926 resultados para live-looping
Resumo:
Vaccination with live Leishmania major has been shown to yield effective immunization in humans; however, this has been discontinued because of problems associated with virulence of the available vaccine lines. To circumvent this, we tested the ability of a dhfr-ts- null mutant of L. major, obtained by gene targeting, to infect and then to vaccinate mice against challenge with virulent L. major. Survival and replication of dhfr-ts- in macrophages in vitro were dependent upon thymidine, with parasites differentiating into amastigotes prior to destruction. dhfr-ts- parasites persisted in BALB/c mice for up to 2 months, declining with a half-life of 2-3 days. Nonetheless, dhfr-ts- was incapable of causing disease in both susceptible and immunodeficient (nu/nu) BALB/c mice. Animal infectivity could be partially restored by thymidine supplementation. When inoculated by the i.v., s.c., or i.m. routes into mice, dhfr-ts- could elicit substantial resistance to a subsequent challenge with virulent L. major. Thus, Leishmania bearing auxotrophic gene knockouts can be safe and induce protective immunity. Potentially, dhfr-ts- could be used as a platform for delivery of immunogens relevant to other diseases.
Resumo:
Listeria monocytogenes (LM) is a Gram-positive bacterium that is able to enter host cells, escape from the endocytic vesicle, multiply within the cytoplasm, and spread directly from cell to cell without encountering the extracellular milieu. The ability of LM to gain access to the host cell cytosol allows proteins secreted by the bacterium to efficiently enter the pathway for major histocompatibility complex class I antigen processing and presentation. We have established a genetic system for expression and secretion of foreign antigens by recombinant strains, based on stable site-specific integration of expression cassettes into the LM genome. The ability of LM recombinants to induce protective immunity against a heterologous pathogen was demonstrated with lymphocytic choriomeningitis virus (LCMV). LM strains expressing the entire LCMV nucleoprotein or an H-2Ld-restricted nucleoprotein epitope (aa 118-126) were constructed. Immunization of mice with LM vaccine strains conferred protection against challenge with virulent strains of LCMV that otherwise establish chronic infection in naive adult mice. In vivo depletion of CD8+ T cells from vaccinated mice abrogated their ability to clear viral infection, showing that protective anti-viral immunity was due to CD8+ T cells.
Resumo:
This study, using the portraiture methodology, provides an analysis of the lifelong significance of an undergraduate program that integrates literature with an outdoor experiential platform. With limited research on long-term effects of an academic outdoor experiential course on one's life, there is space to wonder about the prospect and nature of the long-term significance of an academic course that may offer technical skill, intrapersonal and interpersonal development, and also the delivery of subject matter related to a traditional or mainstream academic area of study. Utilizing an academic skills-oriented lens as well as a character strengths lens, portraits were crafted of four former participants of the University of Michigan's New England Literature Program (NELP) to shed light on the long-term influence of this type of course, crucial participant characteristics that contribute to the program's impact, and specific components of the program that are particularly integral to the course's efficacy. Since 1975, each spring term a small contingent of students and educators has lived in the woods in the New England region as a community of learners, artists and explorers. NELP is an exemplar of a longstanding undergraduate academic English course that integrates the literature of New England writers, exploratory writing and student experiences relating to regional literature and the land. Emergent themes of this course's long-term influence on former participants include increased collaborative skills, increased self-confidence and self-knowledge, a reinforcement of lifelong relationships with the outdoors, and nurtured creativity. For participants to reap benefit from this course, it was important for them to enter with maturity to conduct themselves with openness to new experiences, relationships, and extensive reflection. Findings relating to the integral components of such a program include that of being place-based, oriented towards process, and being an intentional, collaborative community.
Resumo:
No abstract.
