CYTOKINES

Sanarto Santoso
Faculty of Medicine
Brawijaya Unversity

Introduction

Cytokines are protein secreted by the

cells of innate and adaptive immunity that
mediate many of the functions of these
cells

Cytokines are produced in response to

microbes and other antigens, and
different cytokines stimulate diverse
responses of cells involved in immunity
and inflammation

The Nomenclature of
Cytokines

Often based on their cellular sources

Monokines produced by mononuclear
phagocytes
Lymphokines produced by lymphocytes
Cytokines generic term is the prefered
name for this class of mediators
Interleukins because many cytokines are
made by leucocytes and act on other leucocytes
Chemokines (chemotactic cytokine) stimulate
leucocyte movement and regulate the migration
of leucocytes from the blood to tissues

General Properties of
Cytokines
Secretion is a brief, self limited event
The actions are often pleiotropic and
redundant
Often influence the synthesis and actions of
other cytokines
Their actions may be local and systemic :
- autocrine action
- paracrine action
- endocrine action
Initiate their actions by binding to specific
membrane receptors on target cells

General Properties of Cytokines

General Properties of Cytokines

General Properties of
Cytokines

The cellular responses to most

cytokines consist of changes in gene
expression in target cells, resulting in
the expression of new function and
sometimes in the proliferation of the
target cells

Functional Categories of
Cytokines
1.

Mediators and regulators of innate

immunity

2.

Mediators and regulators of adaptive

immunity

3.

Stimulator of hematopoiesis

Functions of Selected Cytokines

in Host Defense

Comparative Features of the Cytokines of

Innate and Adaptive Immunity

Cytokine Receptors
1.

2.
3.
4.
5.

Type I cytokine receptors

(hemopoietin receptors)
Type II cytokine receptors
IL-1 family receptors
TNF receptors
Seven-transmembrane -helical
receptors (serpentine receptors)

Cytokine Receptors

Cytokines That Mediate and Regulate Innate immunity

Interleukin-1 (IL-1)
The principal function, similar to that of
TNF mediator of the host inflammatory
response to infections and other stimuli
Work together with TNF in innate
immunity and inflamation
The major cellular source macrophage
Induced by bacterial product : LPS, and
by other cytokines such as TNF

Chemokines
Two major family : CC chemokines,
and CXC family
Involved in inflammatory reactions
Leucocyte chemoattractants
Produced by : leucocytes, endothelial
cells, epithelial cells, and fibroblasts
Induced by : microbes, TNF, IL-1

Interleukin-10 (IL-10)
Is an inhibitor of activated macrophage and
dendritic cells control of innate immune
reactions and cell-mediated immunity
Inhibits the production of IL-12, expression of
costimulator and class II MHC molecules
Produced by macrophage and regulatory T cells
Other Cytokines :
IL-6, IL-15, IL-18, IL-23 and IL-27

Role of Cytokines in Innate Immunity

to Microbes

Cytokines of Adaptive
Immunity

Mediate the proliferation and

differentiation of lymphocytes after
antigen recognition in the activation
phase

Mediate the activation of specialized

effector cells in the effector phase

Cytokines of Adaptive Immunity

Interleukin-5 (IL-5)
Activate mature eosinophils and stimulate
the growth and differentiation of
eosinophils
Activated eosinophils are able to kill
helminths
Also stimulate the proliferation of B cells
and production of IgA antibodies
Produced by TH2 subset of CD4+T cells
and by activated mast cells

Interferon- (IFN-)
The principal macrophage-activating
cytokine
Produced by NK cells, CD4 TH1 cells and
CD8 T cells
Signature cytokine of the CD4 TH1 cells

Function in innate and adaptive immunity

Transforming Growth Factor- (TGF-)

Inhibits the proliferation and effector function of T
cells and activation of macrophage inhibit
immune and inflammatory response
Can block development of TH1 and TH2 subsets of
CD4+T cells
Stimulates production of IgA antibodies by
inducing B cells to switch to this isotype
Other Cytokines :
Lymphotoxin (LT)=(TNF-); IL-17; IL-21

Hematopoietic Cytokines