cytokine receptors komal ppt
Post on 13-Apr-2017
107 Views
Preview:
TRANSCRIPT
CYTOKINE RECEPTORS
Komal Bhanushali
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
Families5 Major Receptor Families
Immunoglobulin Super familyHematopoietin Receptor Family
(Class I)Interferon Receptor Family (Class II)TNF Receptor FamilyChemokine Receptor Family
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
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
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
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.
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.
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.
Interactions between Cytokine-specific Subunits
and a Common Signal-transducing Subunit of
Cytokine Receptors
Signaling
Competition of Ligand-binding Chains of Different Receptors for a Common Subunit Can Produce
Antagonistic Effects between Cytokines
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)
CNTF: ciliary neurotrophic factorLIF: leukemia-inhibitory factorOSM: oncostatin M
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)
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
3 Forms of the IL-2 Receptor
(CD25)
THANK YOUTHANK YOU
top related