Browsing by Subject "Lymphocyte"
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Item Derivation of lymphocytes from human induced pluripotent stem cells(2014-09) Ma, ChaoHuman pluripotent stem cells have the potential to produce essentially unlimited numbers of mature and functional blood lineage populations to study human hematopoiesis. Particularly, human induced pluripotent stem cells (hiPSCs) have the advantage to provide a source of autologous transplantable blood cell populations suitable for treatment of patient specific hematological diseases. This research aims to derive human lymphocytes from hiPSCs. There are three projects: The overall generation of human lymphocytes (B cell, T cell and NK cell) from hiPSCs is explored in Project I. In Project II and III, based on the derivation of NK cells, two human immunodeficiency disease models, both caused by specific somatic gene mutation, are established using human pluripotent stem cells. The ultimate goal of this research is to use hiPSCs to study the normal development of human lymphocytes in vitro, as well as model human immunodeficiency diseases by combining with gene therapy methods, thus providing a novel approach for immunotherapy. The hypothesis is that human lymphocytes can be derived from hiPSCs and this will enable the establishment of in vitro models to study human immunodeficiency diseases. Specific aims:1. To generate human lymphocytes from hiPSCs in vitro;2. To establish two human immunodeficiency disease models (X-SCID and WAS) through in vitro derivation of lymphocytes from hESCs/hiPSCs.Item Maternal influences on neonatal immune development in pigs.(2010-08) Bandrick, Meggan MarieAdaptive immunity in the neonatal animal is primarily maternally-derived, either by immune components passing into the newborn across the placenta or following colostrum ingestion. Due to their epitheliochorial placentation, maternally-derived immunity (MDI) in swine is first transferred to the piglet in the form of colostrum. It is well established that both maternal antibodies and immune cells are transferred in colostrum and that MDI contributes to the immune repertoire of the neonate. Nonetheless, the consequences of MDI on development of neonatal immune responses, specifically cell-mediated immune (CMI) responses, warrant intense investigation, since the neonatal period is such a critical time in the animal’s life. Toward this end, the goal of this thesis was to investigate the influence of MDI on neonatal CMI responses in swine. The central hypothesis to be tested was that maternally-derived CMI is transferred to piglets, and participates in the neonatal immune response, thereby affecting neonatal immune development. In order to test the first part of this hypothesis, the cellular contribution to passive immunity and the transfer of such immunity was determined and compared to the antibody portion of colostrum. T-lymphocytes (CD4+, CD8+, and γδ) were detected in colostrum and were selectively transferred to suckling piglets. The selectivity in colostral lymphocyte transfer was in part due to genetic source since, unlike piglets allowed to suckle on their biological dams, cross-fostered piglets did not have detectable sow-derived CMI responses. To test the second part of the hypothesis, Mycoplasma hyopneumoniae (M. hyopneumoniae)-specific functional responses of lymphocytes transferred from vaccinated dams to their offspring via colostrum were evaluated. Functional activity of colostral lymphocytes was demonstrated by antigen-specific in vivo delayed type hypersensitivity (DTH) responses and in vitro lymphoproliferative responses by piglets of M. hyopneumoniae vaccinated dams but not by piglets from nonvaccinated dams. The effect of MDI on vaccine-induced antibody-mediated immune (AMI) and CMI responses M. hyopneumoniae was assessed in neonatal piglets. The potential for MDI to interfere with AMI does not extend to CMI against M. hyopneumoniae since piglets developed primary and secondary M. hyopneumoniae-specific CMI responses when vaccinated in the presence of MDI. Thus, this thesis research demonstrates a potential for MDI to affect but not interfere with neonatal CMI responses following antigen exposure. The advanced understanding of MDI gained from the studies described here will enable veterinarians and physicians to design more effective disease prevention and control strategies for neonates.