Autoimmune diseases and their relation with immunological, neurological and endocrinological axes (original) (raw)

Autoimmunity: the moving boundaries between physiology and pathology

Journal of Autoimmunity, 1988

This paper considers current concepts of autoimmunity and concludes with a discussion on the need for viable alternatives. It is argued that, if a century of 'horror autotoxicus' and over 30 years of active research based on 'clonal deletion' models have failed to contribute solutions to the problem, these notions are probably inadequate. Instead, it is proposed that pathological states of autoimmunity should be considered as deviations from normal autoreactivity which is a central property of the immune system. It follows that the study of autoimmunephysiology is necessary to the understanding ofpathology.

Mechanisms and Pathophysiology of Autoimmune Disease

Clinical Reviews in Allergy & Immunology, 2012

The first textbook on autoimmunity was published by Ian Mackay and McFarland Burnett in 1963. It was the first attempt to summarize existing knowledge on human autoimmunity. Since that time, there have been tens of thousands of experimental papers and numerous textbooks that focus on the diagnosis and treatment of human autoimmunity. There have been at least as many, if not more, directed at similar issues in animal models. Enormous strides have been made not only in diagnosis, but also in the pathophysiology and especially in treatment. We have gone from the era of simple HLA typing to deep sequencing and, more recently, epigenetic analysis. We have gone from the era of white blood cell differentials to detailed lymphoid phenotyping. We have gone from the era of simple antinuclear antibodies to detailed and sophisticated immunodiagnosis with recombinant autoantigens and disease-specific epitopes. We have gone from the era of using only corticosteroids to selective biologic agents. Diseases that were previously considered idiopathic are now very much understood as autoimmune. We are in the era of autoinflammatory reactions and the concept of both innate versus adaptive immunity in mediating immunopathology. In this edition of Clinical Reviews in Allergy and Immunology, we focus on key and cutting-edge issues in the pathophysiology of autoimmunity. The issues are very much oriented and driven by hypothesis, i.e., a prediction of events expected to occur based on observations. It is not meant to be a complete summary of potential mechanisms of autoimmunity, but rather an attempt to accelerate discussion and better understanding. The primary goal is obviously to help our patients with autoimmune disease.

Immune-Neuroendocrine Interactions and Autoimmune Diseases

Clinical and Developmental Immunology, 2006

The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggest...

Pathophysiological mechanisms of autoimmunity

Annals of the New York Academy of Sciences

Autoimmune diseases (AIDs) are chronic disorders characterized by inflammatory reactions against self-antigens that can either be systemic or organ-specific. AIDs can differ in their epidemiologic features and clinical presentations, yet all share a remarkable complexity. AIDs result from an interplay of genetic and epigenetic factors with environmental components that are associated with imbalances in the immune system. Many of the pathogenic mechanisms of AIDs are also implicated in Myasthenia Gravis (MG), an autoimmune disease where inflammation of the thymus leads to a neuromuscular disorder. The goal of this review is to highlight the similarities and differences between MG and other AIDs by reviewing the common transcriptome signatures and the development of germinal centers, and by discussing some unsolved questions about autoimmune mechanisms. This review will propose hypotheses to explain the origin of regulatory T (Treg) cell defects and the causes of chronicity and specificity of AIDs.

The mosaic of autoimmunity: hormonal and environmental factors involved in autoimmune diseases–2008

Isr Med Assoc J, 2008

Yehuda Shoenfeld MD 1*, Gisele Zandman-Goddard MD 2, Ljudmila Stojanovich MD 3, Maurizio Cutolo MD 4, Howard Amital MD 5, Yair Levy MD 6, Mahmoud Abu-Shakra MD 7, Ori Barzilai MD 1, Yackov Berkun MD, Miri Blank PhD 9, Joselio Freire de Carvalho MD 10 ...

Cellular and Molecular Mechanisms of Autoimmune Disease

Toxicologic Pathology, 2011

Autoimmune disease (AIDx) results from failure to sustain tolerance to self molecules. Dozens of AIDx involving one or multiple organ systems afflict 3% or more of people worldwide (>75% women). Predisposing factors for AIDx include genetic background, hormonal status, pathogens, and xenobiotic exposures. The incidence of AIDx is higher in individuals living in developed nations, including recent immigrants. Patients may have several AIDx simultaneously. Certain AIDx can prevent other AIDx. A history of AIDx raises the risk for developing hematopoietic neoplasia. Some common mechanisms for losing self-tolerance include reduced deletion or enhanced activation of autoreactive CD4+ T-helper (Th) lymphocytes, defective immunomodulation by CD4+ regulatory (Treg) and CD8+ suppressor (Ts) T-lymphocytes, dysregulated signaling (leading to a relative increase in pro-inflammatory cytokines), comparable structure between self-antigens and foreign molecules, or expression of new epitopes on ...

Molecular and Cellular Mechanisms Associated with Autoimmune Diseases

International Journal of Environmental Research and Public Health, 2004

Evidence points to increases in the incidence and prevalence of several autoimmune diseases in the United States. As a result, the cost to public health from clinical management of autoimmune conditions is on the rise. The initiation and progression of autoimmune disturbances involves both genetic and environmental factors. Deficiencies in important proteins that normally participate in maintaining checks and balances

Autoimmune Disorders: An Overview of Molecular and Cellular Basis in Today’s Perspective

Journal of Clinical & Cellular Immunology, 2013

Autoimmunity arises when immune responses mounted in the host are directed against self-components. Autoimmune diseases are pathophysiological states that result from a loss of self-tolerance and the consequent immune destruction of host tissues. Autoimmunity is mediated by a variety of molecular and cellular events, and responses. The development of an autoimmune disease is a very complex process in which recognition of selfantigens by lymphocytes is centrally involved in pathologic organ damage. Autoimmune disease is inherited as a complex trait, with multiple loci controlling various aspects of disease susceptibility. More recently, some of these susceptibility genes have been identified. Certain environmental influences, such as cigarette smoke, ultraviolet light, or infectious agents, may interplay with this genetic predisposition to initiate the disease process. Silica exposure and its role in systemic lupus erythematosus (SLE) have been identified in studies of occupational exposure, and experimental studies have explored potential mechanisms related to immune dysregulation. Some autoimmune responses emerge following infection by a pathogen, whose protein(s) hold structural similarities to regions on proteins of the host. Thus, antibodies evoked against a pathogen might cross-react with a self-protein and act as autoantibodies, and the concerned autoantigen then provides a source for persistent stimulation. Evidence is emerging that activation of autoimmune B cells and T cells can be influenced by innate immune receptors, such as Toll-like receptors, which primarily recognize pathogen-derived molecular structures but may cross-react with host molecules. Proteins to which the immune system is generally self-tolerant might, if altered, elicit autoimmune responses. Potential involvement of chaperones in the induction of autoimmune disease pathogenesis has also been explored. The contributions of microRNA to pathogenesis of autoimmune diseases like SLE are beginning to be uncovered and may provide us a new arena for exploration of mechanisms responsible for initiation and pathogenesis of autoimmune diseases.