Natural autoantibodies are defined as self-reactive antibodies present in healthy individuals in the absence of purposeful immunization or any known antigenic stimulation. While most NAAbs are of the IgM isotype, T cell dependent isotypes such as IgG and IgA NAAbs have been reported. Natural antibodies are conserved through evolution; they have been detected in sharks and humans, the phylogenetic limits of vertebrates capable of producing antibodies. The phylogenetic conservation of NAAbs suggests that they play an important, but overlooked, role in the maintenance of physiological homeostasis of the immune system. My project involved the characterization of two NAAbs. The first part of my dissertation elucidates the production and functional characterization of an anti-T Cell Receptor NAAb, OR3. OR3 is an IgM heterohybridoma made from the peripheral blood B cells of a patient with Rheumatoid Arthritis. The results show that OR3 specifically binds to the Complementarity Determining Region 1 segment of TCRV b8 regions, is specific for a subset of T cells and blocks the antigen activation of these T cells. Importantly, OR3 does not induce apoptosis or necrosis of T cells. My results support our hypothesis that anti-TCR NAAbs are immunomodulatory and indicate that autoantibodies present in humans may have significant functional activity in the regulation of T cell responses. The second part of the dissertation describes the phenomenon of NAAbs to human delta opioid receptor. I affinity purified IgG antibodies to human DOR from intravenous immunoglobulin, a therapeutic blood product that contains purified IgG isolated from the plasma of thousands of healthy donors. The anti-DOR NAAbs bind to DOR protein, and initiate an activating signaling cascade, in a manner similar to a receptor specific agonist. Interestingly, there is a significant difference in the agonistic activity of the autoantibodies compared to the synthetic DOR agonist DPDPE. Unlike DPDPE, these autoantibodies display significant immunomodulatory activity as evinced by changes in CCR5 and CXCR4 chemokine receptor expression. The presence of functional autoantibodies in IVIG shows that they are a part of the normal healthy immune repertoire in humans. This work also presents data supporting the interconnecting network between the neuroendocrine and immune systems.

Natural Autoantibodies provides an in-depth analysis of all aspects of natural antibodies. The book examines the advantages and pitfalls of every type of technique that is widely used for detecting autoantibodies. It also covers the sequencing of human autoantibody genes, discussing how sequencing is undertaken and the genetic clues available to elucidate the genetic origins of autoimmunity. Animal models of autoimmunity are also covered, and the up-to-date account provided in this book explains how natural autoantibodies have important regulatory functions and also occasionally serve as templates for autoimmunity. Other topics examined in Natural Autoantibodies: Their Physiological Role and Regulatory Significance include idiotypes of natural autoantibodies; the pathogenic role of natural autoantibodies; and methods to measure the effects of genetic and sex hormones, as well as aging, on natural autoantibodies. The book will be an excellent research tool and reference for immunologists, rheumatologists, and others interested in the topic.

The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

With the contribution from more than one hundred CNS neurotrauma experts, this book provides a comprehensive and up-to-date account on the latest developments in the area of neurotrauma including biomarker studies, experimental models, diagnostic methods, and neurotherapeutic intervention strategies in brain injury research. It discusses neurotrauma mechanisms, biomarker discovery, and neurocognitive and neurobehavioral deficits. Also included are medical interventions and recent neurotherapeutics used in the area of brain injury that have been translated to the area of rehabilitation research. In addition, a section is devoted to models of milder CNS injury, including sports injuries.

This volume illustrates the functional properties of NAbs. Authors from pioneering groups report in their chapters on the tissue homeostatic, tissue regenerating and regulatory properties of NAbs and NAbs in pooled human IgG. Scientists interested in the regulation and modulation of components of the immune system found a whole variety of NAbs to cytokines with regulatory and protective functions and NAbs that modulate, e.g., dendritic cells, regulatory T cells, B cells and granulocytes. Considering the large plasma pools and initial difficulties in preparing IVIG that does not induce adverse effects upon infusion into recipients, this volume ends with a historical chapter on how pooled human plasma was fractionated and the IgG component pretreated for a safe intravenous application.

THE authoritative guide for clinical laboratory immunology For over 40 years the Manual of Molecular and Clinical Laboratory Immunology has served as the premier guide for the clinical immunology laboratory. From basic serology testing to the present wide range of molecular analyses, the Manual has reflected the exponential growth in the field of immunology over the past decades. This eighth edition reflects the latest advances and developments in the diagnosis and treatment of patients with infectious and immune-mediated disorders. The Manual features detailed descriptions of general and specific methodologies, placing special focus on the interpretation of laboratory findings, and covers the immunology of infectious diseases, including specific pathogens, as well as the full range of autoimmune and immunodeficiency diseases, cancer, and transplantation. Written to guide the laboratory director, the Manual will also appeal to other laboratory scientists, especially those working in clinical immunology laboratories, and pathologists. It is also a useful reference for physicians, mid-level providers, medical students, and allied health students with an interest in the role that immunology plays in the clinical laboratory.

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