Books > Medicine > Clinical & internal medicine > Diseases & disorders > Immunology
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Molecular and Cellular Mechanisms of Antibody Activity (Hardcover, 2013 ed.)
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Molecular and Cellular Mechanisms of Antibody Activity (Hardcover, 2013 ed.)
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This book focuses on the function of antibodies in vivo. Recent
years have seen an exponential growth in knowledge about the
molecular and cellular mechanisms of antibody activity. These new
results dramatically changed our view of how antibodies function in
vivo. The importance of this class of molecules is demonstrated by
the heightened susceptibility to infections of humans and mice with
an altered capacity to generate pathogen specific antibody
responses. Thus, the majority of our currently available vaccines,
such as vaccines against influenza, measles and hepatitis focus on
the generation of long lasting antibody responses. Recent evidence
from a variety of in vivo model systems and from human patient
cohorts has highlighted the exclusive role of cellular Fc-receptors
for certain immunoglobulin isotypes and subclasses. With the recent
discovery of a human Fc-receptor for IgM all different human
immunoglobulin isotypes now have a cellular receptor, providing a
feedback mechanism and link between antibodies and the cellular
components of the immune system. Moreover it has become clear the
complement and Fc-receptor system are tightly connected and
regulate each other to ensure a well balanced immune response.
Among the immunoglobulin isotypes IgG plays a very important
protective role against microbial infections and also as a
therapeutic agent to kill tumor cells or autoantibody producing B
cells in autoimmune disease. Transfer of our knowledge about the
crucial function of Fc-receptors has led to the production of a
second generation of therapeutic antibodies with enhanced binding
to this class of receptors. Binding of antibodies to Fc-receptors
leads to the recruitment of the potent pro-inflammatory effector
functions of cells from the innate immune system. Hence,
Fc-receptors link the innate and adaptive immune system,
emphasizing the importance of both arms of the immune system and
their crosstalk during anti-microbial immune responses. Besides
this pro-inflammatory activity immunoglobulin G (IgG) molecules are
long known to also have an anti-inflammatory function. This is
demonstrated by the use of high dose intravenous immunoglobulins as
a therapeutic agent in many human autoimmune diseases. During the
past five years several new insights into the molecular and
cellular pathways of this anti-inflammatory activity were gained
radically changing our view of IgG function in vivo. Several lines
of evidence suggest that the sugar moiety attached to the IgG
molecule is responsible for these opposing activities and may be
seen as a molecular switch enabling the immune system to change IgG
function from a pro- to an anti-inflammatory activity. There is
convincing evidence in mice and humans that aberrant IgG
glycosylation could be an important new pathway for understanding
the impaired antibody activity during autoimmune disease. Besides
this tremendous increase in basic knowledge about factors
influencing immunoglobulin activity the book will also provide
insights into how these new insights might help to generate novel
therapeutic approaches to enhance IgG activity for tumor therapy on
the one hand, and how to block the self-destructive activity of IgG
autoantibodies during autoimmune disease on the other hand.
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