100,999 research outputs found
T cell mediated immunity in malaria and mycobacterial infection : a protective role for gd+ T cells
No full textT cell mediated immunity is essential against intracellular infections. Studies of cell mediated immunity are important for the optimal design and development of effective vaccines. Identifying correlates of protective immunity will also enable measurement of vaccine efficiency. This thesis includes studies of T cell mediated immune protection against malaria and mycobacterial infections. A major focus of this work was the investigation of the role of [gamma][delta]+ T cell responses. In an initial study of lymphocyte subset compositions, a higher percentage of cytotoxic T cells were found in the peripheral blood of healthy adults from Ethiopia and Bangladesh than from Sweden. This suggested the involvement of environmental and/or genetic factors on the adaptation of the cellular immune system.During acute malaria illness there was a complex pattern of changes in lymphocyte subset distribution and activation that appeared to be different in P. falciparum infection compared to P. vivax. During acute P. falciparum illness an increase in level and activation of [gamma][delta]+ T cells, that was mostly due to increase in V[delta]1+ cells was found. However, during both infections increased numbers of CD4+, CD8+ and [gamma][delta]+ T cells in peripheral blood were expressing the proliferation marker Ki-67. These results suggest that all T cells are activated and that lymphocyte redistribution and /or activation driven apoptosis may be the cause of the altered phenotypic profiles in peripheral blood.An in vitro assay was developed to study the functional significance of [gamma][delta]+ T cells. Generally activated [gamma][delta]+ T cells of both V[delta]1+ and V[delta]2+ subsets but not similarly activated [alpha][beta] T cells from non-malaria exposed individuals inhibited the in vitro growth of asexual blood stages of P. falciparum parasite. The inhibition was correlated to the number of [gamma][delta]+ T cells and required cell-to-cell contact. Kinetic analysis suggested the likely targets to be the late infected erythrocyte (schizonts) or extracellular merozoites. These results suggest [gamma][delta]+ T cells may have a protective role during malaria infection independent of previous exposure to malaria.An in vitro assay was also developed to measure T cell mediated inhibition of mycobacterial growth. Both [alpha][beta]+ and [gamma][delta]+ T cells from PPD positive individuals inhibited intracellular growth of BCG, but only when activated by mycobacterial antigens. The mycobacterial growth inhibition capacity was up regulated by BCG vaccination and required cell-to-cell contact. These results suggest a role for [gamma][delta]+ T cells in the memory responses against mycobacteria.Expressions of proinflammatory cytokines and cytolytic molecules such as perforin, granzymes, granulysin and Fas/Fas ligand, were characteristic of both malaria and BCG growth inhibitory T cells. However, expression of these molecules in non-inhibitory activated cells were also seen, suggesting that growth inhibition requires restricted recognition of target cells by specific effectors. Our results indicate that [gamma][delta]+ T cells may represent an important component of the primary immune defense against P. falciparum infection and the memory immune defense against mycobacterial infection.List of scientific papersI. Worku S, Christensson B, Bjorkman A, Islam D (1997). "Higher proportion of CD8+ T cells in the blood in healthy adults from Ethiopia and Bangladesh compared with Sweden" Trans R Soc Trop Med Hyg 91(5): 618-22 https://pubmed.ncbi.nlm.nih.gov/98124846II. Worku S, Bjorkman A, Troye-Blomberg M, Jemaneh L, Farnert A, Christensson B (1997). "Lymphocyte activation and subset redistribution in the peripheral blood in acute malaria illness: distinct gammadelta+ T cell patterns in Plasmodium falciparum and P. vivax infections" Clin Exp Immunol 108(1): 34-41 https://pubmed.ncbi.nlm.nih.gov/97252339III. Worku S, Troye-Blomberg M, Christensson B, Bjorkman A, Fehniger T (2000). "Activation of T cells in the blood of patients with acute malaria, Proliferative activity as indicated by Ki 67 expression" Scand J Immunol (In Print)IV. Troye-Blomberg M, Worku S, Tangteerawatana P, Jamshaid R, Soderstrom K, Elghazali G, Moretta L, Hammarstrom M, Mincheva-Nilsson L (1999). "Human gamma delta T cells that inhibit the in vitro growth of the asexual blood stages of the Plasmodium falciparum parasite express cytolytic and proinflammatory molecules" Scand J Immunol 50(6): 642-50 https://pubmed.ncbi.nlm.nih.gov/20075382V. Worku S, Hoft DF (2000). "In vitro measurement of protective mycobacterial immunity: antigen-specific expansion of T cells capable of inhibiting intracellular growth of bacille Calmette-Guerin" Clin Infect Dis Suppl 3: S257-61 https://pubmed.ncbi.nlm.nih.gov/20336492VI. Worku S, Hoft DF (2000). "Differential effects of antigen specific and control T cells on intracellular mycobacterial growth, in vitro models of protective immunity and mycobacterial persistence" (Submitted)</p
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Pelevin’s Trinity in the novel “t”: author – protagonist – reader
No full textThe article attempts to interpret Pelevin's artistic strategy in the novel "T" by exploring its subject organization and addressing the key problems of the author, the protagonist, and the reader as they are seen by the researcher. The article analyzes the peculiarities of constructing the narrative reality in the novel "T", and goes on to discuss Pelevin's philosophic models of the development of the humankind, and the emergence of his new anthropology
Measuring industry-science links through inventor-author relations: A profiling method
No full textIn this pilot study we examine the performance of text-based profiling in recovering a set of validated inventor-author links. In a first step we match patents and publications solely based on their similarity in content. Next, we compare inventor and author names on the highest ranked matches for the occurrence of name matches. Finally, we compare these candidate matches with the names listed in a validated set of inventor-author names. Our text-based profile methodology performs significantly better than a random matching of patents and publications, suggesting that text-based profiling is a valuable complementary tool to the name searches used in previous studies.innovation; industry-science links; text-based profiling;
Wave turbulence of a rotating array of quantized vortices in the T → 0 temperature limit
No full textThe dynamics of quantized vortices in the zero temperature limit is currently of great interest, particularly in the case of the Fermi superfluid He-B. Here we study wave turbulence, generated by the librating motion of a rotating cylindrical container filled with He-B, in the limit of vanishing viscous forces at temperatures . The polarization of the quantized vortices with respect to the axis of rotation is measured using non-invasive NMR techniques. We observe a decrease of the polarization when the librating motion is started, and a two-stage relaxation process when the modulation of the rotation velocity is stopped. The first relaxation process is associated with the dissipation of large-scale flow stored in inertial waves and the solid body rotation of the vortex array. From the decay of these energy reservoirs we determine the rate of energy dissipation of large-scale flow. The later second process is related to the relaxation of Kelvin waves on individual vortices. This process is monitored by the recovery of the polarization. The existence of a Kelvin wave cascade at the lowest temperatures is currently a central open question. We supply some evidence for the cascade
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
T cell mediated immunity in malaria and mycobacterial infection : a protective role for gd+ T cells [Elektronisk resurs]
No full textT cell mediated immunity is essential against intracellular infections. Studies of cell mediated immunity are important for the optimal design and development of effective vaccines. Identifying correlates of protective immunity will also enable measurement of vaccine efficiency. This thesis includes studies of T cell mediated immune protection against malaria and mycobacterial infections. A major focus of this work was the investigation of the role of [gamma][delta]+ T cell responses. In an initial study of lymphocyte subset compositions, a higher percentage of cytotoxic T cells were found in the peripheral blood of healthy adults from Ethiopia and Bangladesh than from Sweden. This suggested the involvement of environmental and/or genetic factors on the adaptation of the cellular immune system. During acute malaria illness there was a complex pattern of changes in lymphocyte subset distribution and activation that appeared to be different in P. falciparum infection compared to P. vivax. During acute P. falciparum illness an increase in level and activation of [gamma][delta]+ T cells, that was mostly due to increase in V[delta]1+ cells was found. However, during both infections increased numbers of CD4+, CD8+ and [gamma][delta]+ T cells in peripheral blood were expressing the proliferation marker Ki-67. These results suggest that all T cells are activated and that lymphocyte redistribution and /or activation driven apoptosis may be the cause of the altered phenotypic profiles in peripheral blood. An in vitro assay was developed to study the functional significance of [gamma][delta]+ T cells. Generally activated [gamma][delta]+ T cells of both V[delta]1+ and V[delta]2+ subsets but not similarly activated [alpha][beta] T cells from non-malaria exposed individuals inhibited the in vitro growth of asexual blood stages of P. falciparum parasite. The inhibition was correlated to the number of [gamma][delta]+ T cells and required cell-to-cell contact. Kinetic analysis suggested the likely targets to be the late infected erythrocyte (schizonts) or extracellular merozoites. These results suggest [gamma][delta]+ T cells may have a protective role during malaria infection independent of previous exposure to malaria. An in vitro assay was also developed to measure T cell mediated inhibition of mycobacterial growth. Both [alpha][beta]+ and [gamma][delta]+ T cells from PPD positive individuals inhibited intracellular growth of BCG, but only when activated by mycobacterial antigens. The mycobacterial growth inhibition capacity was up regulated by BCG vaccination and required cell-to-cell contact. These results suggest a role for [gamma][delta]+ T cells in the memory responses against mycobacteria. Expressions of proinflammatory cytokines and cytolytic molecules such as perforin, granzymes, granulysin and Fas/Fas ligand, were characteristic of both malaria and BCG growth inhibitory T cells. However, expression of these molecules in non-inhibitory activated cells were also seen, suggesting that growth inhibition requires restricted recognition of target cells by specific effectors. Our results indicate that [gamma][delta]+ T cells may represent an important component of the primary immune defense against P. falciparum infection and the memory immune defense against mycobacterial infection
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