Thesis (Ph. D.)--University of Missouri--Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves : [128]-155). Also available on the Internet.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [105]-120).

Thesis (M.Sc.)--Memorial University of Newfoundland, 2002. / Restricted until June 2003. Bibliography: leaves 189-214.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 71-80).

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Experimental Medicine, Department of Medicine. Title from pdf file main screen (viewed on April 24 2010). Includes bibliographical references.

Thesis (Ph. D.)--Oregon State University, 2011. / Printout. Includes bibliographical references (leaves 92-102). Also available on the World Wide Web.

To detect viral infections and tumors, CD8 T lymphocytes monitor cells for the presence of antigenic peptides bound to MHC class I molecules. The majority of MHC class I-presented peptides are generated from the cleavage of cellular and viral proteins by the ubiquitin-proteasome pathway. Many of the oligopeptides produced by this process are too long to stably bind to MHC class I molecules and require further trimming for presentation. Cytosolic aminopeptidases such as leucine aminopeptidase (LAP), which is IFN-inducible, Bleomycin Hydrolase (BH), and puromycin-sensitive aminopeptidase (PSA) can trim precursor peptides to mature epitopes and have been thought to play an important role in antigen presentation. To examine the role of these aminopeptidases in generating MHC class I peptides in vivo, we generated mice deficient in LAP or PSA, as well as cell lines deficient in LAP, PSA, or BH. LAP mutant mice and cells are viable and grow normally, whereas PSA mutant mice are smaller than their wild-type and heterozygote littermates, are subfertile as adults, and are subviable as embryos. The trimming of peptides in LAP-deficient cells is not reduced under basal conditions or after stimulation with IFN. Similarly, there is no reduction in presentation of peptides from precursor or full length antigen constructs or in the overall supply of peptides from cellular proteins to MHC class I molecules, even after stimulation with IFN. After viral infection, LAP-deficient mice generate normal CTL responses to seven epitopes from three different viruses. Similarly, PSA deficient mice and BH deficient mice generate normal CTL responses to viral epitopes. These data demonstrate that LAP, BH, and PSA are not essential enzymes for generating most MHC class I-presented peptides and reveal redundancy in the function of cellular aminopeptidases in most cell types.

An optimal antibody response to a thymus-dependent antigen requires cooperation between the B cell and an antigen-specific helper T cell. Major histocompatibility complex restriction of this interaction implies that the helper T cell recognizes antigen on the B cell surface in the context of MHC molecules, and that the antigen-specific B cell gets help by acting as an antigen presenting cell for the helper T cell. However, a number of studies have shown that normal resting B cells are ineffective as antigen presenting cells, implying that the B cell must leave the resting state before it can interact specifically with a helper T cell. On the contrary, other studies, including those using rabbit Ig as antigen, and rabbit globulin-specific mouse T cell lines and hybridomas, show that certain T cell lines can be efficiently stimulated by normal resting B cells. One possibility I considered was that small B cells are unable to process antigens, and that the rabbit Ig-specific T cell lines used above recognize native antigen on the B cell surface. In the majority of cases, experiments with B cell lines and macrophages have shown that antigen presentation requires antigen processing, a sequence of events which includes: internalization of antigen into an acid compartment, denaturation or digestion of antigen into fragments, and the return of processed antigen to the cell surface where it can then be recognized by the T cell in the context of class II molecules of the MHC. The experiments reported here show that the rabbit Ig-specific T cell lines do require an antigen processing step, and that small resting B cells, like other antigen presenting cells, process antigen before presenting it to T cells. Specifically, I show that an incubation of 2-8 hours is required after the antigen pulse before antigen presentation becomes resistant to fixation or irradiation. Shortly after the pulse, the antigen enters a pronase resistant compartment. Chloroquine, which raises the pH of endocytic vesicles, inhibits presentation. In addition, a large excess of antibody to native antigen fails to block presentation of antigen after a 2-8 hour incubation. Also, although membrane Ig, the antigen receptor on the B cell, is required for efficient presentation of antigen at low concentrations, antigen is no longer associated with the B cell receptor at the time of presentation to the T cell. Modulation of membrane Ig by anti-Ig blocks presentation before but not after the antigen pulse.

Enxerto ósseo homólogo é utilizado independentemente da compatibilidade HLA entre doador e receptor ou uso de drogas imunossupressoras. Considerando o volume de transplantes ósseos realizados no Brasil e o possível efeito deletério da sensibilização HLA para o transplante de órgãos sólidos, este estudo tem como objetivo avaliar a alorreatividade do enxerto ósseo homólogo fresco-congelado utilizado na reconstrução alveolar com finalidade de reabilitação oral com prótese sobre implantes. Anticorpos anti-HLA e anti-MICA foram monitorados através do teste Labscreen Mixed, nos intervalos 0, 7, 30, 90 e 180 pós transplante ósseo em 15 pacientes (6 homens e 9 mulheres, idade média 58,1, DP=10,1) que estavam em tratamento no Instituto de Odontologia da Pontifícia Universidade Católica do Rio de Janeiro. Caso resultado do teste Mixed fosse positivo (Razão de fundo normatizado, NBG>4,5) o teste Labscreen Single (tecnologia antígeno único por pérola, SABA) era realizado para verificar se os anticorpos anti-HLA eram específicos ao doador. Nenhum paciente relatou transplante prévio, 4 relataram transfusão prévia e todas as mulheres relataram gravidez. Dez pacientes não apresentaram reação positiva no dia 0 sendo considerados não sensibilizados previamente (NSP); destes, 6 pacientes permaneceram sem nenhuma evidência de sensibilização, 2 pacientes apresentaram reação positiva para Classe I e II; 2 para Classe I apenas; e 2 para MICA, sendo considerados sensibilizados pelo enxerto ósseo oral. Dois pacientes apresentaram aumento de Intensidade Média de Fluorescência (ΔMFI>1000) de anticorpos específicos ao doador para Classe I e Classe II, e 2 somente para Classe II, demonstrando uma reação específica ao doador. Os resultados sugerem uma alorreatividade HLA oscilatória ao enxerto ósseo homólogo em reconstruções alveolares, confirmada pela formação de anticorpos anti-HLA específicos ao doador em 4 pacientes (27%) da amostra. / Bone allografts are used without HLA donor-receptor compatibility or imunosupressor therapy. Taking in consideration the amount of bone graft procedures performed in Brazil and the possible deleterious effect of HLA sensitization in solid organ transplantation, the aim of this study was to evaluate fresh-freeze bone graft alorreactivity used in ridge augmentation surgery before oral rehabilitation with implants supported bridges. Anti-HLA and anti-MICA antibodies were evaluated by Labscreen Mixed test, at 0, 7, 30, 90 e 180 days after bone transplantation in 15 patients (6 men e 9 women, mean age 58,1, SD=10,1) treated at the Dental Institute of the Rio de Janeiro Catholic University. If the mixed test (Normalized Background Ratio, NBG>4,5) was positive, donor specificity was evaluated by Labscreen Single test (Single Antigen Bead Assay technology, SABA). None of patients had previous transplant history, 4 had transfusion history, and all women had pregnancy history. Ten patients did not have positive results at baseline and were considered not sensitized previously; 6 patients of them did not have any sensitization evidence during 6 month follow up, 2 patients had positive reaction for anti-HLA Class I and II; 2 were positive for anti-HLA Class I only; e 2 patients were positive for anti-MICA, and were considered sensitized by oral bone graft. Two patients had increased values of Median Fluorescence Intensity (ΔMFI>1000) of anti-HLA donor specific antibodies Class I and II, 2 for Class II only, showing a donor specific alorreactivity. The results sugest an oscilatory HLA reactivity, confirmed by the donor specific antibodies formation on 4 patients (27%) of this study.

Made available in DSpace on 2014-06-11T19:27:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-03-28Bitstream added on 2014-06-13T19:35:58Z : No. of bitstreams: 1 mastrantonio_ss_me_arafo.pdf: 1036636 bytes, checksum: 37dfc0cbf33459b88178c9c9a46516cb (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste trabalho foi avaliar a compatibilidade biológica in vivo de materiais odontológicos para remoção químico-mecânica do tecido cariado. Para isto, foram utilizados 32 camundongos que receberam no tecido conjuntivo subcutâneo o implante de tubos de polietileno preenchidos com Carisolv, Papacárie® e base de gel. Os animais foram sacrificados 3, 7, 20 e 30 dias após a cirurgia de implante, sendo os espécimes obtidos processados e submetidos à análise histológica. Os resultados mostraram que o Carisolv provocou uma inativação do metabolismo celular no período inicial, seguida de resposta inflamatória no período final. O grupo do Papacárie® manteve uma inflamação moderada até os 20 dias, que diminuiu de intensidade aos 30 dias e a base do gel provocou reação inflamatória discreta inicial, que aumentou aos 30 dias. Pôde-se concluir que o Carisolv, o Papacárie® e a base de gel são biocompatíveis com o tecido conjuntivo, porém as alterações provocadas por estes materiais são estatisticamente diferentes. / The aim of this work was evaluate biological compatibility in vivo of dental materials to chemo-mechanical removal of caries. This study was conducted to observe in thirty-two mice subcutaneous connective tissue reaction to the implanted polyethylene tubes filled with Carisolv, Papacárie® and gel base. The animals were sacrificed 3, 7, 20 and 30 days after the implantation procedure. The implant sites were excised and prepared for histological evaluation. The results showed that Carisolv inactivated the cellular metabolism in the initial period, followed by inflammatory response in the final period. The group of Papacárie® maintained moderate inflammation until 20 days, that reduced the intensity in 30 days and the gel base provoked initial discrete inflammatory reaction, that increased in 30 days. Carisolv, Papacárie® and gel base are biocompatible with connective tissue, although alterations caused for these materials are statistically different.