Immunology of multiple sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelinreactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by meningeal lymphoid follicles with germinal centers.

Correlation of Blood T Cell and Antibody Reactivity to Myelin Proteins with HLA Type and Lesion Localization in Multiple Sclerosis

“…3 is a chronic inflammatory demyelinating disease of the CNS and is a common cause of progressive disability (1,2). Although MS is considered to be an autoimmune disease (1,2), the generally small percentages of individuals showing increased immunoreactivity in their blood to any one autoantigen have raised doubts that autoreactive cells in the blood are of pathogenic relevance.…”

“…Although MS is considered to be an autoimmune disease (1,2), the generally small percentages of individuals showing increased immunoreactivity in their blood to any one autoantigen have raised doubts that autoreactive cells in the blood are of pathogenic relevance. However, if Ag-specific therapy for MS is to be effective, the specific Ags being targeted in individual patients must be known.…”

Sex differences in the clinical presentation and therapy of multiple sclerosis

“…Pored toga, MS je najčešća neurološka bolest i najčešći uzrok onesposobljenosti mladih odraslih osoba (10). Karakteriše je postojanje jasno ograničenih polja demijelinizacije (plakovi) u kojima je, u aktivnoj fazi bolesti, prisutan inflamatorni infiltrat koji se sastoji od CD4+ i CD8+ T-limfocita, B-limfocita, makrofaga i aktivisanih ćelija mikroglije (11). Lezije su diseminovane u beloj masi mozga i kičmene moždine, što dovodi do pojave različitih neuroloških ispada.…”

“…Klinički tok MS i njeni simptomi su takođe heterogeni, odražavajući razlike u vremenskoj i prostornoj diseminaciji lezija u CNS-u. Najčešću formu MS (85% obolelih) karakteriše inicijalna epizoda neurološkog deficita praćena periodom poboljšanja (remisija), posle čega slede naizmenične smene pogoršanja (relapsa) i remisija (relapsno-remitentni oblik MS, RRMS) (11). Vremenom, neurološka oštećenja se akumuliraju i oko 80% obolelih razvija sekundarno progresivni oblik MS (SPMS) (11).…”

“…Najčešću formu MS (85% obolelih) karakteriše inicijalna epizoda neurološkog deficita praćena periodom poboljšanja (remisija), posle čega slede naizmenične smene pogoršanja (relapsa) i remisija (relapsno-remitentni oblik MS, RRMS) (11). Vremenom, neurološka oštećenja se akumuliraju i oko 80% obolelih razvija sekundarno progresivni oblik MS (SPMS) (11). Umesto karakterističnih inflamatornih lezija, javlja se neurodegeneracija, atrofija tkiva i gubitak aksona, što se klinički manifestuje ireverzibilnim neurološkim deficitom.…”