Post on 02-Jun-2018
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IRAM KHALIQ
SARA HINA SIDRA
Pharmacology Therapeutics-III
SIR IMRAN ARSHAD
Semester:1
M PHIL
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CHEMICAL MEDIATORS
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These are endogenous chemicalsubstances that are released from cells orplasma or the damaged tissue itself, to
mediate & partake in various processes ofacute inflammation like vasodilatation,increased vascular permeability, PMN
chemotaxis, fever, pain, tissue damage
etc
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DEFINITION
The term "cytokine" is derived from a
combination of two Greek words - "cyto"
meaning cell and "kinos" meaning
movement.Cytokines are cell signalling molecules
that aid cell to cell communication in
immune responses and stimulate themovement of cells towards sites of
inflammation, infection and trauma.
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Cytokines exist in peptide, proteinand
glycoprotein (proteins with a sugar
attached) forms.
The cytokines are a large family of
molecules that are classified in various
different ways due to an absence of aunified classification system.
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Functions of cytokines
Stimulation
Inhibition
Differentiation
Cell death
chemoattract
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Cytokine actions may be characterizedas:
Autocrine(self modulating)
Paracrine(modulating cells in theimmediate surroundings)
Endocrine(modulating cells throughcirculation in the distant area)
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Properties of cytokines
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Names of Cytokines
Source
e.g.,Lymphokines
Funct ion
e.g.,Chemokines
In tercel lular act ion
e.g., Interleukins
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Chain of Cytokine Action
Stimulus>Cytokine-
producing cell>
Cytokine>Target
cel l>Receptor>
B iolog ical effect(s)
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Cytokine-generating Cells
A Variety Of Cells AreCapable Of MakingCytokines
However The BiggestProducers: Mand
TH
Innate immunity Macrophages
Endothelial cells
Fibroblasts
Adaptive immunity T lymphocytes
Macrophages
NK cellsTHI TH2
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FUNCTIONAL CLASSES OFCYTOKINESCytokines classified according to their biologic
actions into three groups:
1) Mediators and regulators of innate immunity
- Produced by activatedmacrophages andNKcells in response to microbial infection
- they act mainly on endothelial cellsandleukocytesto stimulate the early
inflammatory response to microbes
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2) Mediators and regulators of acquiredimmunity
- Produced mainly by T lymphocytesinresponse tospecific recognition of foreign antigens
- They include IL-2, IL-4, IL-5,, IL-13, IFN,Transforming growth factor-(TGF-) andlymphotoxin (TNF- )
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3) Stimulators of haematopoiesis
- Produced by bone marrow, stormal cells,
leukocytes- Stimulate growth and differentiation ofleukocytes- Stem cell factor, IL-3, IL-7, GM-CSF
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1) Interferons (IFNs)
* Interferons (IFNs):are proteins secreted inresponse to viral infections or other stimuli
* They include:
- INF-produced by leucocytesinduced by virus infected
cells
-INF-produced by fibroblasts
-INF-produced by NK cells,TH1 cells, CD8T-cells
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Action of INF- and IFN-:- Preventviral replication
- IncreaseMHC-I expression on viralinfected cells helping their recognitionby CD8 T-cells
-Increasecytotoxic action of Nk cells
-Inhibitcell proliferation and tumorgrowth
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Action of IFN-:
-ActivateMacrophages
- Increaseexpression of MHC-I and II onAPCs
-Enhancecytotoxic actions of Nk cells
-Promoteproduction of TH1 and inhibitsproliferation of TH2
http://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Interferon%20and%20how%20it%20works%20in%20the%20body.%20-%20YouTube.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Interferon%20and%20how%20it%20works%20in%20the%20body.%20-%20YouTube.flv8/10/2019 Cytokine PPT
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2) Interleukins
Group of cytokines(secreted proteins/signallingmolecules) that were first seen to be expressedby white blood cells (leukocytes).
The function of the immune systemdepends in alarge part on interleukins. The majority ofinterleukins are synthesized by helper CD4+ Tlymphocytes, as well as through monocytes,macrophages, and endothelial cells.
They promote the development anddifferentiation of T, B, and hematopoietic cells.
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3)Tumor necrosis factors(TNF) Group of cytokines which can cause cell
death (Apoptosis).
Family members :- 19 cytokines are
identified as part of the TNF family on thebasis of sequence, functional & structuresimilarities.
The first two members of the family to beidentified were;
TNF- TNF-
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4) Transforming growthfactor (TGF) Sometimes referred to as Tumor Growth
Factor.
Two classes of polypeptide growth factors,
TGF - & TGF .
The two classes of TGFs are not structurallyor genetically related to one another & theyact through different receptor mechanisms.
They dont always inducecellulartransformation, and are not the only growthfactors that induce cellular transformation.
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5) Colony stimulating factors(CSFs) colony-stimulating factors are soluble,
membrane-bound substances ofthe hematopoietic microenvironment.
secreted glycoproteins that bind toreceptor proteins on the surfaces
of hemopoietic stem cells.
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6) Growth factor
A naturally occurring substance capableof stimulating cellular growth,proliferation & cellular differentiation.
Usually it is a protein or a steroidhormone.
Growth factors are important forregulating a variety of cellular processes.
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CHEMOKINES
Family of chemoattractants forinflammatory cells & include;
IL-8 chemotactic for neutrophils
Platelet factor 4 chemotactic forneutrophils, monocytes & eosinophils
MCP 1 chemotactic for monocytes
Eotaxin chemotactic for eosinophils
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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
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Cytokine Receptors
Multimeric receptors
Common signal-transducing subunits
Unique high affinity subunits
High affinity subunits associated with
activation of target cell
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Seven-transmembrane-domain receptorssignal by coupling with trimeric GTP-
binding proteins
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Signal Transduction
Initiated by cytokine binding
Activates JAK (Janus kinase)
Phosphorylation of tyrosine
Binding of STAT(Signal transducers and
activators of transcription)
Translocation of STAT to cells DNA
Transcription of specific target genes
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Ligand Binds Subunit Ligand Binding Causes
Dimerization of Receptor
JAKs Get Activated Phosphorylation of tyrosine residues
on receptor Phosphorylation of JAKs themselves
STATS Dock Receptor Phosphorylation of STATs by JAKs
Dimerized STATs Translocate ToNucleus
Gene Expression
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Role of Cytokines in Hematopoiesis
SCF (Stem cell factor)
GM-CSF (Granulocyte-macrophage
colony-stimulating factor)
IL-3 (Interleukin 3)
IL-5 (Interleukin 5)
IL-7 (Interleukin 7)
IL-11(Interleukin 11)
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Therapeutic Uses of Cytokines
1) Interferon in treatment of viral diseases,cancer.
2) Several cytokines are used to enhance T-cell
activation in immunofideficincy diseases, e.g.IL-2, IFN-,TNF-.
3) IL-2 and lymphokine activating killer cells (LAK)
in treatment of cancer.
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4) GM-CSF induces increase in white cell count, it is used:
a- To restore leukocytic count after cytotoxic
chemotherapy induced neutropenia
b- After bon marrow transplantation
C- To correct AIDS-associated leukopenia
5) Anti-cytokines antibodies in management of
autoimmune diseases and transplant rejection:
a- Anti-TNFin treatment rheumatoid arthritis
& Crohnsdisease.
b- Anti-IL2R to reduce graft rejection
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6) Anti-TNF antibodies in treating septic
shock
7) Anti-IL-2R in treating adult T-cellleukemia
8) Anti-IL-4 is under trial for treatmentof allergies
C ki b d h i i li i l
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Cytokines based therapies in clinicaluse
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**(Knowledge is an unending adventure at the edge ofuncertainity) **
Pharmacology. H. P. Rang, M. M.Dale, J. M. Ritter & P. K. Moore
http://www.cytokines.com/
http://en.wikipedia.org/wiki/Cytokine
Pathological Basis ofDisease. Robbins & Cotran
Essential of medicalpharmacology. K. D. Tripathi
REFERANCES
http://www.cytokines.com/http://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Cytokinehttp://www.cytokines.com/http://www.cytokines.com/http://www.cytokines.com/http://www.cytokines.com/http://www.cytokines.com/http://localhost/var/www/apps/conversion/tmp/Documents/Questions.pptx8/10/2019 Cytokine PPT
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http://localhost/var/www/apps/conversion/tmp/Documents/Questions.pptx