Presentation on cytokines. kuby's book of immunology 6th edition

1. CYTOKINES
Presented by: Urooj Jarral
Mphil Scholar
Mirpur University Of Science And
Technology

2. Contents
• Introduction
• Properties of cytokines
• Types of action
• Attributes
• Discovery
• Structure
• Cytokine families
• Biological functions of cytokines
• Non-specificity of cytokines
• Cytokine receptor
• Subfamily of class 1 receptor
• JAK/STAT pathway
• Cytokine antagonists

3. Cytokines
• Molecules that communicate among cells of the
immune system are referred to as cytokines.
• Low molecular weight proteins (30kD).
• Binds receptor, alter gene expression.
• Cytokines regulate immune responses.
• Can activate many cells.
• Cytokines released by T h cells can affect B-cells,
NK cells, macrophages, CTLs.

4. • Cytokine secreted by lymphocytes- lymphokines.
• Cytokines secreted by monocytes and
macrophages- monokines.
• Interleukins: they are secreted by some
leukocytes and act on other leukocytes. IL1-IL29.
• Chemokines: a group of low molecular weight
cytokines that affect chemotaxis and other aspect
of leukocyte behaviour.

5. Properties of Cytokines
• Cytokines bind to
specific receptors
on the membrane
of target cells,
triggering signal
transduction
pathway that
ultimately alter
gene expression in
target cell.

6. Cytokines: Types of Action
• Autocrine – A condition
in which the cell acted on
by a cytokine is the
source of the cytokine.
• Paracrine – Regulatory
secretions that arrive by
diffusion from a nearby
cellular source.
• Endocrine – Regulatory
secretions that pass from
the producer cell to
target cell by via the
bloodstream.

7. Cytokine Attributes
• Pleiotropy – a given cytokine has different
biological effects on different target cells.
• Redundancy – When two or more cytokines the
mediate similar functions
• Synergy - When the combined effect of two
cytokines on cellular activity is greater than the
effects of the individual cytokine.
• Antagonism – the effects of one cytokine inhibit
or offset the effects of another cytokine.

10. • Cascade Induction –
when the action of
one cytokine on a
target cell induces
that cell to produce
one or more other
cytokines, which in
turn may induce other
target cells to produce
other cytokines.

11. Difference btw cytokines, hormones
and growth factors
• They differ in their modes of expression.
• Growth factors are produced constitutively,
cytokines and hormones are produced in
response to stimuli.
• Hormones act in long range; endocrine
fashion whereas cytokines act over short
distance in autocrine or paracrine fashion.
• Hormones are produced by specialized glands;
cytokines are produced by vaiety of cell.

12. Discovery
• The activity of cytokines was first recognized in the
mid1960s, when supernatants derived from in vitro
cultures of lymphocytes were found to contain soluble
factors, usually proteins or glycoproteins, that could
regulate proliferation, differentiation, and maturation
of immune system cells.
• Production of these factors by cultured lymphocytes
was induced by activation with antigens.
• However, biochemical isolation and purification of
cytokines was initially hampered because of their low
concentrations in the culture supernatants and the
absence of well-defined assay systems for individual
cytokines

13. • 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.
• Since then, monoclonal antibodies specific for many
cytokines have made it possible to develop rapid,
quantitative, cytokine-specific immunoassays
• 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.

14. Structure

15. Cytokines belong to four families
• The hematopoietin family
• The interferon family
• The chemokine family
• The tumor necrosis factor family.

16. Cytokines have numerous biological
functions
• Principle producers are-T helper, dendritic and
macrophages.
• Among numerous physiological responses that require
cytokine involvement are
 Development of cellular and humoral immune
responses
 Induction of inflammatory response
 Regulation of hematopoiesis
 Control of cellular proliferation Differentiation
 Healing of wounds
• Cytokines act in antigen-non specific manner.

17. Non-specificity of cytokines and
specificity of immune system
• Cytokine receptors are often expressed on a cell
only after that cell has interacted with antigen. In
this way, cytokine activation is limited to Ag-
activated lymphocytes.
• Cytokines secreted at the junction of these
interacting cells reach high enough local
concentrations to affect the interacting cells, but
not more distant cells.
• The half-life of cytokines is usually very short,
ensuring that they act for only a limited period of
time and thus over a short distance.

20. Cytokine Receptors
Cytokine receptor fall within 5 families
• Immunoglobulin superfamily receptors
• Class 1 cytokine receptor family
(hematopoietin family)
• Class 2 cytokine receptor family (interferon
receptor family)
• TNF family
• Chemokine receptor family

21. Immunoglobulin superfamily
receptors
• This superfamily Includes
the receptor for IL-1.
• Two forms of IL-1 called IL-
1alpha and IL-1 beta.
• Two different receptors for
IL-1 are known. Type 1 IL-
1R and type 2 IL-1R.
• IL-1 plays role in
inflammation and
designated as
proinflammatory cytokine.

22. Class I cytokine receptor family
• Member of this family
have conserved a.a
sequence in the
extracellular domain
consisting of 4
cysteine residues and
conserved sequence
of tryptophan-serine-
any a.a-tryptophan
serine (WSXWS)

23. Class II cytokine receptor family
• Possess the conserved
CCCC motif but lack
WSXWS motif present
in class 1 cytokine
receptor.

24. TNF and Chemokine receptor

25. Subfamilies of class I cytokine
receptor have signaling subunits in
common.
Three subfamilies of class I cytokine receptor
• GM-CSF receptor subfamily (common Beta
subunit)
• IL-6 receptor subfamily (common gp130
subunit)
• IL-2 receptor subfamily (common gamma
subunit)

26. GM-CSF receptor subfamily

27. Interaction between cytokine-specific
subunits and common signal
transducing subunits of cytokine
receptor

29. IL-6 receptor subfamily

30. IL-2 receptor subfamily

31. Signal transduction mediated by class I
and class II receptors( JAK/STAT
pathway)

33. JAK and STAT combinations
• Lymphocyte
development (JAK 3)
• IFN gamma signaling
(JAK 1)
• NK cell activation
(STAT 4)
• WBC formation (STAT
5)

34. Cytokine antagonists
1. Number of proteins can inhibit cytokine
activity
• Can bind to receptor, fail to activate the cell, OR
• Can bind directly to cytokine, inhibiting it
2. Viruses have developed strategies
• Cytokine homologs
• Soluble cytokine binding proteins
• Homologs of cytokine receptors
• Interference with intracellular signaling
• Interference with cytokine secretion
• Induction of cytokine inhibitors in the host cell

35. • Best characterized inhibitor is the IL-1Ra which binds to
IL-1 receptor but has no activity.
• Binding of IL-1Ra to IL-1R blocks binding of both IL-
1alpha and IL-1 beta, thus accounting for its
antagonistic properties.
• Epstein-Barr virus (EBV) produces an IL-10-like
molecule that binds to the IL-10 receptor and like
cellular IL-10, suppresses Tн 1-type cell-mediated
responses which are effective against many
intracellular parasites such as viruses.
• Molecules produced by viruses that mimic cytokines
allow the virus to manipulate the immune response in
ways that aid the survival of the pathogen.

36. References
• Chap 12 kuby’s immunology 6th edition.