This study was designed to examine the immunological privilege of the hamster cheek pouch. A comparison of the cheek pouch with the non-immunologically privileged flank was carried out by investigating responses to Glaxo BCG at the tissue, cellular and humoral levels using Histological methods, Mantoux Tests, Lymphocyte Transformation Tests, Passive Haemagglutination Tests and Immunoelectrophoresis Tests. These studies showed no differences in the responses to BCG in the cheek pouch or flank but do not preclude the possibility that the responses elicited in the cheek pouch differed qualitatively or quantitatively from those in the flank. In response to a single injection of BCG into the cheek pouch or flank compact and non-caseating epithelioid cell granulomas developed locally, with no evidence of the infection extending into the surrounding tissue or progressing to peripheral sites in the body. These findings could be related to the low virulence of Glaxo BCG for the hamster. Animals that had received a single injection of BCG or a rechallenge injection of BCG in Incomplete Freund's Adjuvant (IFA), were Mantoux negative and may also be related to the low virulence of Glaxo BCG for the hamster. The levels of specific and non-specific lymphopro-liferation to BCG and PHA, respectively were biologically insignificant in animals that had received a single injection of BCG and in those that had received a rechallenge injection of BCG in IFA. These findings can probably be attributed to the conditions of culture in the Lymphocyte Transformation Test. No specific agglutinating antibody was detected in the sera of animals that had received a single injection of BCG or a rechallenge injection of BCG in IFA. These findings could be related to the unreliability or lack of sensitivity of the Passive Haemagglutination Test.

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Ferredoxin (Fd), a fifty-five amino acid electron transport protein of the anaerobe Clostridium pasteurianum, has been chosen as the ideal probe for immunoregulation studies. Its critical feature is that it contains two antigenic determinants satisfying the hypothetical minimum requirement for immunogenicity. It was found that both the antibody (as measured by ELISA) and the lympho-proliferative responses to Fd are linked exclusively to the MHC of mice, mapping to K/I-A. Analysis of the response was undertaken at the determinant level with selective enzyme cleavage products of trypsin and carboxypeptidase A which yield respectively a 52 residue C-determinant peptide (devoid of a functional N-determinant), "C", and a 53 residue N-determinant peptide (devoid of a functional C-determinant peptide), "N",. Through the use of these two molecules ("N" and "C") and a doubly digested molecule, "M", the immune response to Fd was dissected. At first, anti-Fd antibody from high responder, H-2[sup=k], mice was shown to be 10-20% "N" specific with the balance of the response "C" directed, while intermediate responder haplotypes, H-2[sup=b] and H-2[sup=s]. demonstrate equal specificity for the two determinants. H-2 mice were uniformly non-responsive. Fd immune T-cells demonstrated lymphoproliferative capacity mirroring the antibody response of B10.BR (H-2[sup=k]) mice: "C" induced proliferation comparable to that with the native molecule, "N" inducing a much lower response, one matched by the "M" peptide. Next, the "N", "C" and "M" molecules were assessed for their immunogenicity in B10.BR, C57BL/10 (H-2[sup=b])and B10.D2 (H-2[sup=d]) mice. "N" was found to induce limited, if any, antibody production whereas it primes for a very good proliferative response (B10.BR only). "M" induced no antibody response in any strain, and minimal proliferation in B10.BR. "C" induced at least two-fold higher antibody in B10.BR and C57BL/10 as compared to native Fd, and converted the B10.D2 non-responders into responders. "C" induced a weak proliferative response in B10.BR. The data suggest that two determinants exist at the B-cell level, while three determinants account for the T-cell response. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

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MSc (Med), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Background: RTS,S candidate malaria vaccine has been shown to be highly immunogenic in children and infants, but the protective immune mechanisms still remain to be clearly elucidated. It is believed that RTS,S elicits a strong neutralizing humoral immune response directed against surface-exposed sporozoite proteins and cell mediated immune (CMI) responses characterized by predominantly CD4+ Th1 cells. The objective of this study was to investigate humoral and cell-mediated immune responses to the RTS,S/AS02D malaria vaccine and its association with protection against infection and disease by P. falciparum. Methodology and Principal Findings: This secondary data analysis from data of a phase I/IIb randomized, double-blind, controlled trial, included 154 healthy infants living in rural Mozambique, previously immunized with RTS,S/AS02D candidate malaria vaccine or the control Engerix-B™ vaccine. Antibodies against circumsporozoite protein (CSP) and hepatitis-B surface antigen (HBsAg) were measured with a standard ELISA. Fresh blood intracellular staining assay was performed to evaluate the expression of IL-2 and IFN-γ by CD4+ and CD8+ cells in response to in vitro stimulation of specific peptides. Data was evaluated for association with the risk of malaria detected by both active and passive case detection of infection over a period of 6 months post dose 3. Anti-HBs antibody geometric mean titers declined from 10,082 mIU/mL one month post Dose 3 to 2,751 mIU/mL at 12 months post Dose 3 in the RTS,S/AS02D group; anti-HBs v geometric mean titers were 392.4 mIU/mL and 263.9 mIU/mL, respectively in the Engerix- BTM group. Anti-CSP antibody geometric mean titers declined from 199.9 EU/mL one month post Dose 3 to 7.3 EU/mL at 12 months post Dose 3 in the RTS,S/AS02D group. Median stimulation indices of HBs-specific IL-2 and IFN-γ producing CD8+ T cells was higher in the RTS,S/AS02D group than in control group (Wilcoxon rank sum p-values for IFN-γ = 0.015, for IL-2 = 0.030) at 10.5 weeks post immunization. Median stimulation indices of anti-CSP specific IFN-γ producing CD8+ T cells at the same time point was 1.13 (IQR: 0.79 - 1.67; p=0.029). For specific IL-2-producing CD4+ T cells, the median SI was 1.14 (IQR: 0.74 – 1.60, p=0.043) at 10.5 weeks post dose three. The reduction in hazards of malaria infection were 18.3 % (95% CI: -267.9 – 81.8, p=0.793) and -12.0 % (95% CI: -295 – 68.2, p=0.86) for specific IL-2 CD4+ stimulation indices; For specific CD8+ IFN-γ stimulation indices the hazards were -103.6% (95% CI: -690.9 – 47.6; p=0.305) and 48.8% (95% CI: -97.0 – 86.7; p=0.33) at four and 10.5 weeks post immunization respectively. Conclusion: The RTS,S/AS02D vaccine was immunogenic and has elicited detectable levels of CSP specific cell mediated responses. No evidence of association was found between the antibodies anti-CSP and specific cell mediated responses and the risk of malaria.

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Sleep loss is known to trigger an inflammatory response and increase serum corticosterone in both human and murine models. However, very little evidence is available on the potential effects of sleep loss in avian models. This study aims to construct a profile using cytokine gene expression data to determine how birds respond to sleep loss in a controlled environment. I investigated changes in pro-inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine gene expression in the periphery (fat, liver, spleen, and heart) and brain (hypothalamus, hippocampus, and apical hyperpallium) in zebra finches exposed to a novel sleep fragmentation method. Serum corticosterone, body mass, and behavioral profiles also were assessed. Sleep was interrupted periodically for over 12 hours using a sleep fragmentation chamber, which was modified from those typically used in murine studies. This chamber contained a sweeping wire bar that moved the distance of the cage at 2-minute intervals. I predicted that sleep fragmented birds would exhibit elevated pro-inflammatory and reduced anti-inflammatory gene expression relative to those birds that were not sleep fragmented. In addition, I predicted a decrease in body mass and an increase in serum corticosterone levels because of sleep fragmentation. Contrary to my predictions, sleep fragmentation resulted in lower levels of IL-1β in the apical hyperpallium, but lower levels of IL- 10 in the hippocampus. No differences were detected in the adipose tissue of individuals exposed to sleep loss. Sleep fragmentation resulted in an increase in percent body mass lost. Serum corticosterone levels did not differ across groups. These data provide preliminary insight into the inflammatory response that is seen as a result of sleep loss in an avian model. Overall, it appears that as compared to some mammals such as murine rodents, birds are not as susceptible to sleep loss.

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No description available.