Module 4: Cytokines
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Variety of proteins secreted by cells of the immune system whose function is to regulate the immune responses (e.g. proliferation, differentiation and maturation of nearby cells)
Cytokines
Lymphokines are produced by
T cells
Monokines produced by
Monocytes
They bind to receptors on the cell that produced them
Autocrine
they bind to receptors on cells in close proximity to the cell
Paracrine
they spread throughout the body thereby affecting cells in
distant location from the source of production
Endocrine
Types and groups of cytokines (5)
Interleukins
Interferons
Tumor Necrotic Factors
Growth Factors
Chemokines
Cytokines that regulate the interactions between lymphocytes and other leukocytes
Interleukins
Numbered sequentially in order of their discovery
Interleukins
Antiviral cytokines that are produced in response to virus infection or immune stimulation
Interferons
Name is derived from the fact that they interfere with viral RNA and protein synthesis
Interferons
Many also play a role in the maintenance of pregnancy
Interferons
Cytokines derived from macrophages and T cells
Tumor necrotic factors
Can kill tumor cells although this is not their primary function
Tumor necrotic factors
the key mediator of acute inflammation
TNF-α
Control leukocyte production by regulating stem cell growth
Growth factors
Ensure that the body is supplied with sufficient cells to defend itself
Growth factors
Family of cytokines that play an important role in leukocyte
circulation and migration, especially in inflammation
Chemokines
Act primarily as chemotactic factors and leukocyte activators
Chemokines
Plays a critical role in inflammation but are not restricted to it
IL-1
Key role in fever, hematopoiesis, appetite control, bone metabolism and acquired immunity
IL-1
Major source is macrophage
IL-1
Induces the production of prostaglandin
IL-1
Produced by Th1 cells and targets T cells, B cells and NK cells
IL-2
Activates helper and cytotoxic T cells and NK cells, but in order to be responsive to IL-2, antigen and IL-12 must first activate T cells and induce expression of both IL-2 and its receptor
IL-2
Triggers the T cell to proliferate and stimulates the proliferation and cytotoxicity of Th1 cells
IL-2
Derive from activated Th1 and Th2 cells, NK cells, eosinophils and mast cells
IL-3
Stimulates the growth and maturation of bone marrow stem cells for eosinophils, neutrophils and monocytes
IL-3
Stimulates mast cell and basophil differentiation and activation
IL-3
Activates eosinophils; promotes macrophage cytotoxicity and phagocytosis
IL-3
Promotes immunoglobulin secretion by cells
IL-3
Produced by activated Th2 cells, mast cells and activated basophils
IL-4
Acts on B cells, T cells, macrophages, endothelial cells, fibroblast and mast cells
IL-4
Stimulates the growth and differentiation of B cells
IL-4
Major importance in the development of allergic reactions by inducing B cells to switch to IgE production
IL-4
Enhances the development of cytotoxic T cells from resting T cells and make helper T cells grown in absence of IL-2
IL-4
Its actions are neutralized by IFN-γ
IL-4
Produced by Th2 cells, mast cells and eosinophils
IL-5
In humans, it controls the eosinophil production by stimulating growth and differentiation of eosinophil precursors in the bone marrow
IL-5
In mice, it enhances B cell growth
IL-5
Produced by activated macrophages but also by T and B cells
IL-6
Also produced by muscle cells during exercise
IL-6
Acts on T cells, B cells, hepatocytes and bone marrow stromal cells
IL-6
Promotes IL-2 production and T cell differentiation
IL-6
Synergizes with IL-4 to promote Th2 cell differentiation
IL-6
Required for the final maturation of B cells into plasma cells
IL-6
Acts as cofactor with IL-1 in IgM synthesis and with IL-5 in IgA synthesis
IL-6
A major stimulator of the acute-phase response
IL-6
Produced by bone marrow and thymic stromal cells
IL-7
Regulates the activity of lymphoid stem cells
IL-7
Major role is to control lymphocyte function
IL-7
Necessary for lymphocytes to produce functioning antigen receptors
IL-7
A stem cell growth factor produced only by Th2 cells
IL-9
Promotes the growth of helper T cells and mast cells
IL-9
Contribute to the development of allergic diseases
IL-9
An immunosuppressive and anti-inflammatory cytokine that regulates
inflammation as well as T cell, NK cells and macrophage function
IL-10
Mainly produced by Th2 cells but may also come from activated macrophages
IL-10
Inhibits the synthesis of Th1 cytokines
IL-10
Other members of IL-10 family include: (they have strong antitumor and some proinflammatory properties)
IL-19
IL-20
IL-22
IL-24
IL-26
Produced by bone marrow stromal cells, epithelial cells and fibroblasts
IL-11
Stimulates B cell growth in association with IL-6
IL-11
Also stimulates megakaryocyte colony formation in association with IL-3 and promotes the production of acute-phase proteins
IL-11
Produced by monocytes, macrophages, dendritic cells, B cells and keratinocytes
IL-12
May be stored preformed in macrophages and rapidly released in large quantities on activation
IL-12
Promotes Th1 activity by inducing secretion of IL-2 and IFN-γ and enhances T and NK cell proliferation and cytotoxicity
IL-12
Synergizes with TNF-α in promoting IFN-γ production
IL-12
Reduces IgE production by suppressing IL-4 synthesis
IL-12
Produced by Th2 cells, cytotoxic T cells, mast cells and dendritic cells
IL-13
Has structural and biological characteristics similar to IL-4
IL-13
Required for optimal induction of IgE
IL-13
Enhances macrophage expression of integrins and is a chemoattractant for monocytes
IL-13
Induced giant cell formation by stimulating macrophage fusion
IL-13
Produced by T cells and some malignant B cells
IL-14
Inhibits immunoglobulin secretion and selectively expands some B cell
subpopulations
IL-14
Derived from activated macrophages, dendritic cells, endothelial cells and fibroblasts
IL-15
Essential for the prolonged survival of memory cells
IL-15
Produced by CD8+ T cells, eosinophils, dendritic cells and mast cells as well as nonimmune cells (e.g. fibroblasts)
IL-16
Receptor is CD4, thus regulates CD4+ T cell recruitment and activation
IL-16
When binds to T cells → stimulates chemotaxis and cell adhesion
IL-16
A potent chemoattractant for CD4+ T cells, eosinophils, dendritic cells and macrophages
IL-16
Since its production by mast cells is stimulated by histamine, IL-16 attracts eosinophils and plays an important role in the development of allergies
IL-16
A family of cytokines involved in regulating immune responses
IL-17
Induce the production of cytokines by cells and proliferation of T cells and myeloid stem cells
IL-17
Proinflammatory since it can recruit and activate neutrophils by stimulating T cell chemokine release
IL-17
A link between T cell activation and the mobilization of neutrophils via
chemokines
IL-17
Produced in large quantities by lymphoid dendritic cells and smaller amount by lymphocytes, monocytes and macrophages in response to viral infection
Interferon α
a potent stimulator of both innate and adaptive immunity
Interferon α
activates NK cell-mediated cytotoxicity activity
Interferon α
stimulates the differentiation of monocytes into dendritic cells and maturation and activity of dendritic cells
Interferon α
also participate in the transition from innate to acquired immunity
Interferon α
stimulate memory T cell proliferation, activates naïve T cells and enhances antigen specific T cell priming
Interferon α
also promotes antibody production and alters class switching
Interferon α
Produced by fibroblasts in response to viral infection
Interferon β
Interferes with viral RNA and protein synthesis
Interferon β
Unrelated to other interferons and only named because of its antiviral activity
Interferon-γ
Produced by Th1 cells and some T cells and NK cells
Interferon-γ
Acts on B cells, T cells, NK cells and macrophages
Interferon-γ
Stimulated B cell production and enhances T cell production of MHC class I molecules but not production of MHC class II molecules
Interferon-γ
Inhibits the production of IL-4 by Th2 cells resulting to blocked IgE production in vitro
Interferon-γ
Enhances the activities of NK cells; a potent stimulator of innate immunity
Interferon-γ
Note 
Flashcards (26)