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Host/pathogen interactions: A study of Yersinia pseudotuberculosis pathogenesis and host immune response

Posted on:2003-06-04Degree:Ph.DType:Thesis
University:Stanford UniversityCandidate:Yao, Tony Dung-LingFull Text:PDF
GTID:2464390011982643Subject:Health Sciences
Abstract/Summary:
Death and morbidity from infectious organisms have long been a problem for the human race, and since ancient times, scientists have studied both the mechanisms that the body uses to prevent or combat infection as well as the strategies that pathogens use to cause infection. As great strides have been made, it has been recognized that both pathogen virulence and host immune response are incredibly complex processes. On one side, the pathogen must have mechanisms to invade the host, extract nutrients, and avoid immunological clearance. The host's immune system, on the other hand, must have the means to resist the pathogen and ultimately generate a sterilizing response. While there are many approaches to study infection, this thesis focuses on the direct interactions of pathogen with the host immune system using a murine Y. pseudotuberculosis infection model. Yersinia is shown to have the ability to directly interfere with the function of both T and B cells through the use of two of its virulence factors, YopH and YopJ. YopH, a tyrosine phosphatase, can rapidly inhibit the tyrosine phosphorylation dependent antigen receptor signaling pathway in lymphocytes. YopJ and YopH, through unknown mechanisms, are able to inhibit B cell activation in response to the presence of gram negative bacteria, as measured by cytokine production and upregulation of immunocostimulatory molecules. These novel virulence strategies may play an important role in Yersinia infection. In vivo investigations on the role of B cells during infection reveal the surprising finding that mice, in the absence of B cells, are actually more resistant to Y. pseudotuberculosis infection compared to wild type mice. New Yersinia virulence strategies as well as a novel role for B cells during early infection is discussed.
Keywords/Search Tags:Yersinia, Hostimmune, Infection, Pathogen, Pseudotuberculosis, Response, Virulence
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