460
Autoantibodies and Autoimmunity
Immunogen
A substance that elicits an antibody response.
Indirect Immunofluorescence (IIF)
A technique whereby an antibody is overlaid onto an antigen containing cellular
substrate and the antigen–antibody formed complex is detected by a fluorescently
labeled anti-antibody.
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Autoimmunity is an immunological reaction against constituents of the organism
that are normally tolerated by the immune system of that organism. Autoimmune
reactions can be either cell- or antibody-mediated. Autoantibodies are therefore
antibodies that recognize normally tolerated cell and tissue constituents (or
autoantigens). The antigenic speciFcity of an autoantibody can be a useful aid
in clinical diagnosis. Autoantibodies are either cell (or tissue) speciFc, as found in
organ-speciFc autoimmune diseases such as autoimmune thyroiditis, or non–organ-
speciFc and reactive with ubiquitous intracellular antigens, as found in multisystem
autoimmune diseases such as the systemic rheumatic diseases. The latter group
includes autoantibodies that recognize components of macromolecular complexes
of nucleic acids and/or proteins such as small nuclear ribonucleoprotein (snRNP)
particles, nucleosomal and subnucleosomal structures, and tRNA synthetases, which
are intrinsic components of all cell types present in an organism. Autoantibodies also
recognize components of subcellular structures, including mitochondria, ribosomes,
Golgi apparatus, nuclear membrane, and substructures within the nucleus and
nucleolus. The ability of autoantibodies to recognize components of the cellular
machinery of replication, transcription, RNA processing, RNA translation, and
protein processing has made them important reagents for isolating cDNA clones that
code for proteins involved in these cellular processes and for probing the relationship
between molecular and cellular structure and function. The evolutionarily conserved
nature of many autoantigens allows the use of autoantibodies to identify their target
antigens in diverse species, ranging in some cases from humans to lower eukaryotes
such as yeast. Autoantibodies have been used to inhibit the biological function of
autoantigens and/or to recognize autoantigens in a deFned functional state.
1
Autoantibodies and Autoimmunity
An autoimmune response is an attack by
the immune system on the host itself. In
healthy individuals, the immune system is
‘‘tolerant’’ of its host (‘‘self’’) but attacks
foreign (‘‘nonself’’) constituents such as
bacteria and viruses. The ability to distin-
guish self from nonself is considered to
be the determining factor in whether the
immune system responds to a suspected
challenge. Although it may appear obvious,
there is actually considerable debate over
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