Functions Receptors Signaling Chapter 11 Cytokines Functions Receptors Signaling Chapter 11 Cut back on chemokine stuff Dave gives a lot of that in the prior lecture Focus on signaling pathways Add more on Th1/Th2

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

Functions of cytokines stimulation inhibition differentiation cell death chemoattract

Properties of cytokines Abbas Figure 11-2

Key Cytokines Produced by Innate Immune Responses IL-1 - macrophages, epithelial cells IL-6 - macrophages, endothelial cells (also T cells) IL-12 - macrophages, dendritic cells TNF-a - macrophages, NK cells (also T cells) IFN-a - dendritic cells, virally infected cells IFN-b - virally infected cells

Functions of cytokines in innate immunity Abbas Figure 11-1A

The release of TNF-a by macrophages induces local protective effects, but TNF-a can have damaging effects when released systemically (septic shock). Abbas Figure 11-5

Antiviral effects of Type I Interferons (IFN-a/b) Abbas Figure 11-8

Key Cytokines Produced by T Cells IL-2 - CD8+, naïve and Th1 CD4+ cells IFNg - CD8+, Th1 CD4+ TNF-a - CD8+, Th1 and some Th2 CD4+ IL-4 - Th2 CD4+ 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

JAK-Janus kinase STAT-signal transducer and activator of transcription 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/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