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CYTOKINE RECEPTORS Komal Bhanushali
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Cytokine receptors KOMAL ppt

Apr 13, 2017

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Page 1: Cytokine receptors KOMAL ppt

CYTOKINE RECEPTORS

Komal Bhanushali

Page 2: Cytokine receptors KOMAL ppt

IntroductionLow molecular weight compounds (<30KDa).Regulate the intensity and duration of immune

response by exerting a variety of effects on lymphocytes & other immune cells.

They are messengers of immune system They mediate biological effects at picomolar

concentrationsFunction mostly by autocrine & paracrine actionInterleukins, monokines, lymphokines,

chemokines,term CYTOKINE include all of them.Cytokines exert their biological effects by

binding to specific receptors expressed on the membrane of responsive target cells

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Families5 Major Receptor Families

Immunoglobulin Super familyHematopoietin Receptor Family

(Class I)Interferon Receptor Family (Class II)TNF Receptor FamilyChemokine Receptor Family

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Immunoglobulin Super FamilyStructure identical to

immunoglobulin'sReceptors for IL-1,IL-18Role of IL-1:-InflammationReceptors for IL-1 are of two

types :- type1 IL-1R-expressed on many

cells type2 IL-1R-limited to B cells

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Hematopoietin Receptor Family(Class 1)Members:-Receptors that function in

immune and hematopoietic systems.Features:-Conserved amino acid sequence

motif in extra cellular domain consisting of 4 cysteines (CCCC) & WSXWS.

Ligands:- -All cytokines classified as hematopoietins -IL2 &1L3 other ILs -Several CSF -Growth hormones

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Interferon Receptor Family(Class II)Features:-Conserved CCCC but lack

WSXWS .Family consists of 12 receptor chains that

in their various assortments bind to various cytokines

Ligands:-more than 27 different cytokines including- IFNα,β,γ plus 17 type1 IFNs

-1 type II IFN -3 types of IFN λ -6 members of IL10 family

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Subfamilies of Class I cytokine receptorsHave multiple subunits, often including

one subunit that binds to specific cytokine and other that mediates signal transduction.

3 Subfamilies described here:- i)GM-CSF ii)IL2 iii)IL6Exhibit redundancy and antagonism due

to sharing of signal transducing subunit.

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1)GM-CSF Receptor Subfamily Common signal transducing

subunit is β subunit & cytokines bind with low affinity to α subunit.

Includes receptors for:- 1)IL3 2)IL5 3)GM-CSF Dimeric receptors.

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CONTD… Redundancy :-as β subunit is common.

• IL-3 &GM-CSF together will act on hematopoietic stem cells ,progenitor cells, activate monocytes and induce megakaryocyte differentiation.• IL-3, GM-CSF, IL-5 all these three together will

induce eosinophil proliferation , basophil degranulation with release of histamine

Antagonism:-as they compete for limited number of β subunits.

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Interactions between Cytokine-specific Subunits

and a Common Signal-transducing Subunit of

Cytokine Receptors

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Signaling

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Competition of Ligand-binding Chains of Different Receptors for a Common Subunit Can Produce

Antagonistic Effects between Cytokines

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2)IL6 Receptor SubfamilyCommon signal transducing subunit is

gp130 associated with one or two different types of cytokine specific subunits

Includes receptors for:- 1)IL-6 2)IL-11 3)LIF(Leukemia Inhibitory Factor) 4)OSM (Oncostatin M) 5)CNTF (Ciliary Neurotrophic Factor)

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CNTF: ciliary neurotrophic factorLIF: leukemia-inhibitory factorOSM: oncostatin M

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3)IL-2 Receptor Subfamily Common signaling subunit is γ Includes receptors for :- 1)IL2 2)IL4 3)IL7 4)IL9 5)IL15 6)IL21 IL2&IL15 are heterotrimers rest all are dimers Defect in γ chain gene leads to XSCID(X-Linked

Severe Combined Immuno Deficiency)

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CONTD…IL2R main role:-clonal

proliferation of T cells.IL2 occurs in 3 forms :- 1)low affinity monomeric IL-2Rα 2)Intermediate affinity dimeric IL-2Rβγ 3)High affinity trimeric IL-2Rαβγ

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3 Forms of the IL-2 Receptor

(CD25)

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THANK YOUTHANK YOU