Accession Number:

ADA458915

Title:

The Host Immune Response to Streptococcus pneumoniae: Bridging Innate and Adaptive Immunity

Descriptive Note:

Doctoral thesis

Corporate Author:

UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD F EDWARD HEBERT SCHOOL OF MEDICINE

Personal Author(s):

Report Date:

2006-07-06

Pagination or Media Count:

140.0

Abstract:

Streptococcus pneumoniae Pn remains the primary cause of community-acquired pneumonia throughout the world, leading to high morbidity and mortality rates in the young and elderly. A better understanding of the host response to the organism would aid in the development of more effective antibiotics and vaccines. Toll-like receptors TLRs play an important role in the initial recognition of pathogens by binding conserved moieties known as pathogen associated molecular patterns PAMPs. This interaction is translated through the induction of signaling cascades that ultimately results in the production of various chemical mediators necessary for the activation of the adaptive arm of the immune response. Presentation of processed antigen in the context of major histocompatibility complex MHC by antigen presenting cells occurs, leading to effective help by primed T cells Teff to naive B cells in a process known as linked recognition. The activation and proliferation of B cells into mature plasma cells results in the development of appropriate antibody responses that are critically important in the clearance of extracellular bacteria such as Pn. These responses, however, need to be modulated so that inappropriate immune activation does not lead to anergy or over-responsiveness. The naturally occurring thymic population of CD4CD25 regulatory T cells Tregs survey and monitor the actions of Teff to prevent such inappropriate responses. In the following dissertation, I have used a murine model to study the host response to Pn. Specifically, I have focused on previous findings in the lab that suggested a possible role for Tregs as well as TLRs in our model system. I found that Tregs do not appear to play a part in modulating acute humoral responses to a bacterial pathogen such as Pn.

Subject Categories:

  • Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE