Immunologic Mechanisms of Multiple Sclerosis

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Multiple sclerosis is widely recognized as the most commonly identified cause of progressive neurologic disability in young adults throughout the developed world. The disorder is clinically suspected when patients experience either acute attacks of neurologic compromise or instead are afflicted by a steadily progressive deterioration in functional capabilities. The pathophysiology of acute exacerbations is thought to be related to the development of inflammation and its consequences, within strategic and often discrete central nervous system tract systems. Although a myriad of hypotheses have been formulated to explain the underpinnings of the mechanisms that contribute to both the predilection and triggering of the multiphasic inflammatory events that personify multiple sclerosis, much remains to be done to understand fully the specific set and sequence of events that produce the disease and its cardinal features.

Section snippets

What is the evidence for inflammatory mechanisms underlying tissue injury in multiple sclerosis?

Although those who have worked in this field recognize and appreciate the contributions made by modeling inflammation and cellular trafficking mechanisms in animal models of MS, it is abundantly evident that these models do not fully parody the full complexity of molecular processes that are being elucidated in human inflammatory demyelinating disease. As such, this section avoids any discussion whatsoever as it relates to the use of animal experimentation as it may be related to MS

Epitope spreading

Another process that seems to be relevant to the pathophysiology of MS involves the diversification of the antigenic specificity of immune responses over the course of the disease.37 Such changes influence both cellular and humor limbs of the immune response and represent an important adaptive strategy for ensuring the recognition and neutralization of infectious agents.38 If, however, such reactions are targeted against self-antigens, then the steady amplification and diversity of these

Lymphocyte nomenclature and phenotype

General principles and corresponding generalizations that stem from them can often represent the nidus of great misunderstanding, oversimplification, and strongly held erroneous concepts about how highly complex processes can be codified and reduced to a few concrete models of interaction. When it comes to understanding immune regulation in health or illness, nothing is further from reality. The immune system rivals any of the great creations of the universe. It is endowed with the ability to

Managing cellular trafficking in multiple sclerosis

One of the most important research advances in modern biology has been the elucidation of cellular adhesion pathways. Cellular trafficking (eg, immune system surveillance) across the various tissue compartments of the body is contingent on the use of specific molecular motifs that serve the purpose of physically stabilizing cells to prepare them for transmigration into organ parenchyma. With respect to MS, it is now recognized that an expanded number of cells enter the brain and spinal cord, at

Central nervous system neuroprotection and regeneration

An expanded appreciation now exists for a number of novel injury and potential repair processes within the CNS. A number of neurodevelopmental sequences are activated during the embryologic period that may shed light on potential mechanisms with implications for neuroprotection and potentially even neurorestoration. At the end of development, a receptor signaling system serves to arrest further growth and sprouting of neuritis to ensure their proper distribution and anatomic position. One

Genetic and environmental factors

For quite some time it has been realized that MS is a disorder with both genetic and environmental rudiments.1 Despite this, clinicians continue to search vigorously for new clues on how such factors interact with each other either to protect against MS, or heighten the predilection for developing this autoimmune disorder. It has been learned that the disease is more common in women and whites; is more ominously progressive in African Americans; is more common in family members than in the

The future: where is it?

Enormous progress has been achieved in the capability to diagnose and treat both the disease process itself and its resultant symptoms. Despite these important capabilities, clinicians continue to impact only modestly the most important element of the disease process: progression. A deeper interrogation of the mechanisms that ignite the earliest and perpetuate the latest and constitutive processes in MS will likely reveal cascades of injury that are fundamental to injury and whose modification

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