INTERLEUKIN 2
First called T cell growth factor which gives you a pretty good idea of what it does. IL-2 will support long-term proliferaton in cultures of normal mitogen-or antigen-activated T cells, making it possible for the first time to develop clones of normal T cells.
The Th1 cell is the major producer of IL-2. Induction of IL-2 production by Th cells is associated with their activation. Within 24-48 hours of activation by APC, Th1 cells begin to synthesize and secrete IL-2 and to express high affinity receptors for IL-2.
Acts on NK cells and LAK cells (stimulating proliferation and cytotoxicity).
Also acts on B cells, promoting their growth and stimulating limited Immunoglobulin synthesis (IgG2a)
IL-2 is a single polypeptide
15.5kDa
Encoded by a single gene but you do see some post-translational glycosylation differences. Does not appear to influence function but may influence half-life.
IL-2 receptor
Membrane receptor for IL-2 actually consists of three subunits:
alpha subunit
beta subunit
gamma subunit
gamma + beta has intermediate affinity for IL-2
gamma + beta + alpha has high affinity for IL-2
alpha alone has low affinity for IL-2
alpha is only expressed on activated Th cells
gamma is constitutively expressed on most lymphocytes - alpha and beta expression is restricted and markedly enhanced following activation. This way, only antigen-activated CD4+ and CD8+ T cells will express the high affinity receptor.
gamma + beta is the minimum required for signal transduction but with alpha gives = HIGH AFFINITY
NK cells express the gamma and beta subunits constitutively. Activated Th cells express both high-affinity and low-affinity IL-2 R.
Activated B cells (low numbers) express the low affinity and high affinity receptor.
Interleukin 3
also termed: multi CSF
Produced by both Th1 and Th2 cells
IL-3 has the ability to stimulate hematopoietic cells of multiple lineages.
It is secreted by activated Th cells and has a number of effects that contribute to localized inflammatory reactions, including the stimulation of mast cell growth and histamine secretion.
IFN-gamma
Produced by Th1 cells, Tc cells, and NK cells
Produced in response to IL-2
Functions:
Stimulates B cell production of IgG2a while lowering production of IgG3, IgG1, IgG2b, and IgE
Inhibits the proliferation of Th2 cells and causes a decrease in IL-4 synthesis
Inhibits viral replication in uninfected cells
Enhances the activity of macrophages (greatly enhancing their ability to destroy internalized microorganisms and act as antigen presenting cells)
Enhances the activity of NK cells
Positive loop is created-- activated NK cells produce the cytokine which helps to activate other Nk cells.
Lymphotoxin (TNFbeta)
Produced by Th1 cells and by activated CD8+ T cells
Has sequence homology with TNFalpha and is also encoded within Class III MHC.
TNF beta has a cytotoxic effect on tumor cells - induction of apoptosis
TNF beta also enhances the phagocytic activity of macrophages and neutrophils.
Interleukin 4
Has a broad spectrum of reactivity.
Produced by the Th2 subset of Th cells (when activated) - and mast cells
Best studied is its effect on the activation, proliferation, and differentiation of B cells.
IL-4 exerts different effects on B cells at different stages in the cell cycle.
On resting B cells - IL-4 acts as an activating factor - inducing the resting cells to enlarge in size and increase their expression of Class II MHC.
Then it acts as a growth factor, driving the B cell to proliferate.
Finally, IL-4 acts as a differentiation factor by regulating the class switch to IgG1 and then to IgE. "switch-inducing factor"
Also induces proliferation of Th2 cells and thymocytes in particular
Up-regulates Class II MHC expression and increases phagocytic activity of macrophages.
Stimulates the growth of mast cells
Interleukin 5
Produced by Th2 cells and mast cells
Stimulates B cell proliferation and differentiation
Stimulates the class switch to IgA
Acts synergistically with IL-4 to enhance production of IgE
Induces the growth and differentiation of eosinophils
Interleukin 10
Produced by Th2 cells primarily
Target cell is the macrophage
Originally called cytokine synthesis inhibiting factor because of suppressive effect on Th1 cytokine synthesis.
Now clear that IL-10 primarily acts on activated macrophages to suppress their secretion of IL-1, IL-12, TNFalpha . It also down-regulates Class II MHC expression impacting APC activity.
As a consequence, Th1 cell activity and cytokine synthesis is impacted. In particular there is inhibition of the synthesis of IFN gamma and IL-2.
Conversely, IL-10 is a potent stimulator of activated B cells, inducing Class II MHC and promoting growth.
TGFbeta
Produced by T and B lymphocytes, macrophages, platelets, and mast cells.
Plays a central role in embryonic development, tumorigenesis, wound healing, fibrosis, and immunoregulation.
Inhibits immune function in chronic inflammation and promotes healing.
-TGF is a potent INHIBITOR of T and B lymphocyte proliferation
-inhibits respiratory burst activity and cytotoxic activity of macrophages
-inhibits production of IFNgamma
-inhibits IL-2R expression
-inhibits MHC class II expression
-inhibits cytotoxic T cell development
-inhibits Nk cell production
-inhibits TNFalpha production
Stimulates Class Switch to IgA
Stimulates the proliferation of fibroblasts
Chemotactic for monocytes, neutrophils and fibroblasts
Promotes vascular growth
Upregulates production of collagens and fibronectin
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