No description available.

Mortality and decreased weight gain resulting from infection and disease in dairy calves is a problem within the dairy industry. Colostrum is the sole source of maternal immunity for the calf, having a substantial impact on health and survival. To date, colostrum quality is determined by concentration of antibodies. Colostrum also contains proteins and cells, which may enhance immune development in the neonate. Our goals were to determine the impact of colostral immune cells on (1) immune status during the first month of life and (2) immune development over time. To determine the impact of adoptively transferred colostral immune cells, calves were fed either whole colostrum (WC) or cell-free colostrum (CFC) at birth. During the first month of life, calves fed CFC had decreased numbers of CD4+ T cells when compared to WC-fed calves. However, CFC-fed calves had a greater percentage of monocytes during the first month of life. To determine the influence of colostral immune cells on immune development, cellular blood parameters were measured in response to two series of vaccinations (A and B). After vaccination series A, CFC-fed calves had decreased numbers of B cells when compared to WC-fed calves. After vaccination series B, CFC-fed calves had decreased levels of interleukin-2 gene expression and numbers of CD4+ and gamma delta T cells when compared to WC-fed calves. This study demonstrates that colostral immune cells impact immune status and development in dairy calves. / Master of Science

The roles of CD4+ and CD8+ T-cells were studied by using Cryptosporidium muris and mouse model of infection: immunized and naive BALB/c mice as a source of cells for adoptive transfer of immunity to SCID mice. Naive and primed CD4+ T-cells have a major effect in immunity of cryptosporidial infection. However SCID mice reconstituted with primed CD8+ T-cells were able to recover from the infection. The purity of the adoptive transfer pre and post-inoculation is discussed.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Thesis (Ph.D.)--Uniformed Services University of the Health Sciences, 2006 / Typescript (photocopy)

<p>We showed previously that histone deacetylase (HDAC) inhibition with MS-275 in the context of boosting oncolytic immunotherapy can drive heightened antitumor responses, leading to increased survival in mouse intracranial melanoma models. However, it is currently unclear how the co-administration of MS-275 directly impacts tumor growth. Here, we investigated the role of MS-275 in preventing the outgrowth of antigen-deficient tumor variants as a result of suboptimal treatment protocols. By adoptively transferring tumor antigen-specific memory T cells (Tm) that were expanded <em>in vivo</em> with recombinant Vesicular Stomatitis Virus (VSV-gp33), we observed complete regression of 5-day old, intradermal B16-gp33 tumors (B16-F10 overexpressing the LCMV GP33-41 epitope); however, the tumors relapsed within a month of treatment. Relapsing tumor explants were able to grow in mice that were prophylactically immunized with recombinant Adenovirus (Ad-gp33), indicating that the tumor could no longer be recognized. Strikingly however, there was zero tumor recurrence if MS-275 was co-administered with Tm and VSV-gp33, suggesting that MS-275 may prevent the emergence and/or escape of antigen loss variants. Such a benefit is lost if the administration of the drug is delayed as little as five days post VSV treatment, suggesting that its synergistic effects coincide with early immune responses and oncolytic activity. Furthermore, transplantation studies of relapsing tumor explants showed that combination treatment was unable to provide tumor protection, confirming that the mechanisms by which MS-275 prevents tumor recurrence are unlikely through direct up-regulation of antigen presentation in low- or non-antigen-expressing variants <em>in vivo</em>. Indeed, CD4 depletion in the absence of MS-275 resulted in sustained tumor regression, implying that immunoregulatory cells such as CD4+ Treg play a prominent role in sustaining tumor regression. Moreover, MS-275 modulates the phenotypic status of tumor-infiltrating MDSCs toward the differentiation of inflammatory macrophages. Taken together, the data suggests that combination therapy with HDACi with oncolytic immunotherapy mediates a synergized immune attack against the tumor through subversion of immunomodulatory mechanisms.</p> / Master of Science in Medical Sciences (MSMS)

Das Ausmaß der permanenten klinischen Defizite bei Multiple-Sklerose-Patienten entsteht durch axonale Schädigung und axonalem Verlust. In dieser Studie wird eine entscheidende Rolle des niedrigaffinen Neurotrophinrezeptors p75NTR in Bezug auf axonale Schädigung in der experimentellen autoimmunen Encephalitomyelitis (EAE) gezeigt. Nach EAE Induktion per aktiver Immunisierung mit dem Myelin-Oligodendrozyten-Glykoprotein-Peptid MOG35-55 zeigten p75NTR KO Mäuse einen verschlechterten Krankheitsverlauf, stärkere Demyelinisierung und erhöhte axonale Schädigung. Um festzustellen, ob die erhöhten Defizite von einer aggressiveren Inflammation oder von einem vulnerableren zentralen Nervensystem (ZNS) stammen, wurden das Immunsystem während der peripheren Krankheitsentstehung und der darauffolgenden Krankheitsphase und Zellen des ZNS in vivo, ex vivo und in vitro untersucht. Es wurde kein Unterschied in der Qualität der Inflammation mit Hilfe von immunohistochemischen, durchfluss-zytometrischen, ELISA- und mRNA-Analysen gefunden, wodurch eine entscheidende Rolle der untersuchten Immunzellpopulationen ausgeschlossen werden kann. Notzdestrotrotz legt die konstitutive Expression von p75NTR auf B-Zellen eine Rolle für p75NTR während der Generation der Immunantwort innerhalb der Lymphknoten nahe, da p75NTR KO Mäuse von Anfang an einen erhöhten Krankheitsverlauf zeigten. Um die Effekte der p75NTR-Defizienz während des peripheren Primings zu umgehen, wurde die EAE auch durch adoptiven Transfer eines encephalitogenen MOG35-55-spezifischen T-Zell-Klones in p75NTR KO und Wildtyp (wt) Mäusen iduziert. Sie zeigten ähnliche Inzidenz, Beginn und Kinetik der Krankheit. Ein vergleichbares Ausmaß und eine vergleichbare Qualität der Inflammation wurde mit immunohistochemischen und mRNA-Analysen in beiden Mausstämmen am Höhepunkt der Krankheit gefunden. Nichtsdestotrotz leideten p75NTR KO Mäuse an signifikant erhöhten Krankheits-Scores in der chronischen Phase infolge von erhöhtem axonalen Schaden und Verlust. Dies deutet auf eine protektive Rolle von p75NTR im ZNS hin. In dieser Arbeit wird gezeigt, dass Astrozyten, aber nicht Mikroglia, p75NTR konstitutiv exprimieren. Jedoch wurde keine p75NTR-mediierte Regulation von Cytokinen/Chemokinen und der Produktion von reaktiven Sauerstoff-Spezies in vitro gefunden. Aktive Immunisierung von Knochenmark-Chimären, in denen nur Immun- oder ZNS-Zellen einen funktionierenden p75NTR tragen, bestätigen diese Resultate. Während p75NTR KO in wt- und wt in p75NTR KO-Chimären im Vergleich zu wt in wt-Chimären unter einem stärker ausgeprägten Krankheitsverlauf am Höhepunkt der Krankheit leideten, zeigten nur wt in p75NTR KO-Tiere erhöhten axonalen Schaden und Verlust. Zusammengefaßt deuten diese Daten darauf hin, dass p75NTR-Defizienz zu einer aggressiveren peripheren Immunantwort führt (namentlich durch B-Zellen). Desweiteren hat p75NTR auch neuroprotektive Eigenschaften innerhalb des ZNS (namentlich auf Neuronen) unter experimentellen inflammatorischen Bedingungen im ZNS.