cytokines and its types-.ppt by taimoor khan

cytokines and its classes by taimoor khan

1. CYTOKINES
Semester 5
th
Taimoor Khan

2. CYTOKINES
• Cytokines are small secreted proteins which mediate and regulate
immunity, inflammation, and hematopoiesis. They are produced in
response to an immune stimulus.
• Cytokine is the general term for a large group of molecules
involved in signaling between cells during immune responses. All
cytokines are proteins, some with sugar molecules attached
(glycoproteines).
• They are synthesized and released by white blood cells and tissue
macrophages.

3. They are proteins, peptides or glycoproteins in nature.
Cytokines stimulate or suppress the functional activity of
lymphocytes, monocytes, neutrophils, fibroblast and endothelial
cells.
They modulate the function of other cell types. Long known to
be involved in cellular immune response, these products have
additional effects that play important roles in both acute and
chronic inflammation.
200 different human cytokines have been identified

4. TERMS AND DEFINITIONS :
Cytokines generated by mononuclear phagocytes are often
called ‘Monokines’ and those by activated lymphocytes are
reffered to as ‘Lymphokines’.
Additionally, both monocytes and macrophages produce
cytokines such as CSF’s, which stimulate the growth of
immature leukocytes in the bone marrow.

5. GENERAL PROPERTIES
Cytokines are produced during immune and inflammatory
responses and secretion of these mediators is transient and
closely regulated.
Cytokines mediate their effects by binding to specific receptors
on target cells and the expression of cytokine receptors can be
regulated by a variety of exogenous and endogenous signals.

6. Cytokines induce their effects in two ways
1.They act on the same cell that produces them (autocrine effect)
e.g: IL-2 produced by activated T cells promotes T- cell growth
2.They affect other cells in their vicinity (paracrine effect)
e.g: cytokines in immune response releases pro-inflammatory
cytokine (e.g IL-1 & TNF-alpha) that act on nearby endothelial
cells to promote inflammation or tissue repair.

7. The main sets of cytokines are
o Interleukins
o Interferons
o Tumour necrosis factors
o Chemokines

8. INTERFERONS (IFNs)
Interferons (IFNs) are proteins made and released by
helper CD4+ T lymphocytes, as well as through monocytes,
macrophages, and endothelial cells in response to the
presence of pathogens — such as viruses, bacteria or
parasites — or tumor cells.
IFNs belong to the large class of glycoproteins known as
cytokines. Although they are named after their ability to
"interfere" with viral replication within host cells

9. They are produced very early in infection and are the first line
of resistance to a great many viruses
These are particularly important in limiting the spread of
certain viral infections. One group of interferons (IFNα and
IFNβ) is produced by cells which have become virally infected

10. Types of interferon
Based on the type of receptor human interferons have been
classified into two major types.
Interferon type I:
All type I IFNs bind to a specific cell surface receptor
complex known as the IFN-α receptor. The type I interferons
present in humans are IFN-α, IFN-β and IFN-ω.
Interferon type II:
In humans this is IFN-γ

11. FUNCTIONS
they activate immune cells, such as natural killer cells and
macrophages

they increase recognition of infection or tumor cells by up-
regulating antigen presentation to T lymphocytes and

they increase the ability of uninfected host cells to resist
new infection by virus. Certain host symptoms, such as
aching muscles and fever, are related to the production of
IFNs during infection.

13. INTERLEUKINS (ILs)
These are a large group of cytokines produced mainly by T cells, although
some are also produced by mononuclear phagocytes (or) by tissue cells.
The interleukins were first described as signals for communication between
white blood cells (leuk- from leukocytes).
Currently, it is well-known that these molecules are produced and used as
signalling molecules in many cells of the body, in addition to immune cells.

14. They have a variety of functions, but most of them are involved in directing
there cells to divide and differentiate
Interleukins represent a broad family of cytokines that are made by
hematopoietic cells and act primarily on leukocytes
There are currently 35 well-known interleukins, however, there are many
more to be found and characterized.

15. TUMOUR NECROSIS FACTORS (TNF)
Tumor necrosis factors (or the TNF-family) refers to a
group of cytokines family that can cause cell death.
TNF acts via the TNF Receptor (TNF-R) and is part of the extrinsic
pathway for triggering apoptosis.
TNF interacts with tumor cells to trigger cytolysis or cell death.

16. Types:
Tumor necrosis factor-alpha (TNF-α) is the most well-
known member of this class, and sometimes referred
to when the term "tumor necrosis factor" is used.
Tumor necrosis factor-beta (TNF-β), also known as
lymphotoxin is a cytokine that is induced by interleukin
10

17. COLONY STIMULATING FACTORS
(CSFs)
Colony-stimulating factors (CSFs) are secreted glycoproteins which
bind to receptor proteins on the surfaces of hemopoietic stem cells
and thereby activate intracellular signaling pathways which can
cause the cells to proliferate and differentiate into a specific kind of
blood cell
These are primarily involved in directing the division and
differentiation of bone marrow stem cells, and the precursors of
blood leucocytes

18. TYPES:
CSF1 - macrophage colony-stimulating factor
CSF2 - Granulocyte macrophage colony-stimulating
factors (also called GM-CSF and sargramostim)
CSF3 - Granulocyte colony-stimulating factors (also
called G-CSF and filgrastim)

19. GROWTH FACTROS (GF)
A growth factor is a naturally occurring substance capable of
stimulating cellular growth, proliferation and cellular
differentiation.
Growth factors typically act as signaling molecules between cells
and they are important for regulating a variety of cellular
processes.
e.g:
Epidermal growth factor (EGF)
Fibroblast growth factor (FGF)
Granulocyte-colony stimulating factor (G-CSF)
Nerve growth factor (NGF)

20. CHEMOKINES:
This large group of chemotactic cytokines direct
movement of cells around the body, from the blood
stream into tissues and to the appropriate location
within each tissue.
Some of the chemokines also activate cells to carry
out particular functions.
Chemokines are cytokines that share the ability to
stimulate leukocyte movement (chemokinesis) and
directed movement (chemotaxis) and are
particularly important in inflammation.

21. CYTOKINE RECEPTORS
Cytokine receptors fall into four families
1) Type I receptors
2) Type II receptors
3) Type III receptors
4) Type IV receptors

22. TYPE I RECEPTORS:
The largest family of cytokine receptors is Type I receptor
superfamily. It is characterized by an extracellular region
of structural homology approximately 200 amino acids
long.
Receptors for cytokines such as IL-2, IL-3, IL-4, IL-5, IL-6,
IL-7, IL-9, IL-12, G-CSF and GM-CSF belong to this family.

23. TYPE II RECEPTORS:
The Type II family of related cytokine receptors can be
considered part of the immunoglobulin superfamily and
contains receptors for all IFN types as well as IL-10 and
M-CSF
TYPE III RECEPTORS:
TNF family cytokines bind to Type III cytokine receptors
which all have multiple cysteine-rich repeats of about 40
amino acids in the extracellular domain.

24. TYPE IV:
Receptors for IL-1α and β are representative of the Type
IV cytokine receptor family.
Regardless of these subtypes, cytokine
receptors have several common characteristics. They
usually consist of two or more subunits, and receptors
for different cytokines may even share common
subunits.

26. MECHANISMS OF CELL ACTIVATION
The binding of a cytokine to its appropriate receptor sets off a
cascade that leads to induction or inhibition of transcription of a
number of cytokine regulated genes.
This occurs via a chain of protein-protein recognition events
leading to binding of diverse trancription factors to DNA .
Cytokines initiate intracellular signals through ligand-induced
aggregation of receptor components.
Cytokine binding can cause hetero or homo-dimerization of
receptors or trimerization depend on particular family.

29. Rheumatoid Arthritis
RA is a chronic systemic inflammatory disorder that may affect
many tissues and organs but principally attacks the joints.
An auto immune reaction in which T cells play the pivotal role is
widely held to be responsible for the chronic destructive nature of
RA.
Once an inflammatory synovitis has been initiated by an
exogenous agent.

30. T- cells, mainly CD4+ memory cells appear within the affected
joints early early in the development of RA
Soon the endothelial cells of synovial capillaries are activated with
the expression of ICAM-1
Leading to further attachment and transmigration of other
inflammatory cells
This sequence is further enhanced by release of IL-1, TNF-α and
IFN-γ
Activated CD4+ cells simultaneously activate monocytes,
macrophages and promote the release of monokines and activated
B cells with antibody production in affected joints

31. TNF- α and have induces resorption of cartilage and bone
bystimulating release of collagenases from synovial cells.
Up regulates expression of adhesion molecules (ICAM-1)
which inhibits synthesis of proteoglycans in cartilage
Stimulates fibroblasts via platelet derived growth factor.

32. MULTIPLE MYELOMA
Multiple myeloma is a plasma cell cancer that originates
in the bone marrow and is characterized by involvement of
the skeleton at multiple sites.
The proliferation and differentiation of myeloma cells seem to be
dependent on several cytokines most notably ‘IL-6’
Serum levels of this cytokine are increased in patients with active
disease.

33. IL-6 seems to be produced by tumorous plasma cells themselves
as well as by fibroblasts and macrophages in the surrounding
stroma.
In addition to causing the growth of myeloma cells, cytokines also
mediate bone destruction by acting as osteoclast activating
factors.
(TNF-β, IL-1, IL-6 and M-CSF)

34. CYTOKINE THERAPY

35. Non specific stimulation or inhibition of particular
components of the immune system may sometimes be of
benefit.
The best results have been obtained with cytokines and among
these interferon-α (IFN- α) is the most widely used mainly for it’s
antiviral properties.
The most striking clinical effect of a cytokine has been that of G-CSF
in restoring bone marrow function after anti cancer therapy.

36. Interferon beta-1a and interferon beta-1b are used to treat
and control multiple sclerosis, an autoimmune disorder.
Interferon therapy is used (in combination with
chemotherapy and radiation) as a treatment for many
cancers. This treatment is most effective for treating
hematological malignancy; leukemia and lymphomas
including hairy cell leukemia, chronic myeloid leukemia,
nodular lymphoma, cutaneous T-cell lymphoma.
Both hepatitis B and hepatitis C are treated with IFN-α, often
in combination with other antiviral drugs

37. Administered intranasally in very low doses, interferon is
extensively used in Eastern Europe and Russia as a
method to prevent and treat viral respiratory diseases such
as cold and flu.
IFN therapy causes immunosuppression, in particular
through neutropenia and can result in some infections
manifesting in unusual ways.
The discovery that the β chemokines RANTES, MIP
(macrophage inflammatory proteins) suppress HIV-1.

38. CYTOKINE INHIBITORS
Cytokine inhibitors can be used for severe or chronic
inflammatory conditions.
Various ways of inhibiting TNF and IL-1 have proved
valuable in rheumatoid arthritis and more controversially in
septic shock and severe malaria.
e.g:
Cyclosporin A; Pentamidine.