2 results
88 - Biologics
- from Part XI - The susceptible host
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- By Pritha Sen, Massachusetts General Hospital, Jatin M. Vyas, Massachusetts General Hospital
- Edited by David Schlossberg, Temple University, Philadelphia
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- Book:
- Clinical Infectious Disease
- Published online:
- 05 April 2015
- Print publication:
- 23 April 2015, pp 567-572
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- Chapter
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Summary
Introduction
Biologic therapies have revolutionized nearly every discipline of medicine. As our understanding of the relevant immunologic pathways of cancer, rheumatologic disease, hematopoietic and solid organ transplantation has evolved, so has the discovery of new monoclonal antibodies for targeted therapy. Currently, over 100 monoclonal antibodies have been approved for clinical use. This chapter highlights two commonly used monoclonal antibodies and their associated infectious complications. We outline the immunologic mechanism of action and indications of use of these important biologic therapies. We also examine the commonly reported infectious complications and summarize the role for pre-implementation diagnostics, post-implementation surveillance, and antimicrobial prophylaxis.
Lymphocyte-depleting therapies
Monoclonal antibodies that target surface proteins found on lymphocytes including alemtuzumab (humanized chimeric monoclonal antibody that recognizes CD52) and rituximab (chimeric murine/human monoclonal antibody directed against the CD20) have been used successfully in the management of lymphoproliferative disorders and autoimmune diseases. We focus on rituximab because of the propensity of available data. Rituximab is constructed with human IgG1 and kappa-chain constant regions and heavy and light chain variable regions from a murine antibody to the CD20 antigen, a hydrophobic transmembrane protein which is present on mature B lymphocytes but absent from the surface of normal plasma cells. Rituximab eliminates mature B cells. Although the CD20 antigen is absent from the surface of mature plasma cells, rituximab can be complicated by hypogammaglobulinemia; the precise mechanism is incompletely understood. Rituximab is currently approved for the treatment of non-Hodgkin's lymphoma (NHL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. In addition, rituximab is approved as second-line therapy for rheumatoid arthritis (RA) not responsive to tumor necrosis factor (TNF)-blocking agents. This anti-CD20 monoclonal antibody has also been widely used off-label for lupus, autoimmune hematologic diseases (including primary idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia), multiple sclerosis, bullous dermatologic disorders, immune-mediated glomerular disease, and cryoglobulinemia.
62 - Herpesvirus evasion of T-cell immunity
- from Part V - Subversion of adaptive immunity
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- By Benjamin E. Gewurz, Department of Pathology, Harvard Medical School, Boston, MA, USA, Jatin M. Vyas, Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA, Hidde L. Ploegh, Department of Pathology, Harvard Medical School, Boston, MA, USA
- Edited by Ann Arvin, Stanford University, California, Gabriella Campadelli-Fiume, Università degli Studi, Bologna, Italy, Edward Mocarski, Emory University, Atlanta, Patrick S. Moore, University of Pittsburgh, Bernard Roizman, University of Chicago, Richard Whitley, University of Alabama, Birmingham, Koichi Yamanishi, University of Osaka, Japan
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- Book:
- Human Herpesviruses
- Published online:
- 24 December 2009
- Print publication:
- 16 August 2007, pp 1117-1136
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- Chapter
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Summary
The multiple layers of the human immune response present a challenge to viruses, which must survive and multiply within a host for a sufficient period of time to allow successful transmission to susceptible individuals. Given the large proteomes and comparatively low polymerase error rate of human herpesviruses, antiviral immunity at first glance appear to have the upper hand. Nonetheless, herpesviruses manage prolonged incubation periods following initial infection, with systemic dissemination and prolonged secretion, often from multiple sites. In contrast to the similarly large poxviruses, the ability to subsequently establish persistent infection is a hallmark of the human herpesviruses. To enable this lifestyle, the herpesviruses devote a significant proportion of their genome coding capacity to the expression of immuno-evasins, a collection of molecules that disrupt normal immune physiology. Each human herpesvirus studied has evolved elegant cell biological solutions to problems posed by the immune response.
Innate immunity, an evolutionarily conserved and relatively non-specific system of pattern recognition molecules hardwired in the genome, cytokines such as interferons, phagocytes and natural killer (NK) cells, represents the first line deployed against microbial invaders, including herpesviruses (Janeway and Medzhitov, 2002). The clonal expansion of B- and T- lymphocytes that bear antigen-specific receptors for viral epitopes underlies the adaptive antiviral immune response, laying the groundwork for a highly pathogen-specific defense. Such specificity comes at a price – lymphocyte proliferation requires time to unfold, and innate immunity, in particular NK-cell activity, limits the initial herpesvirus spread.