Humoral Immunity In Neurological Diseases

Over the last years it has become evident that many neurological diseases of the central nervous system (CNS) are induced by a specific adaptive immune response directed against molecules expressed on CNS-resident cells. Well-recognized examples are anti-N-Methyl-D-Aspartate Receptor (NMDAR) encephalitis which is characterized by the presence of antibodies against neuron-expressed NMDAR, or neuromyelitis optica (NMO), induced by antibodies to astrocyte-expressed aquaporin-4. Many more examples exist, and antibodies, and T or/and B cells have increasingly been associated with CNS disease. Often the symptoms of these diseases have not been typically reported to have an immune aetiology. Beside classical neurological symptoms like ataxia, vision disturbance, and motor or sensory symptoms, these can include cognitive disturbances, behavioral abnormalities, or/and epileptic seizures. Although much has been learned regarding the pathophysiology of prototypic examples of these disorders, there are still major gaps in our understanding of their biology. This may be due to the fact that they are rare diseases, and their therapies are still very limited. This research topic includes contributions addressing the analysis of the adaptive immune response driving disease including target antigens, molecular epitope mapping, and factors involved in the disease pathogenesis such as complement activation cascades, genetic and genomic regulation, as well as environmental triggers. Diagnostic criteria and methods, and treatment are also discussed. The overall aim of the volume is to review progress in our pathophysiological understanding of immune-mediated CNS disorders in order to advance diagnostic and therapeutic approaches, and ultimately improve outcomes for patients.

The book covers the immunological and clinical aspects of immune-mediated diseases of the central and peripheral nervous system, excluding multiple sclerosis. It includes paraneoplastic neurological disorders, and discusses the immune mechanisms in the growing number of recognised paraneoplastic conditions. It not only provides an overview of the field but also discusses the possible role of immunity in other neurological disorders such as epilepsy. Chapters are written by scientists and clinicians directly involved in each specific area, who have summarized the current understanding of neuroimmunology, with emphasis on the underlying abormalities of the immune responses, the different clinical expression of the diseases and the important use of immunotherapies in treatment. Figures and tables are included in each chapter.

Inflammation of the brain in the context of neurodegenerative disorders is an area of intense debate and discussion, not least in terms of its pathogenic significance and the extent to which it drives disease processes and pathology. This inflammation can take several forms including innate responses recruiting microglia, humoral responses involving antibody, complement mediated processes and cellular T-cell activation, of which the role and extent of each may differ between diseases. Whilst some diseases have been more intensely linked to inflammation and long-term degeneration (e.g. MS), more traditional chronic neurodegenerative disorders have been thought of in terms of intrinsic neuronal pathology with a secondary innate response. However, it has been described that microglia activation is an early event of many degenerative disorders and evidence is accumulating that it may play a critical role in actually causing pathology and driving disease processes. If true, this would have major therapeutic implications, but what is the evidence that this is the case? The initial observations by Patrick McGeer’s group of post-mortem tissue from patients with Parkinson’s disease revealed the presence of activated brain microglia and has thus lead to the hypothesis that chronic inflammation could participate to neuronal degenerative processes. The significance of these original observations has only been recently revisited, and the development of more powerful tools to study the brain immune response has certainly contributed to this field of research. Chronic inflammation in the brain can take many forms but of particular interest has been the resident microglia and the role they play in this process. In this context, microglia have often been thought to become activated only after the disease has begun and then to contribute minimally to the degenerative process. Emerging new concepts challenge this view by proposing that microglial senescence, for example, may release the disease process and/or accelerate it. In addition, microglia, once activated, can adopt different phenotypes which can be both pro-inflammatory and pro-repair and may impact not only on the healthy adult neuronal population but on those new neurons derived from neurogenic niches of the adult brain. In this Research Topic, we attempt to explore this by first considering the innate immune responses in the brain and the methods by which they can be studied experimentally and in patients with various neurodegenerative disorders. This sets the scene for then discussing a range of different disorders including Alzheimer’s, Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis. These papers seek to discuss the evidence for an innate immune response and whether this is beneficial or detrimental, as well as its therapeutic implications.

The last decade has seen an upsurge of information on the role of immune responses in neurodegenerative disorders. In many of these diseases it is still unclear whether the innate and adaptive responses are pathogenic or play a role in repair, and thus understanding their precise roles is key to controlling these diseases by designing immune-therapeutic approaches. The connection between many neurological diseases is the realisation that the immune and nervous systems are inextricable linked, and that perturbations in this delicate balance are involved in many disorders. This has opened up new avenues for therapeutic approaches to treatment of CNS inflammatory and neurodegenerative disorders. Neuroinflammation and CNS Disorders brings together the very latest information on the interactions between the immune system and central nervous system. The first section of the book highlights the basic concepts in the field whilst the second section, the main body of the book, covers the role of the immune response in specific disorders of the central nervous system. Neuroinflammation and CNS Disorders will provide an invaluable guide for both researchers and clinicians working in this complex and dynamic field.

The Molecular Immunology of Neurological Diseases provides a comprehensive review of current updates in molecular immunogenetics of different neurological diseases. Readers will learn about the role of immune cells and their modulation strategies to help in the development of therapeutic approaches for both acute and chronic neurodegenerative disorders. There is no other book available on the topic. It has long been thought that the brain is an immune-privilege organ with very limited immune response. However recent studies have made clear that both systemic 'brain' and peripheral 'blood' immune cell responses play key roles in determining brain pathology in neurodegenerative disorders. This book summarizes the role of immune cell activation in the central nervous system microenvironment in acute and chronic neurodegenerative disorders. In addition, it discusses the key role of immune cells and their modulation strategies for the development of current therapeutic approaches. Discusses the molecular immunogenetics of different neurological diseases Covers strategies for the development of therapeutic approaches Encompasses both acute and chronic neurogenerative disorders Describes the molecular pathogenesis of viral genes in various diseases Features chapters on migraine, muscular dystrophy and cancer

In spite of progress in biomedical research, we know little about the causes, prevention, and treatment of the numerous mental and neurological disorders that afflict up to 15% of all individuals. In the last decade, great advances have been made in the physiopathology of mental and neurological disorders, leading to at least a partial control of Parkinson's disease, epilepsy, certain psychoses, and anxiety syndromes. Despite the fact that an underlying specific neurotransmitter deficiency has been demonstrated in Alzheimer's and Parkinson's diseases, the immune dysfunction and viral hypotheses continue to be attractive for investigators dealing with these degenerative diseases of the aging brain, which afflict 10% of senior citizens. A retrospective epidemiologic study suggests that the encephalitis lethargica and parkinsonism were almost certainly caused by the 1918 influenza virus pandemics. It must be stressed that the etiopathogenesis of many mental disorders is not known, and this ignorance has led to several untenable neurophysiological and biochemical hypotheses. Epidemiologic investigations show a high prevalence of functional psychoses and organic mental disorders. Although many of them are conceptualized as biopsychosocial disorders, recent data indicate that the biological component appears more and more as a major etiologic factor. Among the various biological hypotheses, the viral and im munologic concept has become a significant one. In view of recent discoveries in virology and immunity, it becomes clear that viral and immunologic hypotheses should be inves tigated more systematically concerning the mechanisms of numerous mental and neu rological disorders.