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side effect 653 autoantibodies (SRP autoantibodies)
Side-Chain Theory, continued.
substances to the cell prior to internalization. These side chains
or receptors were considered to permit cellular interaction with
substances in the extracellular environment. Antigens were
postulated to stimulate cells by attachment to the receptors.
Because antigens played no part in the normal cell economy,
the receptors were diverted from their normal function.
Stimulated by this derangement of their normal mechanism,
cells produced excessive new receptors of the same type as
those thrown out of action. The superfluous receptors were shed
into the extracellular fluids and constituted specific antibodies
with the capacity to bind homologous antigens. Ehrlich
proposed a haptophore group that reacted with a corresponding
group of an antigen, as in neutralization of toxin by antitoxin.
For reactions such as agglutination or precipitation, he postulated
that another (ergophobe) group determined the change
in antigen after the antibody was anchored by its haptophore
group. Ehrlich proposed receptors with two haptophore groups:
one that attached to antigen and the other to complement.
The group that combined with the cell or other antigen was
called the cytophilic group, and the group that combined with
complement was the complementophilic group. Ehrlich called
these types of receptors amboceptors because both groups were
supposed to be of the haptophore type. He considered a toxin to
have a haptophore group and a toxophore group. Detoxification
without loss of antitoxin-binding capacity led Ehrlich to believe
that a toxophore group was altered while the haptophore group
remained intact. His theory assumed that each antibody-forming
cell had the ability to react to every antigen in nature. The
demonstration by Landsteiner that antibodies could be formed
against substances manufactured in a laboratory and never
present in nature led to abandonment of the side chain theory
although its basic premise as a selective hypothesis rather than
an instructive theory was ultimately proven correct.
side effect
An unwanted reaction to a drug administered to achieve a
desirable curative or other effect.
signal hypothesis
A proposed mechanism for selection of secretory proteins by
and for transport through the rough endoplasmic reticulum.
The free heavy and light chain leader peptide is postulated to
facilitate the joining of polyribosomes forming these molecules
to the endoplasmic reticulum. The hypothesis also cites
the release of heavy and light polypeptide chains through the
endoplasmic reticulum membrane into the cisternal space
followed by immunoglobulin secretion after the immunoglobulin
molecule has been assembled and to the pathways
whereby proteins reach their proper cellular destinations.
Important to protein targeting is the signal sequence—a short
amino acid sequence at the amino terminus of a polypeptide
chain. This signal sequence directs the protein to the proper
destination in a cell and is removed during passage or when
the protein arrives at its final location.
signal joint
A structure produced by the precise joining of recognition
signal sequences during somatic recombination that
produces T cell receptor (TCR) and immunoglobulin (Ig)
genes. The DNA sequence produced by uniting of blunt
RSS ends after V(D)J recombination of gene segments.
signal pathway DNA-binding proteins
Because DNA-binding proteins are made in genes distant
to their sites of activity, they are designated trans-acting.
These proteins are transcription factors that interact with
enhancers and promoters by binding to unique nucleotide
sequences. Due to these interactions, DNA-binding proteins
regulate the transcription of the genes under the influence
of each promoter or enhancer. They are important means of
signal transduction through which external stimuli induce
responses at the nuclear level.
signal peptide
The small leader sequence of amino acids that shepherds
the heavy or light chain through the endoplasmic reticulum
and is cleaved from the nascent chains prior to assembly of
a completed immunoglobulin molecule.
signal recognition particle
autoantibodies (SRP autoantibodies)
Autoantibodies against SRP such as mitochondrial, ribosomal,
and certain cytoplasmic autoantibodies that stain
Hep-2 cell cytoplasm and can be assayed by radioimmunoprecipitation
assay (RIPA), enzyme immunoassay (EIA), and
cytoplasmic (non-Jo-1) fluorescence in approximately 4% of
polymyositis/dermatomyositis (PM/DM) patient sera. SRP
autoantibodies characterize a homogeneous group of patients
with similar clinical features (typically black females with
acute onsets of severe polymyositis together with cardiac
involvement and resistance to therapy, including corticosteroids);
mortality is 75% at 5 years. SRP autoantibodies are
not usually detected in patients with arthritis, dermatomyositis,
pulmonary fibrosis, or Raynaud’s phenomenon.
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