PowerPoint PresentationA visual review….Slide 3Slide 4Cytokines:Functional featuresSlide 7Slide 8Slide 9Cytokine familiesHematopoietic familyInterferon family….Tumor necrosis factor…So, something’s amiss…The receptor families:Of receptors and signal transduction…What are the principal signaling systems?OK, let’s look at a complex imageAnd, an important example…And, an update…Some terms (from Horst Ibelgaufts):IMMUNOLOGYBios 328a textbook-based study of immunologySpring 2003http://www.lehigh.edu/~sk08/Courses/Bios328/mainpage.htmA visual review….A visual review….A visual review….Cytokines:•Mediators•“low” molecular weight proteins•Less than 30 kDa•Can be classified by recurrent architectureFunctional features•Potent–Some function at 10-15 Molar•Local–autocrine–paracrine–(sometimes) endocrine•Highly interactive–pleiotropic–redundant–synergistic / antagonisticFunctional features•Potent–Some function at 10-15 MolarFunctional features•Local–autocrine–paracrine–(sometimes) endocrineFunctional features•Highly interactivepleiotropicredundantsynergistic antagonisticCytokine familiesI. Hematopoietic familyII. Interferon familyIII. Tumor necrosis factor familyIV. Chemokine familyI, II, and III elicit physiological responses.IV serves as a chemoattractant.Hematopoietic familyDefined by architecture…Interferon family….http://www.hon.ch/Library/Theme/Allergy/Glossary/ifn.htmlhttp://www.ncbi.nlm.nih.gov/mapview/map_search.cgi?chr=hum_chr.inf&query=Interferon&qchr=&strain=&neighb=off&advsrch=offhttp://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570Tumor necrosis factor…•Time to be critical…•Question: What does the text say?•Answer: Not a lot.–More specifically, there is no text.–There is an entry in Table 12.1 (which stretches over four pages!) What does it say? –“Has toxic effects. Induces cytokine secretion…”So, something’s amiss…•Try another approach.•Cytokines are soluble immunomodulators.•That means that they are ligands.•Question: Can they be characterized in terms of their receptors?•Answer: Yes.The receptor families:Of receptors and signal transduction…•Receptors for cytokines have surface component, single transmembrane component, and cytoplasmic tails.•Commonly multimeric. The protomers can associate in different groupings; the various associations have different affinities for cytokines; hence, different intensities of signaling.•The different protomers also have different signaling functions, e. g. phosphorylation sites.What are the principal signaling systems? JAK’s&STAT’sOK, let’s look at a complex imageAnd, an important example…And, an update…Some terms (from Horst Ibelgaufts):cytokine network (aka: Neuroimmune network ). “This is, of course, true to the extreme: connect everything with everything in a diagram of 100 cell types and 500 factors -and add some extra lines.” Synonyms:Horst Ibelgaufts'COPE: Cytokines Online Pathfinder Encyclopaediazoo of factors jungle of interactions deep morasses of acronyms bleak deserts of