CYTOKINES AND RECEPTORSChapter 12.ppt

CYTOKINES AND RECEPTORSChapter 12 What Is A Cytokine? Low molecular weight proteins (30 KDa) Bind receptors, alter gene expression Can bind the secreting cell (autocrine) Can bind another cell close by (paracrine) Few cases bind another cell far away (endocrine) Very low Kd receptors (10-10-10-12 M) Cytokines regulate immune responses Cytokines Cytokines can activate many cells Ex. Cytokines secreted by TH can affect B-cells, CTLs, M?, NK A cytokine can be pleiotropic (different effect on different cells) Synergism, redundancy, antagonism Interleukins, monokines, lymphokines, chemokines, term CYTOKINE includes all of them Cytokine Categories 4 Categories TNF family Chemokine family Interferon family Hematopoietin family Hematopoietin family ?-helical structure prevalence Little or no ?-sheet Ex. IL-2 and IL-4 Amino acid sequences vary considerably Cells That Make Cytokines And Their Function A Variety Of Cells Are Capable Of Making Cytokines However The Biggest Producers: M? and TH Cytokines Are Involved In Hematopoiesis Adaptive Immunity Innate Immunity Inflammation See Appendix For Complete List And Function Activities Established Thru Recombinant Cytokines (Simplistic Approach), In Vivo Function Can Vary Cytokines Are Non-Specific How Does Immune Specificity Fit With Non-Specific Cytokines Answer 1: Thru Receptors Receptors Expressed On Antigen Activated Cells Answer 2: Close Proximity To Cytokine Secreting Cells. Ex. APC-TH Cytokine Concentrations (TH) Are High Locally Only Interacting APC Gets Activated Answer 3: Short Half Life Short ? Life Ensures Local Activity Cytokine Receptors 5 Major Families Immunoglobulin Superfamily Hematopoietin Receptor Family (Class I) Interferon Receptor Family (Class II) TNF Receptor Family Chemokine Receptor Family Class I and II (Majority Of Receptors) Multimeric Upon Receptor Engagement, Tyrosine Phosphorylation Receptor Signalling (IFN?R) Ligand Binds ? Subunit Ligand Binding Causes Dimerization of Receptor JAKs Get Acti