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What Is A Cytokine? Low sub-atomic weight proteins (30 KDa) Bind receptors, change quality expression Can tie the emitting cell (autocrine) Can tie another cell close by (paracrine) Few cases tie another cell far away (endocrine) Very low K d receptors (10 - 10 - 10 - 12 M) Cytokines manage invulnerable reactions

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Cytokines can enact numerous cells Ex. Cytokines emitted by T H can influence B-cells, CTLs, M  , NK A cytokine can be pleiotropic (distinctive impact on various cells) Synergism, excess, opposition Interleukins, monokines, lymphokines, chemokines, term CYTOKINE incorporates every one of them

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Cytokine Categories 4 Categories TNF family Chemokine family Interferon family Hematopoietin family Hematopoietin family -helical structure predominance Little or no  - sheet Ex. IL-2 and IL-4 Amino corrosive arrangements differ impressively

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Cells That Make Cytokines And Their Function A Variety Of Cells Are Capable Of Making Cytokines However The Biggest Producers: M  and T H 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

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Cytokines Are Non-Specific How Does Immune Specificity Fit With Non-Specific Cytokines Answer 1: Thru Receptors Expressed On Antigen Activated Cells Answer 2: Close Proximity To Cytokine Secreting Cells. Ex. APC-T H Cytokine Concentrations (T H ) Are High Locally Only Interacting APC Gets Activated Answer 3: Short Half Life Short ½ Life Ensures Local Activity

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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

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Hematopoietin Receptor Family (Class I)

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Receptor Signaling (IFN  R) Ligand Binds  Subunit Ligand Binding Causes Dimerization of Receptor JAKs Get Activated Phosphorylation of tyrosine deposits on receptor Phosphorylation of JAKs themselves STATS Dock Receptor Phosphorylation of STATs by JAKs Dimerized STATs Translocate To Nucleus Gene Expression

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Cytokine Antagonists Exist In 2 Forms Receptor Antagonists (Bind Receptor, No Activation) Bind Cytokine (Prevent Cytokine From Binding Receptor) Well Studied Example: IL1Ra In Many Cases Antagonist Is A Soluble Receptor Derived From Proteolytic Cleavage Of Extracellular Domain Of Particular Receptor IL-2, IL-4, IFN  , IFN  Viruses Produce Cytokine Mimics Or Cytokine Binding Proteins Ex. Poxviruses Produce IL-1-Binding Protein And TNF-restricting protein These Agents Offer Viruses An Advantage

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T H 1 versus T H 2 CD4 + T H Cells Secret A Variety Of Cytokines Evidence For 2 Subsets T H 1 T H 2 Distinction Is Based On Cytokine Secretion Cytokine Environment Determines Which Subset Will Develop IFN  for T H 1 (IL-12 and IL-18 from M ,DCs ) IL-4 for T H 2

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Transcription Factors T H 1 And T H 2 T-wager Expression Results In T H 1 T-wager Suppresses T H 2 GATA-3 Results In T H 2 GATA-3 Suppresses T H 1 IFN- Regulates Expression of T-wager (Stat 1) IL-4 Regulates Expression of GATA-3 (Stat 6)