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dc.contributor.advisorReynolds, Bruce-
dc.contributor.authorCaon, Adrian-
dc.description.abstractThis study concerns the Neisser-Wechsberg (NW) phenomenon - a prozone phenomenon that commonly occurs in the complement-mediated bactericidal reaction. It involves the deviation of complement activity at relatively high levels of associated antibody. Thus, target bacteria survive in the presence of relatively Low dilutions of a hyperimmune antiserum but can be killed in the presence of higher dilutions. This study, together with other studies, indicate that the NW phenomenon is an in vívo phenomenon, and not just an ín vitro artefact. The humoral arm of immune defense is significantly weakened in hyperimmunized animals and in humans with chronic infections involving Gram-negative bacteria. The phenomenon is probably not the cause of chronic infection but is an important consequence and may have a role in sustaining such an infection. The system studied here consists of the Salmonella typhímurium M206 strain of bacterium, rabbit antisera raised against this bacterium, and human or guinea pig serum as the complement source. Bacteria, sensitized with a prozoning dilution of antiserum, stilI displayed the prozone phenomenon when washed and incubated with a complement source. significant cornplement consumption was shown to occur in the prozone situation and the consumption was dependent on the presence of target bacteria.Thus, deviation of complement activity in the bactericidal reaction appears to be associated with phenomena occurring on the surface of the target bacteria, rather than with interactíons between antiserum and complement in the fluid-phase. Two rabbits were periodicalty vaccinated with heat kitled bacteria over eight weeks and, unlike the bactericidal activity (I week after initial vaccination), prozoning activity appeared Iater (after 2-3 weeks) in the rabbit sera and peaked after four weeks.Hyperimmune antisera were subjected to single step and stepwise affinity chromatography on protein A-Sepharose columns and the prozoning activity was found to reside exclusively with the lgG immunoglobulins.Fractions containing lgA and IgM immunoglobulins did not display prozoning activity. IgG fractions, having different reactivities for protein A, were isolated and all contained prozoning antibody and all were able to fix complement. It is concluded that complement-fixing (bactericidal) IgG antibody is the immunoglobulin species responsible for the NW phenomenon. Adsorption studies, utilizíng mutant strains of various Salmonella species,showed that the prozoning antibody is specific for antigenic determinants associated with the bacterial lipopolysaccharide (LPS) (o-somatic antigens, in this system), and no other outer membrane (oM) component, As the isolation of specific prozoning antibody by elution from whole M2O6 cells or insolubilized LPS proved extremely difficult, it is concluded that this antibody is very avid' A protein A binding assay, that measures cell-bound IgG, was used to establish that near antigen-saturating levels of specific IgG antibody are required to effect the prozone Phenomenon- Through the use of certain R reagents (c-I42, C-EDTA, C-EGTA) and the demonstration of immune adherence with prozoning mixtures, it was established that both compì-ement pathways are activated to at least the C3 component in the NW phenomenon. Through the use of other R reagents (RaC6-9, C6-def RaC) and an assay to detect deviated lysis, it became apparent that the membrane attack complex (MAC) of complement is not formed or, once formed, cannot bind to an OM site where it can effect a lesion. Further, the prozone phenomenon was demonstrated with sheep red blood cells and 5. minnesota R595 cells sensitized with the LPS of s. typhimuTium c5; this constituted evidence for the cooperation of LPs-antibody complexes in promoting the fixation of MAC to cells, that are subsequently killed and lysed by it. the data allows the following speculations to be made, regarding the NW phenomenon. Avid TgG antibody quickly and efficiently covers the LPS antigens of the target bacteria- This dense cover imparts a highly hydrophobic character to the surface of these cells. Either, the formation of the Iarge, amphiphilic MAC of complement is sterically and electrostatically hindered or, once formed, is prevented from interacting with the LPS-antibody complexes. Any MAC, formed in the fluid-phase is quickly inactivated by the inhibitor, S-Proteinen
dc.titleThe Neisser-Wechsberg phenomenonen
dc.contributor.schoolDepartment of Microbiology and Immunologyen
dc.provenanceThis electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
dc.description.dissertationThesis (M.Sc.) -- University of Adelaide, Dept. of Microbiology and Immunology, 1983en
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