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interleukin-1 Ra 400 interleukin-2 receptor (IL2R)
infections are increased in affected children who have inherited
the condition as an autosomal-recessive trait.
interleukin-1 Ra
IL1 receptor antagonist is a soluble protein that interacts
with IL1R leading to prevention of signal transduction and
prevention of inflammation. Counteracts endotoxic shock.
interleukin-1 receptor antagonist (IL1ra)
An IL1 inhibitor that is structurally homologous to IL1 and
is synthesized by mononuclear phagocytes. This biologically
inactive molecule blocks IL1 activity by binding to its
receptor. Plays a central role in acute and chronic inflammation,
both locally and systemically. It is produced primarily
by monocytes and macrophages and is synthesized
as a precursor that is cleaved by IL1β–converting enzyme
(ICE) to mature IL1β plus a prosegment. Some combination
of mature IL1β, IL1β precursor, and the prosegment is
released by cells.
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Cys 105
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interleukin-2 (IL2)
A 15.5-kDa glycoprotein synthesized by CD4 + T helper
lymphocytes; it was formerly called T cell growth factor.
Critical to the body’s natural defense against microbial
infection and discrimination between self and nonself,
IL2 is a member of a cytokine family that includes IL4,
IL7, IL9, IL15, and IL21. It interacts with a specific IL2
receptor α (CD25), IL2 receptor β (CD122), and a common
γ chain (γc) possessed by λ members of this family of
cytokines. IL2 binding activates the Ras/MAPK, JAK/Stat
and PI 3-kinase/Akt signaling molecules. IL2 is synthesized
during an immune response. Antigens binding to the
T cell receptor activate IL2 secretion and expression of
IL2 receptors (IL2Rs). The binding of IL2 to its receptor
activates growth, differentiation, and survival of antigen-
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NH 2
Schematic representation of interleukin-2 (IL-2).
selected cytotoxic T cells through the activation of specific
genes. IL2 is needed for the development of T cell immunologic
memory. It exerts an autocrine effect, acting on the
CD4 + T cells that produce it. Although mainly produced
by CD4 + T cells, a small amount is produced by CD8 + T
cells. Physiologic amounts of IL2 do not have endocrine
effects; it acts on the cells producing it or on those nearby
acting as a paracrine growth factor. The main effects of
IL2 are on lymphocytes. The amount of IL2 that CD4 + T
lymphocytes synthesize is a principal factor in determining
the strength of an immune response. It also facilitates
formation of other cytokines produced by T lymphocytes,
including interferon γ and lymphotoxins. Inadequate
IL2 synthesis can lead to antigen-specific T lymphocyte
anergy. IL2 interacts with T lymphocytes by reacting with
IL2 receptors and also promotes natural killer (NK) cell
growth and potentiates the cytolytic action of NK cells
through generation of lymphokine-activated killer (LAK)
cells. Although NK cells do not have the p55 lower affinity
receptor, they do express the high-affinity p70 receptor and
thus require high IL2 concentrations for their activation.
IL2 is a human B cell growth factor and promotes synthesis
of antibody by these cells. However, it does not induce
isotype switching. IL2 promotes the improved responsiveness
of immature bone marrow cells to other cytokines.
In the thymus, it is also necessary for T cell development
for the maturation of a unique subset of T cells critical to
immunoregulation and called regulatory T cells (T-regs).
T-reg cells leaving the thymus inhibit other T cells from
recognizing and reacting against self antigens that may lead
to autoimmunity. They accomplish this by preventing the
responding cells from synthesizing IL2, which is necessary
to differentiate between self and nonself. Both IL2 and IL15
aid the synthesis of immunoglobulins by B cells and induce
differentiation and proliferation of natural killer cells.
The main difference between IL2 and IL15 is in adaptive
immune responses. Whereas T-regs prevent self reactivity
by T cells, IL15 is requisite for maintaining specific T cell
responses through supporting survival of CD8 + memory T
cells. The IL2 gene is located on chromosome 4 in humans.
Corticosteroids, cyclosporin A, and prostaglandins inhibit
IL2 synthesis and secretions. Proleukin ® is a commercially
available recombinant form of IL2 approved by the FDA
to treat tumors such as malignant melanoma and renal cell
carcinoma. A number of immunosuppressive drugs used in
prevention of organ transplant rejection, such as cyclosporin
and tacrolimus, or corticosteroids used in the treatment of
autoimmune diseases inhibit IL2 synthesis by antigen-activated
T cells. Rapamycin inhibits IL2R signaling.
interleukin-2 receptor (IL2R)
Also known as CD25. IL2R is a structure on the surfaces
of T lymphocytes, natural killer cells, and B lymphocytes
characterized by the presence of a 55-kDa polypeptide (p55)
and a 70-kDa polypeptide (p70) that interact with IL2 molecules
at cell surfaces. The p55 polypeptide chain is referred
to as Tac antigen, an abbreviation for T activation. The
expression of both p55 and p70 permits a cell to bind IL2
securely with a K d of about 10 –8 . p55, the low affinity receptor,
apparently complexes with p70, the high affinity receptor,
to accentuate the affinity of p70 receptor for IL2. This
permits increased binding in cells expressing both receptors.
In addition, lesser quantities of IL2 than would otherwise be