Immunomodulation in Dermatology
B cell-targeting therapies. T cell-targeting therapies. Anti-TNF therapies. Other pathways.
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1.4
Rebecca G. Pomerantz, Thomas S. Kupper, and Abrar A. Qureshi
Key Features
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B cell-targeting therapies T cell-targeting therapies Anti-TNF therapies Other pathways
1.4.1 Introduction The adaptive immune system mounts specific responses to defend the body from invading pathogens that have overcome the primary defense mechanisms of the nonspecific innate immune system. Lymphocytes, specialized leukocytes with surface receptors that enable recognition of a specific antigen, are the primary effector cells of the adaptive immune system. In particular, B cells (B lymphocytes) mediate the humoral immune response. Each B cell targets a single pathogen by secreting an antibody that binds to the microbe, targeting it for destruction. In contrast, cellmediated immunity involves the activation of multiple processes to destroy intracellular pathogens and lyse infected cells, in a process mediated by T cells. T cells stimulate cytokine secretion, leading to activation of destruction pathways. Immune responses are the result of the coordinated action of numerous cellular and molecular effectors.
R. G. Pomerantz () Department of Dermatology, University of Pittsburgh School of Medicine, BSTWR 1032, 3550 Terrace Street, Pittsburgh, PA 15261, USA e-mail: [email protected]
Immune dysregulation contributes to the pathogenesis of a vast array of diseases. In cancer, uncontrolled cell growth circumvents or overcomes the checks of the immune system. The goal of immune-modifying therapies for cancer is to effect antitumor responses through amplification of innate immune reactions against cancer or through delivery of tumor-specific immune effectors. In autoimmune diseases, immune cells fail to distinguish endogenous antigens from foreign antigens, leading to pathologic immune activity in which the body attacks its own tissues. Traditional therapy for autoimmune diseases is management with immunosuppressive corticosteroid agents, which block the production of inflammatory cytokines. Increasingly, highly specific immunomodulatory agents are being used to suppress particular biochemical reactions underlying autoimmune pathogenesis. B cells, T cells, and the proinflammatory cytokine TNF-a are the primary immune effectors targeted by current immunomodulatory medications for dermatologic diseases.
1.4.2 B Cell Targeting 1.4.2.1 Rituximab Rituximab is a chimeric human–murine monoclonal antibody that targets CD20, an antigen expressed by both normal and malignant B cells. By binding to CD20, rituximab reduces the number of circulating B cells in multiple pathways, including antibodydependent cellular cytotoxicity, complement-mediated cell lysis, and induction of apoptosis [1]. Because CD20 is not expressed by most plasma cells, antibody production is maintained after treatment with rituximab,
T. Krieg et al. (eds.), Therapy of Skin Diseases, DOI: 10.1007/978-3-540-78814-0_1.4, © Springer-Verlag Berlin Heidelberg 2010
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and normal B cells are later regenerated by hematopoietic stem cells. The net result is a reduction in the
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