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After many years of slow progress in the genetic analysis of complex diseases, including multiple sclerosis (MS), the past few years have eventually seen the first steps of turning a frustrating quest into a success story with the identification of a rapidly increasing number of confirmed disease promoting or protecting genetic variants. The principal reason for the change in situation is numbers:...
MS is an immune mediated disease of the central nervous system (CNS) characterized by demyelination, axonal damage and neurologic disability. The primary cause of this CNS disease remains elusive. Here we will address our current understanding of the role of viruses as potential environmental triggers for MS. Virus infections can act peripherally (outside the CNS) or within the CNS. The association...
Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS) that has shaped our understanding of autoimmune tissue inflammation in the central nervous system (CNS). Major therapeutic approaches to MS have been first validated in EAE. Nevertheless, EAE in all its modifications is not able to recapitulate the full range of clinical and histopathogenic aspects of MS...
Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system pathologically characterized by lesions of infiltrating macrophages and T cells. Multiple lines of evidence implicate that T cells play a central role in both mediating and regulating MS pathophysiology, and efforts to develop rational therapeutic strategies for MS have focused on understanding factors which...
Increasing research activities on humoral immune responses involved in the immunopathogenesis of multiple sclerosis (MS) led to a revival of the importance of B cells and antibodies in MS. B cells seem now to play various immunopathogenetic roles in the initiation and propagation of inflammatory demyelinating processes at different disease stages of MS. The biological activities of antibodies in MS...
B cells and T cells are two major players in the pathogenesis of multiple sclerosis (MS) and cooperate at various check points. B cells, besides serving as a source for antibody-secreting plasma cells, are efficient antigen presenting cells for processing of intact myelin antigen and subsequent activation and pro-inflammatory differentiation of T cells. This notion is supported by the immediate clinical...
Natural killer (NK) cells and invariant natural killer T (iNKT) cells are two distinctive lymphocyte populations, each possessing its own unique features. Although NK cells are innate lymphocytes with cytotoxic property, they play an immunoregulatory role in the pathogenesis of autoimmune diseases. NKT cells are T cells expressing invariant TCR a-chains, which are known to bridge innate and adaptive...
CD4+ T cells play a central role in the pathogenesis of multiple sclerosis (MS). Generation, activation and effector function of these cells crucially depends on their interaction with MHC II-peptide complexes displayed by antigen presenting cells (APC). Processing and presentation of self antigens by different APC therefore influences the disease course at all stages. Selection by thymic APC leads...
Multiple sclerosis (MS) is a demyelinating autoimmune disease. However, the persisting neurological deficits in MS patients result from acute axonal injury and chronic neurodegeneration, which are both triggered by the autoreactive immune response. Innate immunity, mainly mediated by activated microglial cells and invading macrophages, appears to contribute to chronic neurodegeneration. Activated...
Immune cells infiltrate the central nervous system (CNS) in many neurological diseases, with a primary or secondary inflammatory component. In the CNS, immune cells employ shared mediators to promote crosstalk with neuronal cells. The net effect of this neuro-immune crosstalk critically depends on the context of the interaction. It has long been established that inflammatory reactions in the CNS can...
A primary focus in autoimmunity is the breakdown of central and peripheral tolerance resulting in the survival and eventual activation of autoreactive T cells. As CD4+ T cells are key contributors to the underlying pathogenic mechanisms responsible for onset and progression of most autoimmune diseases, they are a logical target for therapeutic strategies. One method for restoring self-tolerance is...
In the last few years there has been extraordinary progress in the field of stem cell research. Two types of stem cells populate the bone marrow: haematopoietic stem/progenitor cells (HSC) and mesenchymal stem cells (MSC). The capacity of HSC to repopulate the blood has been known and exploited therapeutically for at least four decades. Today, haematopoietic stem cell transplantation (HSCT) holds...
The current treatments for multiple sclerosis (MS) are, by many measures, not satisfactory. The original interferon-β therapies were not necessarily based on an extensive knowledge of the pathophysiological mechanisms of the disease. As more and more insight has been acquired about the autoimmune mechanisms of MS and, in particular, the molecular targets involved, several treatment approaches have...
Current multiple sclerosis (MS) is generally thought to consist of two general pathological processes; acute inflammation and degeneration. The relationship between these two components is not understood. What is clear, however, is that the measures of acute inflammation are a poor predictor of long-term disability. Although some have suggested that inflammation may not contribute directly to the...
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