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Class Seminar Paper : Immunology

Topic : Cytokine and their roles in the


immune regulation
Submitted
By:
MD. JIYAUL MUSTAFA
(M.Sc. Biotech. IInd Sem.)

DEPARTMENT OF BIOTECHNOLOGY
Contents

Introduction
Properties of Cytokines
Cytokine receptor
Signaling pathway
Regulation of cytokine
Cytokine releated Diseases
References
Introduction
 Cytokines are low molecular weight regulatory protein
or glycoprotein secreted by WBC and various other
cells in the body in response to a number of stimuli.

 Cytokines play role in the cell to cell communication


between lymphoid cell, inflammatory cells and
hemtopoietic cells for effective immune response.

 cytokines bind to specific receptor on the membrane of


target cell, triggering signal transduction pathways that
ultimately alter gene expression in the target cells.
 Cytokines regulate the intensity and duration of
immune response by stimulating or inhibiting the
activation and by regulating the secretion of antibodies
or other cytokines.

 Cytokines produced by activated TH cells can


influences the activity of B cells, Tc cells, NK cells,
Macrophages, granulocytes and hematopoietic stem
cells.
Properties of cytokines :

Pleiotropic action : A given cytokines that has different biological


effects on different target cells.

Redundancy : two or more cytokines that mediate similar function.

Synergy : the combined effects of two cytokines or celluar activity is


greater than the additive effects of the individual cytokines.

Antagonism : The effects of one cytokines inhibits or offset of


another cytokines.

Cascade induction : when the action of one cytokines on a target


cell induces that cell to produce one or more other cytokines , which
in turn induce other target cells to produce other cytokines.
Cytokines are referred as interleukins.

Interleukins 1-25 have been identified.

Cytokines generally have a molecular mass of less than


30 kDa.

Cytokines are groped into four classes:

1) Hematpoietic family
2) Interferon family
3) chemokine family
4) tumor necrosis factor family
 TH cell and Macrophage are the two principal
producers of cytokines.

 Cytokines released from these two cells activate an


entire network of interacting cells.

 Cytokines involve in:

 Development of cellular and humoral immune respones,


 inductions of inflammatory response,
 Regulation of hematopoiesis
 Control of celluar proliferation and differentiation
 Healing of wound.
Cytokine receptor
 receptor for the cytokines are quite diverse structure.

There are five family of cytokine receptor :

I. Immunoglobulin superfamily receptor

II. Class I cytokine receptor family (hematopioetin receptor family)

III. Class II cytokine receptor family ( Interferon receptor family)

IV. TNF receptor family

V. Chemokine receptor family


Signaling Pathway

Cytokine binding induces the association of the two


seperate cytokine receptor subunit and activation of
the receptor associated JAKs

Activated JAKs create docking sites for the STAT


transcription factor by phosphorylation of specific
tyrosine residues on cytokine receptor subunit.

After undergoing JAK – mediated phosphorylation


STAT transcription factors translocate from receptor
docking sites at the membrane to the nucleus where they
initiate the transcription of specific gene.
Cytokine regulation

Cytokine secretion by TH1 and TH2 subsets.

The TH1 subset is responsible for many cell- mediated


function (delayed – type hypersensitivity and activation
of Tc Cell) and for the production of antibodies.

This subset is also associated with the promotion of


excessive inflammation and tissue injury.
The TH2 subset stimulate Eosinophil activation and differention ,
provides help to B cells and promotes the production of relatively
large amount of IgM , Ig E and noncomplement – activating IgG.

The TH 2 subset also support allergic reaction.

Examples of cytokines are :

1)IFN- gamma : activates macrophage stimulate these cells to


increase microbicidal activity up regulate the level of class II
MHC and secrete cytokine such as IL- 2 which induces TH cells
to differentiate into the TH1 subset.
2) TNF – beta and TNF – gamma mediate inflammation
and delayed hypersensitivity

3) IL- 4 promotes a pattern of class switching that


produces IgG that does not activate the complement
pathway.
Cross Regulation
The effect in which cytokines produced by TH1 and TH2 subset
promotes the growth of the subset that produce them and inhibit
the development and activity the opposite subset.

 Tuberculoid leprosy : the immune response is characterized by a


TH1 - type response with delayed type hypersensitivity and
consisting high level of IL-2 , IFN- gamma and TNF – beta

 Lepromatous Leprosy : is a TH2 type immune response with


high level of IL – 4 , IL – 5 and IL- 10.
Cytokine releated Diseases:
I. Bacterial septic shock : developed because bacterial cell
wall endotoxins stimulate macrophages to over provide
IL- 1 and TNF –alpha to level that cause septic shock.

Symptoms: drop in blood pressure, fever, diarrhea, and


widespread blood clotting in various organs.

Lymphoid and Myeloid Cancer: develop due t


overproduction of IL-6

Chages diseases : caused by protozons Trypanosoma cruzi.

This diseases is caused due to immune suppression.


Therapeutic uses of Cytokines

Cytokines releated strategies continue in particulary in


area such as :

inflammation therapy and modification of the response


during organ transplantation,

infectious disease and

allergy.
References

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