A visual review A visual review A visual

A visual review….

A visual review….

A visual review….

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

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

Functional features • Potent – Some function at 10 -15 Molar

Functional features • Local – autocrine – paracrine – (sometimes) endocrine

Functional features • Highly interactive pleiotropic redundant synergistic antagonistic

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

Hematopoietic family Defined by architecture…

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

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…”

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’s

OK, let’s look at a complex image

And, 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 Encyclopaedia zoo of factors jungle of interactions deep morasses of acronyms bleak deserts of synonyms