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Immunosenescence is characterized by a decreased ability of the immune system to respond to foreign antigens, as well as a
decreased ability to maintain tolerance to self-antigens. This results in an increase susceptibility to infection and cancer, and
reduced responses to vaccination. During senescence an imbalance between production and clearance of reactive oxygen species
and increased levels of oxidatively damaged biomolecules is also observed.
We present evidence that splenic and lymph nodal antigen presenting cells purified from old mice present an oxidatively
damaged proteome modified by carbonylation, advance glycation end products and lipid peroxidation. Using qualitative and
quantitative mass spectrometry we demonstrate that oxidative stress and endosomal accumulation of oxidatively modified
proteins interferes with the efficient processing of exogenous antigens. In support of a causative role for oxidized products in
the inefficient immune response, a decrease in oxidative stress improved the adaptive immune response to immunizing antigens.
These findings underscore a previously unrecognized effect of the age-dependent oxidatively damaged proteome on the induction
and regulation of the immune response.
Laura Santambrogio has completed his Ph.D from Padua University in Italy and postdoctoral studies from NYU and Harvard University. She is an
Associate Professor of Pathology, Immunology & Microbiology at Albert Einstein College of Medicine. She has published more than 80 papers in
reputed journals, serves as reviewer on several internationally recognized journals as well as on different NIH study sections.
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