Anthrax toxin effects on B lymphocyte function
dc.contributor.advisor | Johnny Peterson | en_US |
dc.contributor.committeeMember | Rolf Konig | en_US |
dc.contributor.committeeMember | Gustavo Valbuena | en_US |
dc.contributor.committeeMember | David Craft | en_US |
dc.creator | Bryan Thomas Gnade | en_US |
dc.date.accessioned | 2011-12-20T16:04:17Z | |
dc.date.available | 2010-09-28 | en_US |
dc.date.available | 2011-12-20T16:04:17Z | |
dc.date.created | 2010-03-11 | en_US |
dc.date.issued | 2010-01-11 | en_US |
dc.description.abstract | Bacillus anthracis is a gram-positive spore-forming rod capable of causing cutaneous, gastrointestinal and inhalational anthrax. It has a number of virulence factors of which, the two toxins are of great importance. Lethal toxin is a zinc metaloprotease that cleaves the N terminus of the mitogen-activated protein kinase (MAPK) kinase family 1-7, with the exception of MEK5. This kinase family is responsible for activating the mitogen-activated protein kinase (MAPK) cascade. This cascade includes extracellular signal-regulated protein kinases (ERK), c-Jun NH2-terminal kinases (JNK) and p38 kinases. The disruption of these signaling pathways has a number of deleterious downstream effects that vary by cell type. Edema factor is a powerful calmodulin-dependent adenylyl cyclase that forms 3’,5’-adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). This enzymatic reaction causes an increase in intracellular cyclic AMP (cAMP) in host cells. As cAMP is a prominent second messenger in cellular signaling, edema toxin has a wide array of effects on numerous cell types and functions. \r\nTo determine the effects of the anthrax toxins on the adaptive immune response, B lymphocytes were exposed to LeTx or EdTx in vitro. LeTx and EdTx both inhibit B cell activation in different manners. LeTx inhibited B cell proliferation but not migration, while EdTx inhibited B cell migration but not proliferation. LeTx and EdTx altered expression patterns of B cell activation markers. EdTx inhibited MIP-1α and MIP-1β while enhancing IL-6 production. Previously unseen in any cell type EdTx was demonstrated to be cytotoxic to naïve B cells.\r\nThe research presented in this report illustrates the inhibitory effects of LeTx and EdTx on B lymphocytes, providing valuable insight into the immunoevasion tactics of B. anthracis.\r\n | en_US |
dc.format.medium | electronic | en_US |
dc.identifier.other | etd-03112010-180727 | en_US |
dc.identifier.uri | http://hdl.handle.net/2152.3/40 | |
dc.language.iso | eng | en_US |
dc.rights | Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. | en_US |
dc.subject | lethal toxin | en_US |
dc.subject | edema toxin | en_US |
dc.subject | bacillus anthracis | en_US |
dc.subject | B cell | en_US |
dc.subject | anthrax toxin | en_US |
dc.subject | anthrax | en_US |
dc.title | Anthrax toxin effects on B lymphocyte function | en_US |
dc.type.genre | dissertation | en_US |
dc.type.material | text | en_US |
thesis.degree.department | Microbiology and Immunology | en_US |
thesis.degree.grantor | The University of Texas Medical Branch | en_US |
thesis.degree.level | Doctoral | en_US |
thesis.degree.name | PhD | en_US |