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cytokines notes

MBT309 Basic Immunology of Aquatic Animals
Concept & Characteristics
Cytokines are collection of polypeptides used for communications between cells
o Small proteins are secreted by cells and exert their biological activity through specific cell
surface receptors
Play role similar to hormones (messengers of the endocrine system)
o Hormones usually act at a distance
o Cytokines act locally
Play an important role in both innate & adaptive immunity
o Old: monokine, lymphokine
o New: colony stimulating factor, interleukin, interferon, tumor necrosis factor, growth factor,
General properties of cytokines:
o Small proteins (MW: ~ 15-30 KD)
o Extremely potent
o The production is transient (lasting only for a short time) & tightly regulated
o Autocrine, paracrine or endocrine
 autocrine signaling acts on the signaling cell
 paracrine signaling acts on nearby cells
 endocrine signaling uses the circulatory system to transport ligands
o Non-specific & non-MHC restriction
Produced by cells as part of normal cellular activity or the result of environmental trigger
Bind to receptors on cells
Trigger signal transduction pathways
Initiate synthesis of new proteins
How to regulate cytokines response:
o Only cells expressing receptors for specific cytokines can be activated by them
o Many cytokines have very short half-lives, only cells in close proximity will be activated
o High concentrations of cytokines are needed for activation, only cells in close proximity will
be activated, may require cell-to-cell contact
Action of cytokines:
a) Pleiotropy
 Affects multiple cell types
 IFN-α/β
b) Cascading
 Cytokines acting sequentially
c) Redundancy
 >1 cytokine have the same action
 IFN-α/β & IFN-γ
d) Synergy
 ≥2 cytokines cooperate to produce an effect that is different or greater
than the combined effect of the 2 cytokines when functioning
 IL-12 & IL-18
e) Antagonism
 ≥2 cytokines work against each other
 IL-4 & IL-12
MBT309 Basic Immunology of Aquatic Animals
There are many cytokines with multiple functions & apparent redundancy of action forming a
complex communication network
Cytokines that mediate innate immunity:
o Interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), interferons & IL-6
Cytokines that regulate lymphocyte growth, activation & differentiation
o IL-2, IL-4, IL-5, IL-12, IL-15 & transforming growth factor-β (TGF-β)
Categories of cytokines:
1) Interleukin (IL)
2) Interferon (IFN)
3) Tumor necrosis factor (TNF)
4) Colony stimulating factor (CSF)
5) Chemokine
6) Growth factor (GF)
(1) interleukin
o Not stored inside cells
o Quickly synthesized & secreted in response to infection
o Key modulators of behaviour of immune cells
o Mostly secreted by T-lymphocytes & macrophages
o IL 1 ~ 33
 IL-2: T cell growth factor
 IL-4: B cell growth factor, Th2 type)
 IL-6: Th2 type
MBT309 Basic Immunology of Aquatic Animals
IL-8: belongs to chemokine
IL-10: Th2 type
IL-11: stimulator of platelet
IL-12: Th2 type
What do interleukins do?
 Proliferation of immune cells
 Inflammation
 Increase antibody production
 Activation of immune cells
IL-4 & 5
IL-10 & IL-12
Protein produced by macrophages
Activates T & B cells, neutrophils, epithelial cells & fibroblasts
Activates T cells to produce IL-2
It is and endogenous (originating from within) pyrogen
 Low-molecular-weight protein released from phagocytic leukocytes in response to
several substances of diverse nature
A protein produced by helper T cells
Stimulates both helper and cytotoxic T cells
Acts through the induction of a specific receptor (IL-2 receptor) on the cell surface
Reacts in combination with IL-4 to stimulate growth of B cells
Proteins produced by helper T cells
Promote growth & differentiation of B cells
 IL-4 enhances humoral immunity by increasing number of Th-2 cells
 IL-4 is required for class switching of Igs & enhances IgE production
 IL-5 increases IgA production & helps in activation of eosinophils – defense against
helminths (large macroparasites – worms)
Produced by helper T cells & macrophages
Stimulates B cells to differentiate
Induces fever by acting on hypothalamus
Regulate the production of Th-1 cells
IL-12 is produced by macrophages and promotes the development of Th-1 cells
IL-10 is produced by Th2 cells & inhibits the development of Th-1 by limiting the
production of IFγ
MBT309 Basic Immunology of Aquatic Animals
The relative amounts of IL-4, IL-10 & IL-12 drive the differentiation of Th-1 & Th-2 cells and
enhance either cell mediated or humoral immunity respectively.
(2) Interferon (IFN)
o Signalling proteins produced by virus infected monocytes & lymphocytes
o Secreted proteins – key anti-viral proteins
 Interfere with virus replication
 Warn the neighbouring cells that a virus is around
 If we did not have IFNs – die of influenza virus infection
o IFNs mediators of the innate immune response & Th1/CTL (Cytotoxic T lymphocytes)
o Groups of IFNs
 Type I IFN: IFN-α & IFN-β
 The major source is leukocyte, fibroblasts & virus infected cells
Induce resistance to viral replication in all cells, increase MHC class I
expression and antigen presentation in all cells, activate NK cells to kill
virus-infected cells
Type II IFN: IFN-γ
 Mainly produced by activated T cells & NK cells
 Macrophage activation, increase microbicidal activity, development of th1 cells,
increased MHC expression, antigen presentation, isotype switching to
opsonizing and complement-fixing antibodies
 Promoting tumor immunoevasion.
Enhances the expression of Class I & II MHC
 MHC: The major histocompatibility complex (MHC) is a set of genes that code for cell
surface proteins essential for the acquired immune system to recognize foreign
 main function: to bind to antigens derived from pathogens and display them on the cell
surface for recognition by the appropriate T-cells.
Production of Type I IFNs by infected cells
 Type I IFNs are transcriptionally regulated & are induced following recognition of
pathogen components during infection by various host pattern recognition receptors.
 3 main pathways leading to the production of type I IFN
 The RIG-I pathway is activated upon infection by RNA viruses
 The adaptor protein TRIF which is recruited by TLR3 & TLR4
 The TLR7/8 & TLR0 leading to the activation of the transcription factor IRF7
Cytokine receptor
Time scale of cytokines production
Biologic activity
MBT309 Basic Immunology of Aquatic Animals
Hijack the Immune System