Browsing by Subject "Immune response."
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Item A possible mechanistic role for microorganisms in the genesis of colorectal cancer.(2013-09-24) Butcher, Lindsay D.; Boland, C. Richard, 1947-; Biomedical Studies.; Eureka Genomics.; Baylor University. Institute of Biomedical Studies.Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. An estimated over 140,000 people will be diagnosed with CRC and over 50,000 people will die in 2013. CRC tumors develop from a polyp but the initial cause of the chromosomal instability and mutations is unknown. Microorganisms are shown to be involved in other cancers so it is possible one may be involved with CRC. Identification of the organism may help prevention, diagnosis and treatment. Previous work in our lab identified the presence of JC virus (JCV) and increased expression of a protein in colorectal neoplasms compared to normal colon tissue. JCV is a polyomavirus that infects approximately 75% of the population. Polyomaviruses are DNA viruses and one of the proteins encoded in the genome is the T Antigen. The T Antigen protein is oncogenic and is capable of inactivating p53 and the pRb/p107/p130 protein families. While JCV remains in a latent state for the majority of those infected, we hypothesized that a disturbance to the immunological control allows for JCV to be active again and that the T Antigen may be involved in the development of colorectal neoplasms. Knowing the section T antigen protein that is most immunogenic and the ensuing immune response in patients with and without colon neoplasia will create a foundation to better understand the viral mechanism of action in the colon. Next generation sequencing allows for better identification of the colon microbiome. Using DNA from surgically removed colon tissues, we determined the presence of microorganisms in the colonic epithelium using next generation sequencing. One microorganism isolated was predominately in colon tumors and the adjacent normal tissue but was seen at much lower levels in adenomatous polyps or normal tissue without a tumor present. This microorganism may contribute to or be an indicator of CRC. Which microorganisms are present and the immune response to them will help identify their role in the development of CRC. Our studies evaluated the immune response to one virus and identified another possible microorganism that may be associated with colorectal carcinogenesis.Item Respiratory syncytial virus subverts the immune response by inhibiting myeloid dendritic cell function.(2009-07-01T17:02:09Z) Xu, Chuang.; Connolly, John Edward.; Biomedical Studies.; Baylor University. Institute of Biomedical Studies.Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and young children. Antigen presentation by dendritic cells (DCs) is critical for the establishment of antiviral immunity and DCs are frequent targets of viral immune evasion. Upon activation, DCs undergo maturation during which they highly upregulate the surface expression of MHC class II, a molecule critical for the presentation of exogenous antigen to CD4+ T cells. MHC class II biosynthesis and surface expression is a multi-stage process which is controlled by a variety of positive and negative regulatory molecules. Here we show that DC exposed to RSV both in vivo and in vitro failed to elicit a mixed leukocyte reaction (MLR). Furthermore, RSV exposed DCs inhibited allogeneic proliferation from unexposed DCs in trans, in a cell contact dependent mechanism. Consistent with their impaired antigen presenting ability, both primary blood mDCs exposed in vitro to RSV and nasal mucosa mDC from RSV patients failed to upregulate MHC class II. MHC class II levels remained low despite the apparent upregulation of other markers of DC maturation such as MHC class I, CD83, CD86 and CD40. This inhibition could not be explained by the reduced bio-synthesis of MHC class II as class II transactivator (CIITA) level remained unchanged and the total cellular HLA-DR was comparable to mDCs exposed to influenza virus (FLU). Furthermore, SDS stability assay showed similar level of MHC class II peptide complex between the two viral treatments, indicating RSV exposure did not block class II loading. Consistent with the reduced surface expression, confocal microscopy demonstrated a selective blockade of MHC class II surface translocation by RSV. Blockade of class II surface translocation was dependent on viral fusion (F) protein expression. In addition, RSV induced the expression of a novel splice variant of HLA-DO, a negative regulatory molecule in the MHC class II presentation pathway. Taken together, these results demonstrate that RSV blocks DC antigen presentation by inhibiting surface class II peptide complex formation at multiple stages and suggest a novel mechanism of viral immune evasion.