100 research outputs found
ICAMs support B cell interactions with T follicular helper cells and promote clonal selection.
The germinal center (GC) reaction begins with a diverse and expanded group of B cell clones bearing a wide range of antibody affinities. During GC colonization, B cells engage in long-lasting interactions with T follicular helper (Tfh) cells, a process that depends on antigen uptake and antigen presentation to the Tfh cells. How long-lasting T-B interactions and B cell clonal expansion are regulated by antigen presentation remains unclear. Here, we use in vivo B cell competition models and intravital imaging to examine the adhesive mechanisms governing B cell selection for GC colonization. We find that intercellular adhesion molecule 1 (ICAM-1) and ICAM-2 on B cells are essential for long-lasting cognate Tfh-B cell interactions and efficient selection of low-affinity B cell clones for proliferative clonal expansion. Thus, B cell ICAMs promote efficient antibody immune response by enhancement of T cell help to cognate B cells
Millbank tendency: the strengths and limitations of mediated protest ‘events’ in UK student activism cycles
UK students’ desire to create disruptive, media-friendly ‘events’ during the 2010-11 protests against fees and cuts is reflective of wider cycles and processes in student activism history. First, constant cohort turnover restricts students’ ability to convert campaigns into durable movements, necessitating that they must periodically ‘start from scratch’. This informs a second process, namely the need to gain the attention of mainstream media, as this can potentially amplify students’ grievances far beyond their own organisational capacities. Both have shaped student activism over the past fifty years, compelling contemporary students to create protest events that live up to their radical history. These processes were evident in autumn 2010, when an NUS demonstration saw students attack and briefly occupy Conservative Party headquarters at 30 Millbank. The protest’s mass mediation was central to activists’ ‘eventing’ processes, and provided the spark for the radical UK-wide campaign that followed. Yet once the fees bill was passed by Parliament, students’ dependency on mainstream media cycles was quickly exposed. With ‘mediatization’ tendencies having dogged student activism since the sixties, this article argues that creating ‘events’ epitomises students’ longstanding strengths and limitations as society’s ‘incipient intelligentsia’ (Rootes, 1980: 475)
Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice
A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens
A dynamic T cell–limited checkpoint regulates affinity-dependent B cell entry into the germinal center
Entry into the germinal center requires antigen-bearing B cells to compete for cognate T cell help at the T–B border
HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice
Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1–infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, lowering the initial viral load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn. Similarly, a single injection of adeno-associated virus directing expression of one bNAb produced durable viremic control after ART was terminated. We conclude that immunotherapy reduces plasma viral load and cell-associated HIV-1 DNA and that decreasing the initial viral load enables single bNAbs to control viremia in hu-mice
See-through abdomen display for minimally invasive surgery
This invention is in the domain of minimally invasive surgery and is a method and apparatus that transforms and displays images of internal organs and tissues taken from internally located imaging devices on external skin. The image displayed on the skin aligns with the actual physical location, orientation, and size of the internal organs and tissues in a way that viewers have the perception that the skin is transparent. This method and apparatus enables surgeons to have the same hand-eye coordination as in an open surgery during a minimally invasive surgery
Virtually Transparent Epidermal Imagery for Laparo-Endoscopic Single-Site Surgery
This paper presents a novel design, and prototype implementation, of a virtually transparent epidermal imagery (VTEI) system for laparo-endoscopic single-site (LESS) surgery. The system uses a network of multiple, micro wireless cameras and multiview mosaicing technique to obtain a panoramic view of the surgery area. This view provides visual feedback to surgeons with large viewing angles and areas of interest so that the surgeons can improve the safety of surgical procedures by being better aware of where the surgical instruments are relative to tissue and organs. The prototype VTEI system also projects the generated panoramic view on the abdomen area to create a transparent display effect that mimics equivalent, but higher risk, open-cavity surgeries
Minimally invasive surgery platform attachment apparatus
An apparatus for the insertion, placement, attachment, and removal of a surgical device includes a handle and an elongate shaft. Opposing spring fingers that open and close relative to one another are partially and slidably disposed within the distal end of the elongate shaft opposite the handle. The opposing spring fingers are adapted to grasp a surgical device and power the surgical device via physical conductors on the spring fingers or graspers attached thereto, resulting in the surgical device being fully functional. A first trigger mechanism opens and closes the spring fingers via a piston disposed within the elongate shaft. A second trigger mechanism rotates the surgical device grasped by the spring fingers
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