3. INTRODUCTION
• CYTOKINES: 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
• They mediate and regulate immunity,inflammation and
haematopiosis
• Involved in signalling between cells during immune response
• All cytokines are proteins ,some with sugar molecules attatched
(glycoproteins)
4. • Cytokines generated by mononuclear phagocytes are often called
‘monokines’ and those by activated lymphocytes are referred to as
‘lymphokines’
• Additionaly 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 response
and secretions of these mediators is transient and closely
regulated
• Cytokines effect are often redundant and these proteins can
influence the synthesis or action of other cytokines
• Cytokines bind to specific receptors on the membrane of target
cells ,triggering signal transduction pathways that ultimately alter
gene expression in target cells
• Cytokines and their fully assembled exhibit high affinity for each
other and deliver intracellular signals
6. • A cytokine may bind to receptors on the membrane of the same
cell that secreted it exerting AUTOCRINE EFFECT for eg:IL2
produced by activated T cells promote T cells growth
• A cytokine may bind to the receptors on the target cell in close
proximity to the producer cell exerting PARACRINE EFFECT for eg:
IL7 produced by bone marrow stromal cells promotes the
differentiation of B-cell progenitors in marrow
• In few cases it may bind to target cells in distant parts of the body
exerting ENDOCRINE EFFECT for eg: insulin is secreted by pancreas
and regulate the storage and use of carbohydrate in whole body
9. Other
• Type 1 & type 2
• Mediators of natural immunity
• Mediators of adaptive immunity
10. INTERLEUKINS(Ils)
• These are produced mainly by T cells ,although some are also
produced by mononuclear phagocytes or by tissue cells
• These were first described as signals between WBC
• Currently these molecules are produced and used as signalling
molecules in many cells of the body,in addition to immune cells
• They have a variety of functions but most of them are involved in
directing there cells to divide and differentiate
11. INTERFERONS
• 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
• They are named after their ability to interfere with viral
replication within host cells
• They play an important role in the first line of defense against
viral infections
• They are induced at an early stage of viral infection before the
specific immune system has had time to respond
12. TYPES OF INTERFERONS
• Interferons type 1 : all type 1 IFNs bind to a specific cell surface
receptor complex known as the IFN –alpha receptor.the type 1
receptor present in humans are – IFN-alpha,IFN-BETA and IFN-
omega
• Interferons type 2: in humans this is IFN-gamma
13.
14. GROWTH FACTORS
• These are naturally occurring substance capable of stimulating
cellular growth ,proliferation and cellular differentiation
• These typically act as signalling molecules between cells and they
are important for regulating a variety of cellular processes
• For eg: epidermal growth factors(EGF)
• fibroblast growth factors (FGF)
• granulocyte colony stimulating factors(G-CSF)
• nerve growth factors(NGF)
15. CHEMOKINES
• This group direct movement of cells around the body from the
blood stream into tissues and to the appropriate location within
each tissue
• Some chemokines also activate cells to carry out particular
functions
• They share the ability to stimulate leukocyte
movement(chemokinesis)and directed movement (chemotaxis) and
are particularly important in inflammation
16. Tumor necrosis factors(TNF)
• TNF refers to a group of family that can cause cell death
• TNF acts via TNF receptor and is a part of extrinsic pathway for
triggering apoptosis
17. Types of TNF
• TNF-alpha: it is the most well known member of this class and
sometimes referred to when the term TNF is used
• TNF- beta: also known as lymphotoxin is a cytokine that is induced
by interleukin 10
18. COLONY STIMULATING FACTOR (CSFs)
• These are secreted glycoproteins which bind to receptor proteins
on the surface of hematopoitic stem cells and thereby activate
intracellular signalling 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
21. Type 1 receptors
• These are characterized by extracellular region of structural
homology approx. 200 amino acids long
• Receptors for cytokines such as IL-2,IL-3,IL4,IL-5,IL-6,IL-7,IL-9,IL-
12,G-CSF AND GM-CSF BELONG TO THIS FAMILY
22. TYPE 2 RECEPTOR
• The type 2 family of related cytokine receptors can be considered
part of immunoglobin superfamily and contains receptors for all
IFN types as well as IL- 10 and M-CSF
23. Type 3 receptor
• TNF family cytokines bind to type 3 cytokine receptors which all
have multiple cysteine-rich repeats of about 40 amino acids in the
extracellular domain
24. Type 4 receptor
• Receptors of IL-1 alpha and beta are representative of the type 4
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
