Bibliography: leaves 234-314. / 314 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the role of vascular endothelial cells in inflammation with particular reference to their participation in the immune response directed against a vascularised allograft (kidney) / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1991

Acute graft versus host disease (aGVHD) affects more than 40% of patients undergoing haematopoietic stem cell transplantation. aGVHD occurs after transplantation of donor haematopoietic cells into hosts incapable of rejecting the donor cells, when donor T cells attack host tissue. Despite extensive efforts, aGVHD remains problematic to prevent and difficult to control. Current therapies to prevent aGVHD induce profound immunosuppression, leaving patients at increased risk of infection and leukaemic relapse. Dendritic cells (DC) are professional antigen presenting cells of haematopoietic origin and are the primary stimulators of the immune system, uniquely being able to activate naïve T cells. A growing body of evidence suggests that DC are responsible for the stimulation of the donor T cells which cause aGVHD. I have used a model of aGVHD which utilizes conditioned severe combined immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMC). In this model human CD4+ T cells appear to be responsible for an aGVHD-like syndrome which results in death 15-30 days post transplant. I have shown, using in vitro depletion of individual populations, that other subpopulations of human PBMC did not affect the survival of the mice. I have also demonstrated that human DC are required for the induction of aGVHD in the majority of mice. This novel finding validated the use of this model to test the primary hypothesis; that antibody mediated depletion of DC would prevent aGVHD. The murine IgM monoclonal antibody (Mab), CMRF-44 Mab, is specific for an unknown molecule expressed on the surface of activated human DC. Previous work had shown that when mixed lymphocyte reaction stimulator cells were depleted of CMRF-44+ cells, there was a significant reduction in the proliferation of responder cells. Here I tested the efficacy of CMRF-44 as a therapy for the prevention of aGVHD in the model. CMRF-44 Mab did not improve survival of mice treated with human PBMC, despite recent data showing that CMRF-44 expression on DC was predictive of aGVHD in patients. In vitro depletion of CMRF-44+ cells from human PBMC prior to transplantation also did not reduce incidence of aGVHD. An alternate target for the depletion of human DC was CD83 which is also expressed on the surface of activated human DC. I generated a rabbit polyclonal antibody using a human CD83 fusion protein, which was then affinity purified in a multi-step process which yielded only antibody specific for human CD83. Treatment with this antibody greatly improved survival of transplanted mice. Further experiments showed that anti-CD83 treatment did not abrogate human leucocytes including CD8+ memory T cells suggesting that a therapy using an anti-CD83 antibody has the potential to prevent aGVHD without the immunosuppression associated with current anti-aGVHD therapies. The work described here has validated the use of a human mouse chimeric model as an in vivo assay of human DC function and shown that targeting CD83 has the potential to reduce the incidence of clinical aGVHD whilst preserving donor memory T cells.

Thesis (M.S.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed June 2, 2008). Includes bibliographical references (p. 33-42).

Thesis (PhD.(Anatomy)--Faculty of Health Sciences)-University of Pretoria, 2007. / Includes bibliographical references.

Thesis (Ph.D. in Cancer Biology) -- University of Colorado at Denver and Health Sciences Center, 2006. / Typescript. Includes bibliographical references (leaves 136-169). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Fundação de Amparo a Pesquisa do Estado de Minas Gerais / The nematode Strongyloides stercoralis responsible for strongyloidiasis diagnosed by detection of larvae in feces. However, the elimination of low larvae hampers the detection of disease particularly in cases of immunosuppression. Immunodiagnostic tests have been developed, but the difficulty of obtaining larvae of S. stercoralis for the production of homologous antigenic extract, thereby Strongyloides venezuelensis and their different evolutionary forms for the production of antigen extracts. The aim of this study was to evaluate the detection of antibodies anti S. venezuelensis against alkaline extracts of L3 larvae, parthenogenetic females or eggs in experimental strongyloidiasis associated with immunosuppression. Male rats were divided into two groups: non-immunosuppressed and immunosuppressed experimentally infected and serum from all animals were obtained at 0, 5th, 8th, 13th and 21th days post infection (d.p.i.). The test enzyme-linked immunosorbent assay (ELISA) was performed to compare the reactive potential of alkaline extracts of L3 larvae, parthenogenetic females and eggs of S. venezuelensis in rats non-immunosuppressed and immunosuppressed. Immunoblotting was also evaluated for detection of IgG anti S. venezuelensis in both groups front to alkaline of the three developmental forms of the parasite extracts. In all comparative ELISA extracts were skilled in detecting IgG S. venezuelensis. The extract of larvae showed reactivity from the 5th dpi ceasing at 21th d.p.i in the non-immunosuppressed group while the group immunosuppressed this reactivity remained at 21th d.p.i. immunoblotting showed the reactivity profile with immunoreactive fractions in immunosuppressed group from the 5th d.p.i. while the non-immunosuppressed group reactivity from 8th d.p.i. The alkali extracts of parthenogenetic females and eggs showed a similar profile of reactivity in both ELISA and immunoblotting. Immunoreactive protein fractions of 26 and 17 kDa present in the alkaline extract of larvae presented as important markers of infection in immunosuppressed animals. It is concluded that all alkali extracts have diagnostic potential in experimental strongyloidiasis especially the larval extract in cases of immunosuppression, and immunoblotting an important complementary diagnostic tool. / O nematódeo Strongyloides stercoralis é responsável pela estrongiloidíase cujo diagnóstico é realizado pela detecção de larvas nas fezes. Porém a baixa eliminação de larvas dificulta a detecção da doença em especial em casos de imunossupressão. Testes imunodiagnósticos têm sido desenvolvidos, porém há dificuldade de se obter larvas de S. stercoralis para a produção de extrato antigênico homólogo assim o parasito Strongyloides venezuelensis e suas diferentes formas evolutivas são utilizados para produção de extratos antigênicos. O objetivo do presente estudo foi avaliar a detecção de anticorpos anti S. venezuelensis a partir de extratos alcalinos de larvas L3, fêmeas partenogenéticas ou ovos na estrongiloidíase experimental associada à imunossupressão. Ratos machos foram divididos em dois grupos: não-imunossuprimidos e imunossuprimidos experimentalmente infectados e o soro de todos os animais foram obtidos no 0, 5º, 8º, 13º e 21º dias pós-infecção (d.p.i.). O teste enzyme-linked immunosorbent assay (ELISA) foi realizado para comparar o potencial reativo dos extratos alcalinos de larva L3, fêmeas partenogenéticas e ovos de S. venezuelensis em ratos não-imunossuprimidos e imunossuprimido. Immunoblotting foi avaliado quanto sua detecção de IgG anti S. venezuelensis em ambos os grupos frente aos extratos alcalinos das três formas evolutivas do parasito. No ELISA comparativo todos extratos foram efetivos na detecção de anti-IgG de S. venezuelensis. O extrato de larvas apresentou reatividade a partir do 5º d.p.i cessando no 21º d.p.i. no grupo não-imunossuprimido enquanto o grupo imunossuprimido essa reatividade permaneceu no 21º d.p.i.. O immunoblotting apresentou perfil de reatividade com frações imunorreativas no grupo imunossuprimido a partir do 5º d.p.i. enquanto o grupo não-imunossuprimido a reatividade a partir do 8º d.p.i. Os extratos alcalinos de fêmeas partenogenéticas e de ovos apresentaram similar perfil de reatividade tanto no ELISA comparativo quanto no immunoblotting. Frações proteicas imunorreativas de 26 e 17 kDa presentes no extrato alcalino de larvas apresentaram como importantes marcadores de infecção em animais imunossuprimidos. Conclui-se que todos os extratos alcalinos possuem potencial diagnóstico na estrongiloidíase experimental com destaque para o extrato de larvas em casos de imunossupressão, sendo o immunoblotting uma importante ferramenta diagnóstica complementar. / Mestre em Imunologia e Parasitologia Aplicadas

Made available in DSpace on 2015-05-14T12:56:07Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1184583 bytes, checksum: e7d5f827d1dea31a7b5d11cc69a3c72d (MD5) Previous issue date: 2009-12-11 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of the present study was to assess the oral health status of children infected with HIV virus. A prospective, observational, descriptive, case-control study was carried out in the city of João Pessoa, PB, Brazil. The sample consisted of a study group (SG) made up of 21 children infected with HIV in treatment at the Infectology Unit of the Clementino Fraga Hospital Complex and a control group (CG) of 28 children with no history of HIV infection covered by the Jardim Miramar II Family Health Program. Dental caries indices, (DMFT and deft), gingival status indices (VPI, GBA, OHI-S), resting and stimulated salivary flow and salivary buffer capacity were determined. The deft index was 3.19 ± 3.21(95%CI 1.73-4.66) in the SG and 2.54 ± 1.9 (95%CI 1.78-3.29) in the CG; the DMFT was 3.52 ± 2.6 (95%CI 2.34-4.71) in the SG and 1.32 ± 1.4 (95%CI 0.74-1.90) in the CG (p=0.002). There were statistically significant differences between groups in the decayed component for both the primary (p=0.02) and permanent (p<0.0001) dentition as well as in the filled component for the primary dentition (p<0.0001). The presence of visible biofilm was 52.9% in the SG and 47.1% in the CG (p=0.031). Gingivitis, measured by the gingival bleeding index (GBI) was absent in 57.1% of the SG and 78.5% of the CG (p=0.09). There was a difference between groups in resting saliva flow (p=0.01). There was a high frequency of caries in the SG. The most prevalent need for treatment in the SG was extraction, whereas the most prevalent treatment need in the CG was for procedures of low complexity. The organization of services is suggested for addressing this clinical demand and a health promotion program should be implemented for this population. / Este estudo teve como objetivo avaliar as condições de saúde bucal de crianças infectadas ou não pelo vírus HIV. A amostra foi composta por um grupo de estudo (GE), constituído por 21 crianças infectadas pelo HIV, atendidas no setor de infectologia do Complexo Hospitalar Clementino Fraga e por um grupo controle (GC) de 28 crianças sem história de infecção pelo HIV, atendidas no Programa de Saúde da Família Jardim Miramar II. A pesquisa é do tipo descritiva, observacional, prospectiva, e do tipo caso-controle, e foi desenvolvido em João Pessoa, PB, Brasil. Em ambos os grupos foram determinados o índice de cárie dentária (ceo-d e CPO-D), índices da condição gengival (IPV, ISG, IHO-S), além do fluxo salivar em repouso e o estimulado, e a capacidade tampão da saliva. A análise estatística foi feita através de testes de associação, como o Qui-quadrado e Exato de Fisher, além do teste de Mann-Whitney; todos com nível de significância de 95% (p<0,05). Observou-se ceo-d de 3,19 ± 3,21(IC95% 1,73 - 4,66) GE e 2,54 ± 1,9 (IC95% 1,78- 3,29) GC, já o CPO-D foi de 3,52 ± 2,6 (IC 95% 2,34 - 4,71) GE e 1,32 ± 1,4 (IC95% 0,74 - 1,90) GC (p=0,002). Em relação aos componentes verificou-se diferença estatística para o componente c cariado tanto na dentição decídua (p=0,02) como na permanente (p<0,0001) e para o componente O obturado na dentição decídua (p<0,0001). Observou-se presença de biofilme visível em 52,9% (GE) e 47,1% (GC) (p=0,031). A ausência de gengivite pelo índice de Sangramento Gengival (ISG) foi de 57,1% (GE) e 78,5% (GC) (p=0,09). Observou-se diferença entre os grupos para o fluxo salivar em repouso (p=0,01). Verificou-se alto índice de cárie nas crianças do GE. A necessidade de tratamento mais prevalente foi a extração (GE), enquanto que para o GC foi de procedimentos de baixa complexidade. As condições da saúde bucal das crianças com HIV não foram satisfatórias quando comparadas às do GC.

Objective: The survival rates for cardiac arrest patients to hospital discharge are very low. Post-arrest patients have an immune response and usually a period of immunosuppression. When CD3+ T cells activate, they switch from primarily relying on aerobic metabolism to primarily relying on anaerobic metabolism. The goal of this study is to characterize the immune system of post-cardiac arrest patients. The specific objectives are (1) to determine the time period after the occurrence of a cardiac arrest that a patient acquires an infection, (2) to identify the most common types of infections in post-arrest patients, (3) to compare in vitro the cellular oxygen consumption of immune cells post-cardiac arrest with healthy controls, and (4) to compare cell proliferation and ATP production of immune cells post-cardiac arrest with healthy controls. Methods: We conducted a retrospective chart review of 170 cardiac arrest patients (Beth Israel Deaconess Medical Center) who had return of spontaneous circulation. We measured oxygen consumption rates of peripheral blood mononuclear cells (PBMCs) in cardiac arrest patients and healthy controls. We also measured cell proliferation and ATP production of CD3+ T cells in cardiac arrest patients and healthy controls. Results: Of the 170 cardiac arrest patients we reviewed, 42% had at least one incidence of infection. The length of time from cardiac arrest to first positive culture was 4 days, with pneumonia and urinary tract infections the most common diagnoses. The PBMCs of cardiac arrest patients showed a significant decrease in oxygen consumption post arrest compared with healthy controls. When thiamine was added to the PBMC samples of cardiac arrest patients, there was a significant increase in oxygen consumption from baseline. There was no significant difference in cell proliferation or ATP production of CD3+ T cells between the two groups of post-cardiac arrest patients and healthy controls. Conclusion: Many patients suffer from infections post-cardiac arrest, and future research is needed on this subject. Our data support the hypothesis that post-arrest patients have a period of hyperimmune response followed by a period of immunosuppression.

Chronic immune insult and immunosuppressant-related toxicities have remained an enduring challenge in organ transplantation. Long-term survival of transplant patients has improved marginally in recent decades due to these challenges. To circumvent these issues, transplant investigators have researched immune tolerance mechanisms that demonstrate potential to induce immunosuppression and rejection-free survival in the clinic. One mechanism in particular, the liver tolerance effect, has already demonstrated this experimentally and clinically. Liver transplants in experimental models and human patients have exhibited the ability to become spontaneously accepted without being rejected by the recipient’s immune system. Research in recent decades has revealed that the liver parenchymal and non-parenchymal cell populations harbor potent immunomodulatory properties. In the context of liver transplantation, it has been found that two cell populations in particular, the mesenchyme-derived liver sinusoidal endothelial cells and hepatic stellate cells, mediate the induction of liver transplant tolerance through a mechanism known as mesenchyme-mediated immune control.

Masters of Science / Background: Infection with HIV results in gradual loss of immunologic functions, especially those mediated by CD4+T helper cells with consequent impairment of the immune response leading to severe manifestations of periodontal disease. The lower the CD4+T lymphocyte cell count or the higher the level of immunosuppression, the higher the incidence of periodontal disease in those patients will be. Putative periodontopathic bacteria namely Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, commonly referred to as "red complex", and many other bacterial species have been implicated in the initiation and progression of periodontal disease. Objective: The present study tests the association between different CD4+T lymphocyte levels and "red complex" pathogens using BANA, in HIV-positive patients with chronic inflammatory periodontal disease (CIPD). Methods: 120 HIV-positive patients from the infectious disease clinic at Tygerberg hospital participated in the study with a mean age of 33.3 years. The CD4+T lymphocyte counts were obtained from patient's medical records. The six Ramjford teeth were used for evaluating periodontal clinical parameters such as plaque index, gingival index, periodontal probing depth and clinical attachment loss. Subgingival plaque samples were collected and analyzed by the enzymatic BANA test for the detection of the "red complex". Results: The CD4+T lymphocyte mean level was 293.43cells/mm3. Statistically significant associations were found between CD4+T cell counts and probing depth (p= 0.0434) and clinical attachment loss (p= 0.0268). Significant associations were found between BANA with all the clinical indices (p= <0.05). However no association was found between CD4+T cell counts and BANA. Conclusion: HIV-positive patients show a high prevalence of "red complex" pathogens subgingivally. Immunosuppression seems to favour the colonization of these species, resulting in periodontal disease manifestations.