65 research outputs found
The five dimensions of B cell tolerance
B cell tolerance has been generally understood to be an acquired property of the immune system that governs antibody specificity in ways that avoid autoâtoxicity. As useful as this understanding has proved, it fails to fully explain the existence of autoâreactive specificities in healthy individuals and contribution these may have to health. Mechanisms underlying B cell tolerance are considered to select a clonal repertoire that generates a collection of antibodies that do not bind self, ie tolerance operates more or less in three dimensions that largely spare autologous cells and antigens. Yet, most B lymphocytes in humans and probably in other vertebrates are autoâreactive and absence of these autoâreactive B cells is associated with disease. We suggest that autoâreactivity can be embodied by extending the concept of tolerance by two further dimensions, one of time and circumstance and one that allows healthy cells to actively resist injury. In this novel concept, macromolecular recognition by the B cell receptor leading to deletion, anergy, receptor editing or B cell activation is extended by taking account of the time of development of normal immune responses (4th dimension) and the accommodation (or tolerance) of normal cells to bound antibody, activation of complement, and interaction with inflammatory cells (fifth dimension). We discuss how these dimensions contribute to understanding B cell biology in health or disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153034/1/imr12813.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153034/2/imr12813_am.pd
Characterization of a New Mouse Model for Peripheral T Cell Lymphoma in Humans
Peripheral T cell lymphomas (PTCLs) are associated with a poor prognosis due to often advanced disease at the time of diagnosis and due to a lack of efficient therapeutic options. Therefore, appropriate animal models of PTCL are vital to improve clinical management of this disease. Here, we describe a monoclonal CD8+ CD4â ιβ T cell receptor Vβ2+ CD28+ T cell lymphoma line, termed T8-28. T8-28 cells were isolated from an un-manipulated adult BALB/c mouse housed under standard pathogen-free conditions. T8-28 cells induced terminal malignancy upon adoptive transfer into syngeneic BALB/c mice. Despite intracellular expression of the cytotoxic T cell differentiation marker granzyme B, T8-28 cells appeared to be defective with respect to cytotoxic activity as read-out in vitro. Among the protocols tested, only addition of interleukin 2 in vitro could partially compensate for the in vivo micro-milieu in promoting growth of the T8-28 lymphoma cells
Ethnomedicinal plant use by Lepcha tribe of Dzongu valley, bordering Khangchendzonga Biosphere Reserve, in North Sikkim, India
Is death taboo for children? Developing death ambivalence as a theoretical framework to understand children's relationship with death, dying and bereavement
Childrenâs voices are missing from debates related to the idea that death is a taboo subject and this limits understandings of how children encounter death. Drawing on data from focus groups with children aged 9â12, this paper aimed to explore if and how children experience death as a taboo, but discovered that the death-taboo thesis lacks nuance, confining and misrepresenting childrenâs experiences. Death ambivalence is thus proposed as a conceptual tool to illuminate childrenâs relationship with death. It identifies policy and practice implications concerned with developing death literacy and brings a new theorisation to death and childhood studies
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