Thesis (Ph. D.)--University of Virginia, 2001. / Spine title: Yersinia uptake by mammalian cells. Includes bibliographical references (leaves 214-240). Also available online through Digital Dissertations.

Thesis: M.S., Massachusetts Institute of Technology, Department of Nutrition and Food Science, 1980 / Bibliography: leaves 56-57. / by Julianne Elizabeth Radkowski Opperman. / M.S. / M.S. Massachusetts Institute of Technology, Department of Nutrition and Food Science

Dendritic cells (DCs) comprise a distinct lineage of potent antigen-presenting mononuclear phagocytes that serve as both mediators of innate immune responses and key facilitators of the adaptive immune response. DCs play both immunogenic and tolerogenic roles through their dual ability to elicit pathogen-specific T cell immunity as well as induce regulatory T cell (Treg) responses to promote tolerance in the steady state. The aim of the work presented here is to examine the normal regulatory mechanisms of DC development and function, starting with the dissection of mechanisms behind an aberrantly activated developmental pathway, followed by the exploration of new mechanisms governed by two candidate transcription factors. The first chapter of the thesis focuses on the growth factor receptor Flt3, an essential regulator of normal DC development in both mice and humans, and concurrently one of the most commonly mutated proteins found in acute myeloid leukemia (AML). We investigated the effect of its most common activating mutation in AML, the Flt3 internal tandem duplication (Flt3-ITD), and found that this mutation caused a significant cell-intrinsic expansion of all DC populations. This effect was associated with an expansion of Tregs and the ability to dampen self-reactivity, with an inability to control autoimmunity in the absence of Tregs. Thus, we describe a potential mechanism by which leukemia can modulate T cell responses and support Treg expansion indirectly through DCs, which may compromise immunosurveillance and promote leukemogenesis. The subsequent chapters explore the basic molecular mechanisms of DC development by using Flt3 expression as a guide to uncover new candidates involved in the DC transcriptional program. We show that Myc family transcription factor, Mycl1, is largely dispensable for DC development and function, contrary to recent published findings that propose a role in proliferation and T cell priming. On the other hand, we find that conditional deletion of our second candidate gene, an Ets family transcription factor, has diverse effects on DC development, monocyte homeostasis, and cytokine production. Overall, our studies highlight an unexpected molecular link between DC development and leukemogenesis, and elucidate novel mechanisms controlling DC differentiation and function.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on December 12, 2007) Vita. Includes bibliographical references.

The location of the immunologic response to an allograft is not known with certainty. However, organized collections of T cells, B cells and antigen presenting cells have been found in peripheral tissue, in close proximity to organs undergoing rejection. It is hypothesized that this tertiary lymphoid tissue may be a location in which activation of lymphocytes can occur, leading to rejection of an allograft. We report here that in a splenectomized aly/aly mouse, which is devoid of secondary lymphoid organs and will normally fail to reject an allograft, the presence of tertiary lymphoid organs is associated with graft rejection. We additionally find that tertiary lymphoid organs can act as lymph nodes, and can support effector and memory allograft rejection responses. It is demonstrated that ectopic lymphoid tissue in aly/aly mice will support the multiplication and transformation of transferred naïve CD4 and CD8 T cells into cells that display phenotypic markers characteristic of effector and memory lymphocytes. These results demonstrate that ectopic lymphoid tissue is associated with the loss of immunologic ignorance and is sufficient to enable graft rejection. This suggests that allograft rejection may take place within ectopic lymphoid tissue, and suggests that techniques to interfere with the development of this tissue might offer a therapeutic approach to preserving organ allografts.

Disputats, Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser. Med populärvetenskaplig sammanfattning på svenska.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Orientador: Albina Messias de Almeida Milani Altemani / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T12:03:45Z (GMT). No. of bitstreams: 1 Barreto_IcleiaSiqueira_D.pdf: 12646702 bytes, checksum: 9cc75301ed45a05b163a8e355ac78a7e (MD5) Previous issue date: 2010 / Resumo: Pólipos tonsilares são lesões não neoplásicas usualmente constituídas por quantidades variáveis de tecidos linfóide, vascular e conjuntivo. Todos são considerados como proliferações hamartomatosas, mas o perfil dos componentes vascular e conjuntivo, necessita de estudo mais aprofundado. O sistema vascular das tonsilas é complexo e inclui estruturas altamente especializadas (Vênulas do Endotélio Alto- VEA), envolvidas no tráfico dos linfócitos para os tecidos linfóides. Foram estudados 14 pólipos tonsilares e 26 tonsilas palatinas, usando CD34 (para vasos sanguíneos e VEA), CD105 (para VEA), D2-40 (para vasos linfáticos), Ki-67 (para índice proliferativo), colágenos I e III, fibronectina e tenascina-C (para proteínas da matriz extracelular). Os pólipos mostraram aumento significante da área linfática total, enquanto o número de vasos (sanguíneos e linfáticos) e a área vascular sanguínea não diferiram significativamente das tonsilas controles. Raras células endoteliais expressaram Ki-67. Nos pólipos, pela primeira vez foi demonstrada a presença de VEAs, as quais foram identificadas em meio ao tecido linfóide. A quantidade deste último correlacionou-se positivamente com a densidade destas estruturas. Os pólipos também apresentaram menor quantidade de fibronectina e colágenos I e III, os quais estavam distribuídos de forma desorganizada. A expressão de tenascina-C foi pouco frequente nos pólipos e nas tonsilas controles. Concluindo, os pólipos tonsilares são compostos por tecido conjuntivo desorganizado e canais linfáticos dilatados, que podem ser consideradas proliferações hamartomatosas. Todavia, o componente linfóide possivelmente é reacional, devido a sua relação com as VEA. O fenótipo altamente diferenciado das VEAs e sua biologia complexa não são condizentes com natureza hamartomatosa / Abstract: Tonsillar polyps are nonneoplastic lesions usually composed of a variable amounts of lymphoid, vascular and connective tissues. All are generally assumed to be hamartomatous proliferations but the profile of vascular and connective components has yet to be explored. The vascular system of the tonsils is complex and includes highly specialized structures (i.e. high endothelial venules -HEVs) involved in lymphocyte homing into lymphoid tissues. In 14 tonsillar polyps and 26 control tonsils an immunohistochemical study was performed using CD34 (for blood vessels and HEVs), CD105 (for HEVs), D2-40 (for lymphatic vessels), Ki-67 (for proliferating index), collagens I and III, fibronectin and tenascin-C (for proteins of the extracellular matrix). The polyps showed increased total lymphatic area, whereas number of vessels (sanguineous and lymphatic) and blood vascular area did not differ significantly from those of control tonsils. Rare Ki-67+ endothelial cells were found. In the polyps, HEV was encountered amid lymphoid tissue and its amount correlated positively with the HEV density. The polyps also presented lesser amounts of fibronectin and collagens I and III which were distributed in a disorganized fashion. Tenascin-C expression was uncommon in the polyps and control tonsils. In conclusion, the tonsillar polyps are composed of disorganized connective tissue and lymphatic channels which can be considered hamartomatous proliferations. However, the lymphoid component is possibly reactive due to its relationship with the HEVs. The highly differentiated phenotype of the HEVs and its complex biology are not in agreement with what would be expected for a component of hamartomatous nature / Doutorado / Anatomia Patologica / Doutor em Ciências Médicas