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cytotoxicity tests 213 cytotropic anaphylaxis
INFγ
INFα/β
Tc cell or
CTL precursor
Tumor cell
INF γ
CTL
differentiation
Cytotoxic
T Lymphocyte
(CTL)
induced can be programmed cell death (apoptosis), in which
the nuclear DNA of the dying cell disintegrates and the
cell membrane increases in permeability, or the cell death
may be the result of necrosis that does not involve active
metabolic processes and leads to increased membrane
permeability without immediate nuclear disintegration.
Cell-mediated cell lysis usually induces apoptosis, whereas
antibody and complement usually induce necrosis. Cell
death is determined by measurement of increased membrane
permeability and by detecting DNA disintegration.
The two methods used to determine membrane permeability
of cells are dye exclusion, in which Trypan blue is used
to stain dead cells but not viable ones, and the chromium
release assay, in which target cells are labeled with radioactive
51 Cr, which is released from cells that develop increased
membrane permeability as a consequence of immune
attack. To quantitatively measure either DNA disintegration,
125 IUdR or 3 H-thymidine can be used to label nuclear
DNA.
cytotoxicity tests
(1) Assays for the ability of specific antibody and complement
to interrupt the integrity of a cell membrane, which
permits a dye to enter and stain the cell. The relative proportion
of cells stained, representing dead cells, is the basis
for dye exclusion tests. Refer to microlymphocytotoxicity.
(2) The ability of specifically sensitized T lymphocytes to
kill target cells, the surface epitopes of which are the targets
of their receptors. Loss of the structural integrity of the
cell membrane is signified by the release of a radioisotope
TCR
Epitope
MHC class I
receptor
CD8+
Perforin and
granzymes
Tumor cell
Cytotoxic T lymphocytc (CTL)-mediated tumor lysis.
MHC class I
receptor
Increase in
MHC class I
expression
CD8 + T cell
Epitope
TCR CD8 +
Cytotoxic
T Lymphocyte
(CTL)
TCR
CD8 +
MHC class I
receptor
Perforin
and
granzymes
Cytotoxic T lymphocytc (CTL)-mediated killing of tumor cells.
Tumor cell
Tumor cell
lysis
Tumor cell
lysis
such as 51 Cr, which has been taken up by the target cells
prior to the test. The amount of isotope released into the
supernatant reflects the extent of cellular injury mediated by
the effector T lymphocytes.
cytotoxins
Proteins synthesized by cytotoxic T lymphocytes that facilitate
target cell destruction. Cytotoxins include perforins and
granzymes or fragmentins, and granulysin.
cytotrophic antibodies
Immunoglobulin E (IgE) and IgG antibodies that sensitize
cells by binding to Fc receptors on their surface, thereby
sensitizing them for anaphylaxis. When the appropriate
allergen crosslinks the Fab regions of the molecules, it leads
to the degranulation of mast cells and basophils bearing IgE
on their surface.
cytotropic anaphylaxis
Form of anaphylaxis caused by antigen binding to reaginic
IgE antibodies. The latter are cytotropic; that is, they
bind to cells. Cytotropic antibodies (immunoglobulin E
[IgE]) bind to specific receptors on the mast cell surface.
The receptors are in close proximity to a serine esterase
enzyme, causing the release of mast cell granules, and to a
natural inhibitor of this enzyme. As long as the surface IgE
has not bound antigen, the status quo of the cell is maintained.
It is believed that binding of the antigen induces a
conformational alteration in the IgE, with displacement of
the inhibitor from its steric relationship to the enzyme. The
inhibition-free enzyme mediates the release. The process
requires energy and is Ca 2+ dependent.
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