Anthrax toxin effects on B lymphocyte function

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Anthrax toxin effects on B lymphocyte function

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dc.contributor.advisor Johnny Peterson 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.identifier.other etd-03112010-180727 en_US
dc.identifier.uri http://hdl.handle.net/2152.3/40
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.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.material text en_US
dc.type.genre dissertation en_US
thesis.degree.name PhD en_US
thesis.degree.level Doctoral en_US
thesis.degree.grantor The University of Texas Medical Branch en_US
thesis.degree.department Microbiology and Immunology en_US
dc.contributor.committeeMember Rolf Konig en_US
dc.contributor.committeeMember Gustavo Valbuena en_US
dc.contributor.committeeMember David Craft en_US

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