - Nomenclature

• Monokines

• Lymphokines

• Cytokines (generic term)

• interleukins

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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

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Main classes of cytokines

• Interleukins (IL)

• Interferons (IFN)

• Chemokines (CXC, CC, C, CX3C)

• Colony stimulating factors (CSF)

• Tumor necrosis factors (TNF)

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properties

• Antagonistic

• Synergistic

• Redundancy

• Pleiotropism

• Cascade action

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Figure 8-32

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Cytokine receptors

• Type I cytokine receptors

• Type II cytokine receptors

• IL-1 family receptors

• TNF receptor

• Chemokine receptors

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Inflammation• Function1. Deliver effector cells

2. Construct barrier

3. Repair damage

• Stages1. Recognise pathogen/damage2. Express signalling molecules3. Increase vascular diameter,

higher flow, lower velocity4. Vascular permeability5. Clothing microvessels

IL1, IL6, TNF-, INF-, IFN-, IFN-IL-8 27

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Figure 2-15

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Figure 2-39

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Figure 2-46

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Figure 2-48

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Pro-inflammatory: IL-1, IL-6, TNF-, IL-12, IL-18, (IFN-, chemokines)

Anti-inflammatory: IL-4, IL-10, IL-13, TGF-

Inflammatory cytokinesInflammatory cytokines

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Chemokines

• Migration factors

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Figure 2-41 part 1 of 2

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Figure 2-41 part 2 of 2

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Th1: IL-2, IFN-

Th2: IL-4, IL-5, IL-13

Th3/Tr: IL-10, TGF-

Th17: IL-17

Th1-3 Cytokines Th1-3 Cytokines

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4040

TH0

TH1

TH3IL-2, IFN-, TNF- IL-4, IL-5,

IL-6, IL-10, IL-13

TGF-, IL-10

TH2

IFN-

IL-4, IL-10

NK

M

IL-12, IFN-, IL-18

MAST

IL-4

NK

MTC

CD4+ T helper cells

TR1

CD4+ CD25+CD4+ CD25+FOXP3+

Cellular immunity

Humoral immunity

B

IL-4IFN-

TH17IL-17

Inflammation

Regulatory actionsanti-inflammation

TGF-, IL-6, IL-1

IL-23

B

B B

IgM IgE / IgG1 IgA / IgG2b IgG2a / IgG3

Proliferation cytokinesIL-2, IL-4, IL5

IL-2, IL-4, IL5 IL-4 TGF- IFN-

Diffentiating cytokines

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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

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TNF

• Innate immunity

• Acute inflammation

• Produced by monocytes/macrophages

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IL-1

• Innate immunity

• Acute inflammation

• fever

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IL-1αIL-1α

IL-1RAIL-1RA sIL-1RsIL-1R

IL-1RIL-1R

IL-1βIL-1β

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IL-12

Innate immunity

Cell mediated immunity

MØ, act.DC

Th1 IFN-gamma

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IFN-α + IFN-β(type 1 IFN)

Produced by virusinfected cells

TLR-3, 7, 9

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IL-2 growth, survival, differentiation factor

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IL-4 (+IL-13)

IgE + parasites

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IFN-γ

Hematopoiesis

• IL-3 myeolid cells

• IL-7 lymphoid cells

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cell

cytoplasm

nucleus

stimulation/activation

Signal transduction pathway

transcription(mRNA) translation

(pre-cytokine)

secretion(cytokine)

measure directly in body fluids

e.g. ELISA

measure intracellular

e.g. Flow Cytometry

measure expression levelse.g. Q-PCR

EFFECT

DETECTION

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