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.

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 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.

Natural antibodies (NAbs) are found in normal individuals in the absence of exogenous antigenic stimulation. Natural antibodies rapidly recognize and protect against pathogens that have not been previously encountered. NAbs also cross-react with several self-antigens, which, besides their role as a first line of defense against pathogens, affords them the ability to perform important housekeeping functions in healthy organisms. Such housekeeping functions include the clearance of oxidized damaged structures and/or apoptotic cells, which prevents the induction of pro-inflammatory effects. In addition, NAbs play a role in preventing the expansion of specific auto-reactive clones, thereby behaving as regulatory elements in acute or chronic inflammation. To maintain the non-pathogenic balance between the dual pathogen/self-antigen cross-reactivities of NAbs, a strict regulation in NAb secretion and function is necessary to avoid autoimmune disease. Actually, some of the NAbs related auto-reactivities, such as anti-DNA and anti-MOG, have been associated with autoimmunity. Furthermore, NAbs have been shown to bind to ‘neo-self’ carbohydrate antigens on glycolipids and glycoproteins found on malignant but not normal cells, which suggests NAbs may take part in tumor immunosurveillance. Many aspects regarding NAbs have yet to be studied in more detail: the reactivity and function of NAbs in health and disease, the behavior of the NAb repertoire with increasing age, the regulation of natural antibody production and auto-reactivity, the ways to specifically activate NAbs producing cells with desired specificities, the characteristics of human NAbs, among others. This special topics eBook consists of a number of articles exploring the cells that produce NAbs as well as the characteristics, function, specificity, and/or the role of natural antibodies in health and disease.

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.

Prevalence of autoimmune diseases is increasing. Antibodies are responsible for the humoral type of adaptive immune responses, glycoprotein structure and produced by B lymphocytes. Failure of Immunologic self-tolerance due to environmental and genetic factors may predipose the development of autoimmunity. Self-antigens are either tolerogenic or ignored. Central tolerance occurs at immature T and B lymphocytes in the thymus and bone marrow. Peripheral tolerance occurs at mature lymphocytes encounter self-antigens in peripheral tissues. Negative selection, regulatory T cells, anergy, activation-induced cell death, immune suppression, receptor editing are examples of important steps of immune tolerance. B lymphocytes that produce antibodies which bind self-antigen with medium/low affinity escape from anergy and those antibodies are called as natural autoantibodies but the other ones with high affinity are undergo anergy, The natural antibodies have play critical roles as; discrimination foreign from self, auto-multireactivity, regulate the immunomodulation, maintain tissue homeostasis. Natural autoantibodies work as the templates for the production of pathogenic autoantibodies which has high affinity, switch the class and diverse somatically under proper conditions. Pathogenic autoantibodies can protect or cause diseases via neutralization of self-antigens, opsonization, antibody-dependent cellular cytotoxicity, activation of the complement system, pro-inflammatory and anti-inflammatory effect.

Autoantibodies that are directed against self antigens are called autoantibodies. Not all autoantibodies are harmful. Autoantibodies can be useful in the removal of cell debris during inflammation. Some autoantibodies may be the actual pathogenic agents of autoimmune disease, the secondary consequences of tissue damage, or the harmless footprints of an etiologic agent. In this book, the authors present current research in the detection, pathogenicity and health implications of autoantibodies. Topics include the implicated autoantibodies in kidney disease and Alzheimer's disease; autoimmunity in cardiovascular disease; detection and analysis of natural autoantibodies; and B Cells and autoantibodies in multiple sclerosis.