cytokine ppt

8/10/2019 Cytokine PPT

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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.flv


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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-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
http://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Colony%20Stimulating%20Factor%20-%20YouTube.webmhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Anti%20-%20TNF%20agents.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Novel%20Agents%20for%20the%20Treatment%20of%20Crohn's%20Disease.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Novel%20Agents%20for%20the%20Treatment%20of%20Crohn's%20Disease.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Novel%20Agents%20for%20the%20Treatment%20of%20Crohn's%20Disease.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Novel%20Agents%20for%20the%20Treatment%20of%20Crohn's%20Disease.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Novel%20Agents%20for%20the%20Treatment%20of%20Crohn's%20Disease.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Anti%20-%20TNF%20agents.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Anti%20-%20TNF%20agents.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Anti%20-%20TNF%20agents.flvhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Colony%20Stimulating%20Factor%20-%20YouTube.webmhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Colony%20Stimulating%20Factor%20-%20YouTube.webmhttp://localhost/var/www/apps/conversion/tmp/Videos/RealPlayer%20Downloads/Cytokines/Colony%20Stimulating%20Factor%20-%20YouTube.webm


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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.pptx


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