MODULE 4 - CYTOKINES

Cytokines

Variety of proteins secreted by cells of the immune system whose function is to regulate the immune response.

Lymphokines

Produced by T cells

Monokines

Produced by monocytes.

Pleiotropy

Ability of one cytokine to act on different cell types.

IL-1, IL-6, IL-12, IL-18, and TNF-a.

macrophage secrete these cytokines.

Pyrogenic effect

Different cytokines that may have similar effect (redundancy)

Synergy

Some cytokines work optimally only when in association with other cytokines.

Antagonism

Some cytokines may prevent or inhibit the action of others

T cell and B cell receptors

Cytokines are produced by antigenic stimuli acting through —

FC receptors

Antigen - antibody complexes acting through Fc receptors.

T cell receptors

Superantigens acting through —

Toll - like receptors

Pathogen - associated molecules such as lipopolysaccharides acting through —

Autocrine

They bind to receptors on the cell that produced them.

Paracrine

They bind to receptors on cells in close proximity to the cell origin

Endocrine

They spread throughout the body thereby affecting cells in distant location from the source of production.

Interleukins

These are cytokines that regulate the interactions between lymphocytes and other leukocytes.

They are numbered sequentially in order of their discovery.

Interferons

These antiviral cytokines are produced in response to virus infection or immune stimulation.

Its name is derived from the fact that they interfere with viral RNA and protein synthesis.

They may also play a role in the maintenance of pregnancy.

Tumor necrotic factors

Cytokines derived from macrophages and T cells.

Can kill tumor cells although this is not their primary function

TNF - a

The key mediator of acute inflammation

Growth factors

Control leukocyte production by regulating stem cell growth.

This ensures that the body is supplied with sufficient cells to defend itself.

Chemokines

A family of cytokines that play an important role in leukocyte circulation and migration, especially in inflammation.

Acts primarily as chemotactic factors and leukocyte activators.

Interleukin - 1

has a role in inflammation.

Has a key role in fever, hematopoiesis, appetite control, bone metabolism, and acquired immunity.

It induces the production of prostaglandin.

macrophage

This is the major source of Interleukin 1

Interleukin 2

Produced by Th1 cells (t helper) and targets T cells, B cells, and NK cells

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.

Triggers the T cell to proliferate and stimulates the proliferation and cytotoxicity of Th1 cells.

Interleukin 3

Derived from activated Th1 and Th2 cells, NK cells, eosinophils and mast cells.

Stimulates the growth and maturation of bone marrow stem cells for eosinophils, neutrophils and monocytes.

It stimulates mast cell and basophil differentiation and activation.

Promotes immunoglobulin secretion by cells.

Interleukin 4

Produced by activated Th2 cells, mast cells and activated basophils.

Acts on B cells, T cells, macrophages, endothelial cells, fibroblasts and mast cells.

Stimulates the growth and differentiation of B cells.

It has a major importance in the development of allergic reactions by inducing B cells to switch to IgE production.m

Interleukin 5

produced by Th2 cells, mast cells and eosinophils.

In mice, it enhances B cell growth

In humans, it controls the eosinophil production by stimulating growth and differentiation of eosinophil precursors in the bone marrow.

Interleukin 6

Produced by activated macrophages but also by T and B cells.

Produced also by muscle cells during exercise.

It promotes IL-2 production and T cell differentiation.

Synergizes with IL - 4 to promote Th2 cell differentiation.

Required for the final maturation of B cells into plasma cells.

Acts as a cofactor with IL -1 in IgM synthesis and with IL - 5 in IgA synthesis.

Interleukin 9

A stem cell growth factor produced only by Th2 cells.

Promotes the growth of helper T cells and mast cells.

It contributes to the development of allergic diseases.

Interleukin 10

It is an immunosuppressive and anti-inflammatory cytokine that regulates inflammation as well as T cell, NK cells and macrophage function.

It is mainly produces by Th2 cells but may also come from activated macrophages.

It inhibits the synthesis of Th1 cytokines.

Other members of IL - 10 family includes: IL-19, IL-20, IL-22, IL-24, IL-26.

Interleukin 11

It is produced by bone marrow stromal cells, epithelial cells and fibroblasts.

It stimulates B cell growth in association with IL-6.

Stimulates megakaryocytes colony formation in association with IL-3 and promotes the production of acute - phase proteins.

Interleukin 12

produced by monocytes, macrophages, dendritic cells, B cells and keratinocytes.

It may be stored performed in macrophages and rapidly released in large quantities on activation.

Promotes Th1 activity by inducing secretion of IL-2 and IFN- y and enhances T and NK cell proliferation and cytotoxicity.

Synergizes with TNF - a in promoting IFN - y production.

Reduces IgE production by suppressing IL - 4 synthesis.

Interleukin 14

Produced by T cells and some malignant B cells.

Inhibits immunoglobulin secretion and selectivity expands some B cell subpopulations.

Interleukin 15

Derived from activated macrophages, dendritic cells, endothelial cells and fibroblast.

Essential for the prolonged survival of memory cells

IL - 16

Produced by CD8+ T cells, eosinophils, dendritic cells, and mast cells as well as non immune cells.

Receptor is CD4, thus regulates CD4+ t cell recruitment and activation.

When binds to T cells it stimulates chemotaxis and cell adhesion.

Since its production by mast cells is stimulates by histamine, IL- 16 attracts eosinophils and plays an important role in the development of allergies.

IL - 17

Induce the production of cytokines by cells and proliferation of T cells and myeloid stem cells

Proinflammatory since it can recruit and activate neutrophils by stimulating T cell chemokine release.

A link between T cell activation and the mobilization of neutrophils via chemokines.