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Antigen acquisition by dendritic cells: A focus on transfer between live cells

Posted on:2003-11-27Degree:Ph.DType:Dissertation
University:University of PittsburghCandidate:Harshyne, Larry Alan, JrFull Text:PDF
GTID:1464390011986223Subject:Health Sciences
Abstract/Summary:
Dendritic cells (DC) exist throughout the periphery. In the skin and mucosa, they are immature in nature and act as sentinels for the immune system. These immature cells are proficient phagocytic cells that continually peruse the local environment for antigen. Upon acquiring antigen, DC enter lymphatics and migrate to draining lymph nodes. During this period they undergo a change in their maturational program and down-regulate the ability to acquire antigen and up-regulate molecules that facilitate interaction with and activation of naive T cells. In the lymph node, DC home to the paracortex where they encounter large numbers of naive T cells. Once a T cell forms an antigen-specific interaction, the T cell becomes activated and begins to proliferate. Here, the DC life cycle finishes, but their legacy lives on as masses of antigen-specific T cells migrate to the site of infection and destroy the invading pathogen.;Infectious diseases are a major global health problem. Human immunodeficiency virus (HIV), tuberculosis (TB), and malaria are the biggest killers worldwide claiming 3 million, 2 million, and 1 million plus lives each year, respectively. While the infectious organism in each case may be different, as HIV is a virus, TB is caused by a bacterium, and malaria is caused by a parasite, the survivors, are so, because their DC have successfully stimulated an immune response. The mission in all three instances remains the same, to develop (better) vaccines to combat these infectious diseases, which in some form or another will undoubtedly involve DC.;These studies identified a novel form of antigen uptake utilized by DC, the receptor mediating this process, and a detailed characterization of the mechanism underlying live-cell antigen capture by DC, thereby expanding our knowledge of antigen presentation and basic DC biology. These findings can be integrated into DC vaccine or therapy protocols by targeting antigen directly to DC via SR-A, in hopes of improving prevention/treatment of not only infectious diseases, but also tumors and autoimmune disease.
Keywords/Search Tags:Cells, Antigen, Infectious diseases
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