cytokines,attributes,mode of action

2. Cytokines are a group of proteins made by the immune
system that act as chemical messengers.
Different cytokines,
including
chemokines,
interferons,
interleukins,
lymphokines and
tumor necrosis factor

3. Cytokines / immunocytokines (Greek , cyto =‘cell’ & kinos
=‘movement’) are low molecular weight regulatory proteins
or glycoproteins secreted by white blood cells and various
other cells in the body in response to a number of stimuli.
role in cell-to-cell communication
Their major functions are to
mediate and regulate
immune response and
inflammatory reactions.

4. The activity of cytokines was first recognized in the mid-
1960s, when supernatants derived from in vitro cultures of
lymphocytes were found to contain soluble factors.
The advent of hybridoma technology allowed the production of
artificially generated T-cell tumors that constitutively produced IL-
2, allowing for its purification and characterization.
Gene cloning techniques developed during the 1970s and
1980s then made it possible to generate pure cytokines by
expressing the proteins from cloned genes derived from
hybridomas or from normal leukocytes, after transfection into
bacterial or yeast cells.

5. ELISA assays measure the
concentrations of cytokines in
solution.
Elispot assays quantitate
the cytokines secreted by
individual cells.
cytokine-specific antibodies
can be used to identify
cytokine-secreting cells using
intracellular cytokine staining
followed by flow cytometry or
immuno-fluorescence
microscopy

6. How Cytokines Initiate Cell-to-Cell Signaling?
Cytokines act only on cells
bearing specific receptors
Binding
triggering signal-
transduction pathways
alter gene expression in the
target cells.

7. The cytokines and their fully assembled receptors exhibit
very high affinity for each other and deliver intracellular
signals.
The cytokines and their receptors exhibit very high affinity
for each other, with dissociation constants ranging from 10
–10 to 10 –12 M.
Because their
affinities are so
high, cytokines
can mediate
biological effects
at picomolar
concentrations

8. Cytokines Have Numerous Biological Functions
The principal producers are TH cells,dendritic cells, and
macrophages. Cytokines released from these cell types are
capable of activating entire networks of interacting cells.
Among the numerous
physiological
responses that require
cytokine involvement are the
generation of cellular and
humoral immune responses,
the induction of the
inflammatory response, the
regulation of hematopoiesis,
and wound healing.

10. Distance
Autocrine
Endocrine
Blood circulation
Paracrine Nearby
self
Autocrine
Cytokine binds to
receptor on cell that
secreted it.
Paracrine
Cytokine binds to
receptors on near by
cells.
Endocrine
Cytokine binds cells
in distant parts of
the body

11. Pleiotropic- phenomenon of
different actions produced by
same cytokine on different
targets

12. redundancy- different cytokines can have the same
effects on same targets.

13. Synergism - occurs when the combined effect of
two cytokines on cellular activity is greater than the
additive effects of individual cytokines.

14. •Antagonism that is, the
effects of one cytokine inhibit
or offset the effects of another
cytokine.

15. Cascade effect ---
cytokines can stimulate the
production of other cytokines.

16. Cell growth
Cell differentiation
Cell death
Induce non-responsiveness to other cytokines/cells
Induce responsiveness to other cytokines/cells
Induce secretion of other cytokines
Cytokine -mediated effects

17. Depending on the type of cell involved in the production of
cytokines
two major types;
 monokines and
lymphokines.
The former are secreted only by monocytes, while the
later are released by lymphocytes.

18. Cytokines can also be classified as pro-inflammatory and
anti-inflammatory.
.

19. While the pro-inflammatory ones induce inflammation in
response to tissue injury.
The function of anti-inflammatory cytokines {(IL-4), (IL-
10), and (IL-13)} is exactly the opposite.
Their purpose is to lower the inflammatory response

20. Major cytokines include:
Lymphokines
Interleukins (IL)
Monokines
Interferons (IFN)
colony stimulating factors (CSF)
Tumor Necrosis Factors-Alpha
and Beta (TNF)

21. Interleukins - that act as mediators between leukocytes.
The vast majority of these are produced by T-helper cells.
Lymphokines - produced by lymphocytes.
Monokines - produced exclusively by monocytes.
Interferons - involved in antiviral responses.
Colony Stimulating Factors - support the growth of cells
blood cell .
Chemokines - mediate chemoattraction (chemotaxis)
between cells.

23. A small group of cytokines
(IL1a, IL1b and IL18) have a
beta structure characterised by
a typical b-trefoil fold.
A second and larger group
(including TNFa, TNFb, CD40L,
OX40L, Trail and Rankl) also
have a separate and distinctive
beta structure (so called jelly
roll fold) characterised by a non
covalent, trimeric assembly
The largest family of non-chemokine cytokines have a alpha
structure (so called four-helical fold) and exhibit wide
variations of this fold.

25. Cytokine Receptors Fall Within Five Families
Receptors for the various cytokines are quite diverse structurally,
but almost all belong to one of five families of receptor proteins:

26. The first four receptor families include single-pass
transmembrane proteins whose extracellular moieties have
complex multidomain structures and are all beta proteins
The first family comprises proteins whose ecto domain contains
Ig-type domains, the second one members of the TNF receptor
family, proteins that, like-their ligands, these receptor assemble in
homotrimeric structures.

27. the chemokine receptors have a structure different from that of
all other cytokine receptors. These proteins are seven-pass
transmebrane proteins and work as classic G-protein coupled
receptors

28. Diagram showing comparative structural features of cytokine receptors of different
families.

29. Cytokine signaling mechanisms
A number of cytokine receptors signal via the JAK/STAT
pathway.
These include the receptors for IL2, IL-3, IL-4, IL-6, IL-10, IL-12
and IFN-γ γγ γ.Cytokine receptor subunits are associated with
JAK kinases.

30. 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 cell’s DNA
Transcription of specific target genes

31. 1.- Binding of cytokine
causes dimerization of
receptors and activation
of JAK kinases.
2.- Activated JAK kinases
phosphorylate receptor
sites and create docking
sites for STAT molecules.
JAK = Janus Kinase - OR -
Just Another Kinase
STAT = Signal
Transducers and Activators
of Transcription

33. Biological functions of cytokines
1.Take part
in
nonspecific
immunity
2. Take part
in specific
immunity
3. Stimulate
hematopoie
sis
4. Take part
in
inflammator
y reaction

34. Immunology by Kuby
http://pathmicro.med.sc.edu/mobile/m.immuno-
13.htm
http://www.rndsystems.com/research_topic.aspx?r=
14
http://www.ebioscience.com/resources/pathways/cy
tokine-network.htm
http://www.prospecbio.com/Cytokines
http://www.sinobiological.com/What-Is-Cytokine-Cytokine-
Definition-a-5796.html