Multiple sclerosis (MS) is considered an autoimmune chronic inflammatory disease of the central nervous system ( CN S) characterized b y demyelination and axonal damage. It is widely accepted that MS immune response compartmentalized within the CNS is mediated by autoreactive major histocompatibility complex (MHC) class II–restricted CD4+ T cells trafficking across the blood–brain barrier (BBB) after activation and secreting T helper 1 (Th1)-type pro-inflammatory cytokines. These cells seem to regulate a combined attack of both innate and acquired immune responses directed against myelin proteins, which includes macrophages, MHC class I–restricted CD8+ T cells, B cells, natural killer (NK) cells, and γδ T cells. This coordinated assault is also directed toward neurons and results in axonal loss. However, although the understanding of the mechanisms that orchestrate the development and the progression of the disease has recently received increasing attention, the sequence of events leading to myelin and axonal injury currently remains uncertain. Failure of peripheral immunologic tolerance is hypothesized to play a crucial role in the initiation of MS, but evidence for a single triggering factor is lacking. In addition, the different theories proposed to explain this crucial step, suggesting the involvement of an infectious agent, a dysfunction of regulatory pathways in the periphery and a primary neurodegeneration, are difficult to reconcile. On the other hand, the view of MS as a “two-stage disease,” with a predominant inflammatory demyelination in the early phase (relapsing–remitting MS form) and a subsequent secondary neurodegeneration in the late phase (secondary or primary progressive MS) of the disease, is now challenged by the demonstration that axonal destruction may occur independently of inflammation and may also produce it. Therefore, as CNS inflammation and degeneration can coexist throughout the course of the disease, MS may be a “simultaneous two-component disease,” in which the combination of neuroinflammation and neurodegeneration promotes irreversible disability.

Neuroimmune interaction that operate in the development and progression of inflammatory demyelinating diseases: lessons from pathogenesis of multiple sclerosis

FAINARDI, Enrico;CASTELLAZZI, Massimiliano
2009

Abstract

Multiple sclerosis (MS) is considered an autoimmune chronic inflammatory disease of the central nervous system ( CN S) characterized b y demyelination and axonal damage. It is widely accepted that MS immune response compartmentalized within the CNS is mediated by autoreactive major histocompatibility complex (MHC) class II–restricted CD4+ T cells trafficking across the blood–brain barrier (BBB) after activation and secreting T helper 1 (Th1)-type pro-inflammatory cytokines. These cells seem to regulate a combined attack of both innate and acquired immune responses directed against myelin proteins, which includes macrophages, MHC class I–restricted CD8+ T cells, B cells, natural killer (NK) cells, and γδ T cells. This coordinated assault is also directed toward neurons and results in axonal loss. However, although the understanding of the mechanisms that orchestrate the development and the progression of the disease has recently received increasing attention, the sequence of events leading to myelin and axonal injury currently remains uncertain. Failure of peripheral immunologic tolerance is hypothesized to play a crucial role in the initiation of MS, but evidence for a single triggering factor is lacking. In addition, the different theories proposed to explain this crucial step, suggesting the involvement of an infectious agent, a dysfunction of regulatory pathways in the periphery and a primary neurodegeneration, are difficult to reconcile. On the other hand, the view of MS as a “two-stage disease,” with a predominant inflammatory demyelination in the early phase (relapsing–remitting MS form) and a subsequent secondary neurodegeneration in the late phase (secondary or primary progressive MS) of the disease, is now challenged by the demonstration that axonal destruction may occur independently of inflammation and may also produce it. Therefore, as CNS inflammation and degeneration can coexist throughout the course of the disease, MS may be a “simultaneous two-component disease,” in which the combination of neuroinflammation and neurodegeneration promotes irreversible disability.
9780195326697
central nervous system; immune surveillance; inflammation; tissue damage; multiple sclerosis
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/532799
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact