Cytokines

الرحمن اللة الرحمن بسم اللة بسمالرحيمالرحيم

CytokinesCytokines

CytokinesCytokines

Low molecular weight Low molecular weight soluble proteinssoluble proteins (polypeptides) produced in response to (polypeptides) produced in response to microbes and other antigensmicrobes and other antigens

They act via cell surface receptors to They act via cell surface receptors to mediate mediate and regulate the amplitude and duration of and regulate the amplitude and duration of the immune-inflammatory responsesthe immune-inflammatory responses, , through activation of macrophages, through activation of macrophages, controlling growth and differentiation of T controlling growth and differentiation of T and B cellsand B cells

General Properties Of CytokinesGeneral Properties Of Cytokines

* Cytokine secretion is a self limited event (transient)* Cytokine secretion is a self limited event (transient)

* They are potent in minute amounts* They are potent in minute amounts

* One cytokine can act on different cells (pleiotropic)* One cytokine can act on different cells (pleiotropic)

* Multiple cytokines may have the same functional effects * Multiple cytokines may have the same functional effects (reduntant)(reduntant)

* Cytokines often influence synthesis and action of other * Cytokines often influence synthesis and action of other cytokinescytokines


* * Two cytokinesTwo cytokines may may antagonizeantagonize each other’s action each other’s action (produce additive or synergetic effects)(produce additive or synergetic effects)

* * ActionAction of cytokine may be of cytokine may be local or systemiclocal or systemic

* Cytokine act close to the site of production * Cytokine act close to the site of production (autocrine act.)(autocrine act.)

* Cytokine act on a nearby cell * Cytokine act on a nearby cell (paracrine action)(paracrine action)

* Large amount secretion may enter circulation and act * Large amount secretion may enter circulation and act at a distance from site of production at a distance from site of production (endocrine action)(endocrine action)


* Their action is * Their action is not antigen specificnot antigen specific

- It is initiated by - It is initiated by binding to specific cytokine binding to specific cytokine

receptorsreceptors on the membrane of target cells on the membrane of target cells

* They act as * They act as intracellular messengersintracellular messengers

* The * The response response to cytokine is:to cytokine is:

a- Expression of a- Expression of new functionsnew functions

b- b- proliferation proliferation of target cellsof target cells

Functional Categories of CytokinesFunctional Categories of Cytokines

Cytokines classifiedCytokines classified according to their biologic actions according to their biologic actions into three groups:into three groups:

1) Mediators and regulators of innate immunity1) Mediators and regulators of innate immunity

- Produced by - Produced by activatedactivated microphages and NKmicrophages and NK cells cells

in response to microbial infectionin response to microbial infection

- they act mainly on - they act mainly on endothelial cellsendothelial cells and and leukocytesleukocytes to stimulate the early inflammatory to stimulate the early inflammatory response to microbesresponse to microbes

Functional Categories of CytokinesFunctional Categories of Cytokines

2) Mediators and regulators of acquired immunity2) Mediators and regulators of acquired immunity - Produced mainly by - Produced mainly by T lymphocytesT lymphocytes in response to in response to specific recognition of foreign antigensspecific recognition of foreign antigens - They include IL-2, IL-4, IL-5,, IL-13, IFN, - They include IL-2, IL-4, IL-5,, IL-13, IFN, Transforming growth factor-Transforming growth factor-ββ (TGF- (TGF-ββ) and) and lymphotoxin (TNF- lymphotoxin (TNF- ββ))

3) Stimulators of haematopoiesis3) Stimulators of haematopoiesis - Produced by - Produced by bon marrow, stormal cells, leukocytesbon marrow, stormal cells, leukocytes - Stimulate - Stimulate growth and differentiation of leukocytesgrowth and differentiation of leukocytes - Stem cell factor, IL-3, IL-7, GM-CSF - Stem cell factor, IL-3, IL-7, GM-CSF

Interferons (IFNs)Interferons (IFNs)

* Interferons* Interferons (IFNs):(IFNs): are proteins secreted in response to are proteins secreted in response to

viral infections or other stimuliviral infections or other stimuli

* They include:* They include:

- INF-- INF-αα produced by leucocytes produced by leucocytes induced by virus infected cellsinduced by virus infected cells

-- INF-INF-ββ produced by fibroblasts produced by fibroblasts

-- INF-INF-γγ produced by NK cells,TH1 cells, CD8 T-cells produced by NK cells,TH1 cells, CD8 T-cells


Action of INF-Action of INF-αα and IFN- and IFN-ββ : :

- Prevent- Prevent viral replication viral replication

- Increase- Increase MHC-I expression on viral infected cells MHC-I expression on viral infected cells

helping their recognition by CDhelping their recognition by CD88 T-cells T-cells

-- IncreaseIncrease cytotoxic action of Nk cells cytotoxic action of Nk cells

-- InhibitInhibit cell proliferation and tumor growth cell proliferation and tumor growth


Action of IFN-Action of IFN-γγ : :

-- ActivateActivate Macrophages Macrophages

- Increase- Increase expression of MHC-I and II on APCs expression of MHC-I and II on APCs

-- EnhanceEnhance cytotoxic actions of Nk cells cytotoxic actions of Nk cells

-- PromotePromote production of TH1 and inhibits production of TH1 and inhibits

proliferation of TH2proliferation of TH2

Therapeutic Uses of CytokinesTherapeutic Uses of Cytokines

1) 1) InterferonInterferon in treatment of in treatment of viral diseases, cancerviral diseases, cancer

2) Several cytokines are used to enhance T-cell activation 2) Several cytokines are used to enhance T-cell activation in in immunofideficincy diseasesimmunofideficincy diseases, e.g. , e.g. IL-2, IFN-IL-2, IFN-,TNF-,TNF-

3) 3) IL-2 and lymphokineIL-2 and lymphokine activating killer cells (LAK)activating killer cells (LAK) in in treatment of treatment of cancercancer

4) 4) GM-CSFGM-CSF induces induces increase in white cell countincrease in white cell count, it is used:, it is used: a- To restore leukocytic count a- To restore leukocytic count after cytotoxic after cytotoxic chemotherapy induced neutropeniachemotherapy induced neutropenia b- After b- After bon marrow transplantationbon marrow transplantation C- To correct C- To correct AIDS-associated leukopeniaAIDS-associated leukopenia

Therapeutic Uses of CytokinesTherapeutic Uses of Cytokines

5) 5) Anti-cytokines antibodiesAnti-cytokines antibodies in management of in management of autoimmune diseasesautoimmune diseases and and transplant rejectiontransplant rejection:: a-a- Anti-TNF Anti-TNF in treatment in treatment rheumatoid arthritisrheumatoid arthritis b- b- Anti-IL2RAnti-IL2R to reduce to reduce graft rejectiongraft rejection

6) 6) Anti-TNF antibodiesAnti-TNF antibodies in treating in treating septic shockseptic shock

7) 7) Anti-IL-2R Anti-IL-2R in treating in treating adult T-cell leukemiaadult T-cell leukemia

8) 8) Anti-IL-4Anti-IL-4 is under trial for treatment of is under trial for treatment of allergiesallergies

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Cytokines

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