Cytokines:

Properties and
receptors
 Cytokines
Cytokine: Any low-molecular-weight
regulatory protein or glycoprotein (normally
less than 30Kd) secreted by immune cells or
other cells of the body in response to an
stimuli.
Cytokines through interaction with specific
cell-surface receptors, regulate the
development or function of another cell. (to define
their role in cell-to-cell communication)
Cytokines
The term cytokine encompasses those cytokines
secreted by lymphocytes (lymphokines) and those
secreted by monocytes and macrophages
(monokines).
Many cytokines are referred to as interleukins (IL) as
they are secreted by some leukocytes and act upon
other leukocytes.
Chemokines: A subgroup of cytokines that affect
chemotaxis and other aspects of leukocyte behavior.
They play important role in nflammation.
Properties of cytokines
Cytokines bind to specific
receptors on the target cells and
trigger signal transduction
pathways which induce the
changes in gene expression.
In general, cytokines and their
receptors have very high affinity to
each other with issociation
constants ranging from 10-10 to
10-12 M.
Thus, cytokines can mediate
biological effect at picomolar
concentrations.
Properties of cytokines
Cytokines may have
autocrine function (when
secreted, will react with the
cell from which they came, e.g.
IL-2)
Cytokines may have a in close
proximity to the producer cell
when secreted) or an
endocrine function (act on
distant cells). IL-2
Cytokines always interact with
ther cells via specific cell
surface receptors
Cytokine effects
Cytokines exhibit the attributes of
pleiotropy, redundancy, synergy,
antagonisms, & cascade induction
which allow them to regulate cellular
activity in a coordinated, interactive
manner.
Pleiotropy: A cytokine which has
different biological effects on different
target cells is considered having
pleiotropic effects.
Redundancy : Two or more cytokines
that share a similar effect/function are
said to be redundant. This is
particularly true of

chemokines.
Cytokine Effects
Additive - the effect of 2
cytokines given together
equals the sum of each
individual effect
Synergistic - the effect of 2
cytokines given together
exceeds the additive effect
of each individual effect.
Antagonistic - the effect of a
2nd cytokine nullifies or
reverses the effect of the
1st.
Cascade Induction

Certain important cytokines induce

a pyramid of effects, inducing a
cascade of cytokine secretion.
In this, action of one cytokine on a
target cell induces that cell to
produce one or more cytokine which
in turn may induce other target cells
Cytokine families
Cytokines belong to four families
The hematopoietin family
The interferon family
The chemokine family or
The tumor necrosis factor family.
Cytokine functions
More than 200 proteins with cytokine activity have been
described.
Cytokines performs numerous biological functions such as
Development of cellular and humoral responses
Induction of the inflammatory responses
Regulation of hematopoiesis
Control of cellular proliferation and differentiation
Healing of wounds
Cytokines act in a antigen-nonspecific manner.
Cytokines effect any cells which bear the appropriate
receptors and are in a physiological state to respond to
cytokines.
Regulation of cytokine function
There are mainly three factors which keep the
non-specific cytokines from activating cells in a
non-specific fashion during the immune
response.
Receptor expression by target cells only
after antigen activation
Requirement for direct interaction between
the cytokine producing cells and the target
cell ensures that effective concentration
gradients are present only within the local
microenvironment.
Short half-lives of most cytokines in bodily
fluids
IL-1 : activates Antigen presenting cell and CD4+ lymphocytes; affect the differentiation
of the B-Cells and T-Cells and other immunocompetent cells and takes part in the
regulation of productions of other cytokines and GM-CSF (Granulocyte-
Macrophage Colony-Stimulating Factor)
IL-2 : stimulates the proliferation and activation of B-Cells and T-Cells
IL-3 : is a poly potent activator of the hemopoietic cells. It stimulates NK-Cells and acts
as a synergist with IL-4 during the induction of CD4+ lymphocyte activation
process
IL-4 : plays a role in the differentiation of TH2 (T Helper Type-2), in allergic responses,
and in the switching of antibody types
IL-5 : stimulates the production and maturation of eosinophils during inflammation
IL-8 : acts as a chemotactic factor that attracts neutrophils, basophils and T-Cells to
sites of inflammation
IL-10 : acts to repress secretion of pro-inflammatory cytokines

IL-12 : is a critical linker between the innate immunity and adaptive immunity, capable of
TH1 (T Helper Type-1) differentiation and IFN-Gamma release by T-Cells and
NK cells
 Cytokine Receptor Families
Cytokines must bind to specific receptors in order to exert its
biological effect.
Five families of receptors exist
1. Ig superfamily receptors
2. Hematopoietin receptor family (class I cytokine receptor family)
3. Interferon receptor family (class II cytokine receptor family)
4. TNF receptor family
5. Chemokine receptor family
In general (especially class I and Class II receptor families), cytokine
receptors consist of multiple domains or multiple subunits.
In multiple subunits, one attributes the specificity of the receptor for
its ligand, & the other is responsible for signal transduction.
Structure of Receptors
Cytokine receptors initiate signaling upon
binding to cytokines.
Certain cytokine receptors may share a
common signal-transducing subunit (most
common in Hematopoietin family receptors).
Based on this, several subfamilies of
Hematopoietin family receptors (class I
receptors) have been identified and each
subfamily has an identical signal-transducing
subunit.
This common subunit may account for the
similar functions of different cytokines
Subfamilies of Class I cytokine
receptors
Defects in gamma chain of IL-2
receptor subfamily result in
congenital X-linked severe
combined immunodeficiency
(XSCID) due to loss of all the
cytokine functions mediated by
IL-2 receptor subfamily.
 Ligasi APC ( Sel dendritik) dan
polarisasi Thelper (Th1, Th2 Treg)
 Ligasi APC ( Sel dendritik) dan
polarisasi Thelper (Th1, Th2 Treg)

PAMP : Pathogen Associated Moleculer

Pattern
PRR : Pattern Recognittion Receptor
Pathway Anti inflamasi IL10
Terimakasih
 Asep= Teknisi
Nuzul= Teknisi
Nur Halim= Teknisi
Seno - Sekuriti