| Immunology as a section of
the diagnostic clinical laboratory has increased in scope
tremendously. New knowledge about cellular immunity, including
lymphocyte subsets, and advances in protein chemistry, bacteriology
and cell biology have increased our understanding of human
immunopathology, and at the same time has made available clinically
useful antigens and antibodies with great specificity and sensitivity.
The developing technologies of monoclonal antibody production and
genetic engineering will have a tremendous impact on the quality of
reagents available to research and clinical laboratories.
Another great improvement has been the
development of tests specifically for IgM antibodies. These are the
first antibodies produced in an organism's first encounter with an
antigen, and thus their presence is strong evidence of acute exposure.
Therefore, while in the serologic diagnosis of infectious disease it
is still true as a rule of thumb that the fourfold increase in
antibody titer is the most convincing evidence of infection, the
demonstration of specific IgM antibody is achieving equal status as a
diagnostic tool.
Not only have classical serologic tests
for infectious or inflammatory processes benefited from new conceptual
and technological advances, "reagent immunology" now has a
foot in the door of every laboratory section. The industry's ability
to create antibodies to drugs, proteins, polypeptides, and large
molecules, and then to link those antibodies to enzymes, radioactive
tracers, solid supports or fluorescent tags has led to the development
of a wonderful variety of sensitive, specific assays with great
accuracy and precision. With monoclonal antibodies available we can
expect even more and better tests.
The Power of the Immune System for Diagnosis and Treatment of Diseases
In the 1995 presidential address of the
American Association of Immunologists, Dr. Irving L. Weissman
summarized the power of using the immune system for the diagnosis and
treatment of diseases. He also listed some of the current realities of
immunological achievements that have advanced biomedical science.
First, we now know that autoimmunity is
real, and is often T-cell and sometimes B-cell based. We can even
identify certain genetic predictors, such as disease associated MHC
alleles, involved T-cell receptors, and types of antibody sequences in
autoimmune states as diverse as Type I diabetes, multiple sclerosis,
and rheumatoid arthritis. We also now know that for many cancers
-melanoma and breast cancer are examples- there are defined peptides
from the tumors that can and do excite particular MHC Class I
restricted cytolytic T-cell responses. Humanized monoclonal antibodies
to a number of clinical targets are making their way into the field
after the first round of mouse monoclonal antibodies proved
immunogenic, or directed against the wrong targets.
The role of antigen-presenting cells,
and how they are differentiated and charged with antigen, is now be
coming important in the area of vaccine development. Purified
hematopoietic stem cells and other hematopoietic progenitors are
making their way through clinical trials. These stem cells are already
being engineered to yield progeny resistant to agents such as HIV and
chemotherapeutic drugs, or to express transgenes that enhance immune
resistance to tumors and infections.
The inflammatory components of major
diseases, whether autoimmune or post-vascular injury, are now being
understood on the basis of homing receptor/adhesion molecules
expressed on circulating blood elements, and complementary ligands
that are expressed on normal, inflamed, and injured endothelia.
Humanized antibodies, synthetic and natural carbohydrates, and other
small molecules that block these inflammatory adhesion molecules are
making their way to the clinic at this time.
Finally, but not last on this
incomplete list of possible topics, the understanding of T-cell
development and function and an understanding of how HIV interferes
with this, is leading to new paradigms to try to counter the AIDS
epidemic.
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