44 research outputs found
Engineering at Gettysburg College
This little volume narrates the story of engineering instruction at Gettysburg College, particularly of the Engineering Department that functioned from 1912 to 1940. It includes also an account of the apparently first venture in engineering by an American liberal arts college, undertaken during the brief association of the renowned Herman Haupt with Gettysburg College between 1837 and 1847.
Time dims our memories. Although there are more than fifty living alumni who were graduated from the Engineering Department, many Gettysburgians are unaware of its existence and accomplishments. The purpose of this story is to place on record a significant aspect of our tradition. [excerpt]https://cupola.gettysburg.edu/collegehistory/1000/thumbnail.jp
Resident Memory T Cells (TRM) Are Abundant in Human Lung: Diversity, Function, and Antigen Specificity
Recent studies have shown that tissue resident memory T cells (TRM) are critical to antiviral host defense in peripheral tissues. This new appreciation of TRM that reside in epithelial tissues and mediate host defense has been studied most extensively in skin: adult human skin contains large numbers of functional TRM that express skin specific markers. Indeed, more than twice as many T cells reside in skin as in peripheral blood. This T cell population has a diverse T cell receptor repertoire, and can produce a broad array of cytokines. More recently, we have begun to examine other epithelial tissues for the presence of resident T cells. In the present study, we asked whether analogous populations of resident T cells could be found in human lung. We were able to demonstrate abundant resident T cells in human lung-more than 10 billion T cells were present. Lung T cells were largely of the effector memory T cell (TEM) phenotype, though small numbers of central memory T cells (TCM) and T regulatory cells (Treg) could be identified. Lung T cells had a diverse T cell receptor repertoire and subsets produced IL-17, IL-4, IFNΞ³, as well as TNFΞ±. A significant number of lung TRM CD4+Th cells produced more than one cytokine, identifying them as βmultifunctionalβ Th1 type cells. Finally, lung TRM, but not TRM resident to skin or T cells from blood, proliferated in response to influenza virus. This work suggests that normal human lung contains large numbers of TRM cells, and these cells are poised to respond to recall antigens previously encountered through lung mucosa. This population of T cells may contribute to the pathogenesis of asthma and other T cell mediated lung diseases
Formulation of a mmaA4 Gene Deletion Mutant of Mycobacterium bovis BCG in Cationic Liposomes Significantly Enhances Protection against Tuberculosis
A new vaccination strategy is urgently needed for improved control of the global tuberculosis (TB) epidemic. Using a mouse aerosol Mycobacterium tuberculosis challenge model, we investigated the protective efficacy of a mmaA4 gene deletion mutant of Mycobacterium bovis BCG (ΞmmaA4BCG) formulated in dimethyl dioctadecyl ammonium bromide (DDA) β D(+) trehalose 6,6 dibenenate (TDB) (DDA/TDB) adjuvant. In previous studies, deletion of the mmaA4 gene was shown to reduce the suppression of IL-12 production often seen after mycobacterial infections. While the non-adjuvanted ΞmmaA4BCG strain did not protect mice substantially better than conventional BCG against a tuberculous challenge in four protection experiments, the protective responses induced by the ΞmmaA4BCG vaccine formulated in DDA/TDB adjuvant was consistently increased relative to nonadjuvanted BCG controls. Furthermore, the ΞmmaA4BCG-DDA/TDB vaccine induced significantly higher frequencies of multifunctional (MFT) CD4 T cells expressing both IFNΞ³ and TNFΞ± (double positive) or IFNΞ³, TNFΞ± and IL-2 (triple positive) than CD4 T cells derived from mice vaccinated with BCG. These MFT cells were characterized by having higher IFNΞ³ and TNFΞ± median fluorescence intensity (MFI) values than monofunctional CD4 T cells. Interestingly, both BCG/adjuvant and ΞmmaA4BCG/adjuvant formulations induced significantly higher frequencies of CD4 T cells expressing TNFΞ± and IL-2 than nonadjuvanted BCG or ΞmmaA4BCG vaccines indicating that BCG/adjuvant mixtures may be more effective at inducing central memory T cells. Importantly, when either conventional BCG or the mutant were formulated in adjuvant and administered to SCID mice or immunocompromised mice depleted of IFNΞ³, significantly lower vaccine-derived mycobacterial CFU were detected relative to immunodeficient mice injected with non-adjuvanted BCG. Overall, these data suggest that immunization with the ΞmmaA4BCG/adjuvant formulation may be an effective, safe, and relatively inexpensive alternative to vaccination with conventional BCG
Magnitude and Complexity of Rectal Mucosa HIV-1-Specific CD8+ T-Cell Responses during Chronic Infection Reflect Clinical Status
The intestinal mucosa displays robust virus replication and pronounced CD4+ T-cell loss during acute human immunodeficiency virus type 1 (HIV-1) infection. The ability of HIV-specific CD8+ T-cells to modulate disease course has prompted intensive study, yet the significance of virus-specific CD8+ T-cells in mucosal sites remains unclear.We evaluated five distinct effector functions of HIVgag-specific CD8+ T-cells in rectal mucosa and blood, individually and in combination, in relationship to clinical status and antiretroviral therapy (ART). In subjects not on ART, the percentage of rectal Gag-specific CD8+ T-cells capable of 3, 4 or 5 simultaneous effector functions was significantly related to blood CD4 count and inversely related to plasma viral load (PVL) (p<0.05). Polyfunctional rectal CD8+ T-cells expressed higher levels of MIP-1beta and CD107a on a per cell basis than mono- or bifunctional cells. The production of TNFalpha, IFN-gamma, and CD107a by Gag-specific rectal CD8+ T-cells each correlated inversely (p<0.05) with PVL, and MIP-1beta expression revealed a similar trend. CD107a and IFN-gamma production were positively related to blood CD4 count (p<0.05), with MIP-1beta showing a similar trend. IL-2 production by rectal CD8+ T-cells was highly variable and generally low, and showed no relationship to viral load or blood CD4 count.The polyfunctionality of rectal Gag-specific CD8+ T-cells appears to be related to blood CD4 count and inversely related to PVL. The extent to which these associations reflect causality remains to be determined; nevertheless, our data suggest a potentially important role for mucosal T-cells in limiting virus replication during chronic infection
Malaria Infections Do Not Compromise Vaccine-Induced Immunity against Tuberculosis in Mice
BACKGROUND: Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis. PRINCIPAL FINDINGS: Here we show that the anti-tuberculosis protective immunity induced by four different tuberculosis vaccines was not impacted by a concurrent infection with Plasmodium yoelii NL, a nonlethal form of murine malaria. After an aerogenic challenge with virulent M. tuberculosis, the lung bacterial burdens of vaccinated animals were not statistically different in malaria infected and malaria naΓ―ve mice. Multi-parameter flow cytometric analysis showed that the frequency and the median fluorescence intensities (MFI) for specific multifunctional T (MFT) cells expressing IFN-Ξ³, TNF-Ξ±, and/or IL-2 were suppressed by the presence of malaria parasites at 2 weeks following the malaria infection but was not affected after parasite clearance at 7 and 10 weeks post-challenge with P. yoelii NL. CONCLUSIONS: Our data indicate that the effectiveness of novel TB vaccines in protecting against tuberculosis was unaffected by a primary malaria co-infection in a mouse model of pulmonary tuberculosis. While the activities of specific MFT cell subsets were reduced at elevated levels of malaria parasitemia, the T cell suppression was short-lived. Our findings have important relevance in developing strategies for the deployment of new TB vaccines in malaria endemic areas
The fossil Flora of Iowa Coal Balls: II. The Fructification of Botryopteris
Volume: 7Start Page: 157End Page: 17
PERMIAN ELEMENTS IN THE FOSSIL FLORA OF THE APPALACHIAN PROVINCE. I. TAENIOPTERIS
Volume: 3Start Page: 137End Page: 14