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A visual review….

A visual review…. A visual review…. A visual review…. Cytokines:. Mediators “low” molecular weight proteins Less than 30 kDa Can be classified by recurrent architecture. Functional features. Potent Some function at 10 -15 Molar Local autocrine paracrine (sometimes) endocrine

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A visual review….

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  1. A visual review….

  2. A visual review….

  3. A visual review….

  4. Cytokines: • Mediators • “low” molecular weight proteins • Less than 30 kDa • Can be classified by recurrent architecture

  5. Functional features • Potent • Some function at 10-15 Molar • Local • autocrine • paracrine • (sometimes) endocrine • Highly interactive • pleiotropic • redundant • synergistic / antagonistic

  6. Functional features • Potent • Some function at 10-15 Molar

  7. Functional features • Local • autocrine • paracrine • (sometimes) endocrine

  8. Functional features • Highly interactive pleiotropic redundant synergistic antagonistic

  9. Cytokine families • Hematopoietic family • Interferon family • Tumor necrosis factor family • Chemokine family I, II, and III elicit physiological responses. IV serves as a chemoattractant.

  10. Hematopoietic family Defined by architecture…

  11. Interferon family…. http://www.hon.ch/Library/Theme/Allergy/Glossary/ifn.html http://www.ncbi.nlm.nih.gov/mapview/map_search.cgi?chr=hum_chr.inf&query=Interferon&qchr=&strain=&neighb=off&advsrch=off http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570

  12. Tumor 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…”

  13. 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.

  14. The receptor families:

  15. 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.

  16. What are the principal signaling systems? JAK’s & STAT’s

  17. OK, let’s look at a complex image

  18. And, an important example…

  19. And, an update…

  20. 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 Encyclopaedia zoo of factors jungle of interactions deep morasses of acronyms bleak deserts of synonyms

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