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ZAP-70
A T cell cytoplasmic tyrosine kinase that constitutes part of
the T cell receptor signal transduction pathway.
ZAP-70 (ζ-associated protein of 70 kDa) deficiency
A rare autosomal-recessive type of severe combined immunodeficiency
syndrome (SCID) that features a selective
absence of CD8 + T cells and abundant CD4 + T lymphocytes
in the peripheral blood that do not respond to T cell receptor
(TCR)-mediated stimuli in vitro. Peripheral T cells from
patients manifest defective T cell signaling attributable to
inherited mutations within the kinase domain of the TCRassociated
protein tyrosine kinase (PTK) ZAP-70. ZAP-70
deficiency shows that PTKs, and especially ZAP-70, are
necessary for the physiologic development and function
of T cells in humans. The condition is marked by CD8
lymphocytopenia but presents during infancy with severe,
recurrent, frequently fatal infections resembling those in
SCID patients. Patients have normal or elevated numbers
of circulating CD3 + /CD4 + T lymphocytes but essentially
no CD8 + T cells. The T cells fail to respond to mitogens or
to allogeneic cells in vitro or to form cytotoxic T lymphocytes.
By contrast, natural killer (NK) activity is normal,
and they have normal or elevated numbers of B cells and
low to elevated serum immunoglobulin concentrations. The
thymus may have normal architecture with normal numbers
of double-positive (CD4 + /CD8 + ) thymocytes but no CD8
single-positive thymocytes. The condition results from
mutations in the gene encoding ZAP-70, a non-src PTK
important in T cell signaling.
Z cell
See XYZ cell theory.
(zeta) associated protein of 70 kDa (ZAP-70)
A 70-kDa tyrosine kinase present in the cytosol and
believed to participate in maintaining T lymphocyte receptor
signaling. It belongs to the src family of cytoplasmic
protein tyrosine kinases and is requisite for early signaling
in antigen-induced T lymphocyte activation. It binds to
cytoplasmic tail phosphorylated tyrosines of the ζ chain of
the T cell receptor complex. This is followed by phosphorylation
of adapter proteins that recruit other signaling
cascade components. It is similar to syk in B lymphocytes.
Refer also to lck, fyn, and ZAP (phosphotyrosine kinases in
T cells).
(zeta) chain
A T cell receptor complex expressed as a transmembrane
protein in T lymphocytes that contains immunoreceptor
tyrosine-based activation motifs (ITAMs) in its cytoplasmic
tail and binds ZAP-70 protein tyrosine kinase during T
lymphocyte activation.
(zeta) potential
The collective negative charge on erythrocyte surfaces that
causes them to repulse one another in cationic medium.
Some cations are red cell surface-bound; others are free
Z
RBC
Surface of
shear
Ionic cloud
Zeta potential
The ζ (zeta) potential surrounding red blood cells.
in the medium. The boundary of shear is between the two
cation planes, where the ζ potential may be determined as
negative millivolts (–mV). IgM antibodies have optimal ζ
potentials of –22 to –17 mV, and IgG antibodies have optimum
levels of –11 to –4.5 mV. The fewer the absolute millivolts,
the less the space between cells in suspension. The
addition of certain proteins such as albumin to the medium
diminishes the ζ potential.
Ziagen ®
A carbocyclic synthetic nucleoside analog approved by the
FDA for the treatment of human immunodeficiency virus
(HIV). The mechanism of action includes activation of abacavir
to carbovir triphosphate, which inhibits the activity of
HIV-1 reverse transcriptase by competing with the natural
substrate deoxyguanosine triphosphate (dGTP) and its incorporation
into viral DNA. Abacavir is the active component.
zidovudine (3′-azido-3′-deoxythymidine, AZT)
A reverse transcriptase inhibitor that is a thymidine
analog approved by the FDA to treat acquired immune
deficiency syndrome (AIDS). The mechanism of action
includes phosphorylation of the drug in vivo to 3′-azido-3′deoxythymidine
triphosphate. This combines with human
immunodeficiency virus (HIV) reverse transcriptase, which
leads to cessation of DNA elongation.
zinc
An element of great significance to the immune system and
to other nonantigen-specific host defenses. The interleukins
of the immune system play a role in zinc distribution and
metabolism. As a constituent of the active sites in multiple
metalloenzymes, zinc is critical in chemical processes
within lymphocytes and leukocytes. Its role in the reproduction
of cells is critical for immunological reactions because
nucleic acid synthesis depends, in part, on zinc metalloenzymes.
Zinc facilitates cell membrane modification and
stabilization. Zinc deficiency is associated with reversible
dysfunction of T lymphocytes in humans. Thymic hormonal
function requires zinc; a deficiency causes atrophy
of the thymus and other lymphoid organs and is associated
with decreased lymphocytes in the T cell areas of
lymphoid tissues. Lymphopenia is also present. Anergy
develops in zinc-deficient patients and signifies disordered
cell-mediated immunity as a consequence of the deficiency.
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Z