1. 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

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

3. Functions of cytokines
stimulation
inhibition
differentiation
cell death
chemoattract

4. Properties of cytokines
Abbas Figure 11-2

5. 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

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

7. 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

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

9. 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

10. Functions of cytokines in acquired immunity
Abbas
Figure 11-1B

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

13. Cytokine receptors subfamilies have shared signaling subunits (see also Abbas Figure 11-3B).

14. Cytokine receptor function is regulated by expression of the subunits - the IL-2R story
See also Abbas
Figure 11-11

15. 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

16. JAK/STATs Used by Key Cytokines
See also Abbas
Box 11-2 Table

17. 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)

18. Abbas Figure 11-6

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