CytokinesFunctions

Receptors

SignalingChapter 11

Cytokines are soluble mediators (small proteins) of innate and adaptive immunity and the mechanisms by which leukocytes communicate with

one another.

Functions of cytokines

stimulationinhibition

differentiationcell death

chemoattract

Properties of cytokines

Abbas Figure 11-2

Key Cytokines Produced by Innate Immune Responses

1) IL-1 - macrophages, epithelial cells

2) IL-6 - macrophages, endothelial cells (also T cells)

3) IL-12 - macrophages, dendritic cells

4) TNF- - macrophages, NK cells (also T cells)

5) IFN- - dendritic cells, virally infected cells

6) IFN- - virally infected cells

Functions of cytokines in innate immunity

Abbas Figure 11-1A

The release of TNF- by macrophages induces local protective effects, but TNF- can have damaging effects when released systemically (septic shock).

Abbas Figure 11-5

Antiviral effects of Type I Interferons (IFN-/)

Abbas Figure 11-8

Key Cytokines Produced by T Cells

1) IL-2 - CD8+, naïve and Th1 CD4+ cells

2) IFN - CD8+, Th1 CD4+

3) TNF- - CD8+, Th1 and some Th2 CD4+

4) IL-4 - Th2 CD4+

5) IL-10 - Th2 CD4+

See also Table 11-4

Functions of cytokines in acquired immunity

Abbas Figure 11-1B

Cytokine receptors belong to families of receptor proteins, each with a distinctive structure (See also Abbas Figure 11-3A).

Cytokine receptors subfamilies have shared signaling subunits (see also

Abbas Figure 11-3B).

Cytokine receptor function is regulated by expression of the subunits - the IL-2R story

See also Abbas Figure 11-11

Class I and Class II cytokine receptors signal by a rapid pathway using receptor-associated kinases to activate specific transcription factors.

Abbas Box 11-2

JAK-Janus kinase

STAT-signal transducer and activator of transcription

JAK/STATs Used by Key Cytokines

See also Abbas Box 11-2 Table

Chemokines are a family of proteins of similar structure that bind to chemokine receptors, members of a large family of G protein-coupled receptors.

CXCL8

Rhodopsin bound to ligand retinal (structure predicted to be similar to chemokine receptor)

Abbas Figure 11-6

Seven-transmembrane-domain receptors signal by coupling with trimeric GTP-binding proteins