Table 1.

Categories of immune therapies in MS.

I Non-cell-specific interference with DNA synthesis and interference with DNA repair	Mitoxantrone	Topoisomerase-II inhibitor, inhibits DNA synthesis, affects primarily quickly dividing cells
	Cyclophosphamide	Alkylating chemotherapeutic agent, interferes with mitosis and cell replication, causes suppression of cell-mediated and humoral immunity, decreases secretion of Th1 cytokine IFNγ and IL-12, increases secretion of Th2 cytokines IL-4 and IL-10 in CSF and peripheral blood
II Pleiotropic immunomodulation of the immune system	IFNs	Th1/Th2 shift, APC modulation, production of BDNF
	GA	Binds to MHC, influences antigen-presentation, changes Th1:Th2 ratio; induces an in vivo change of the frequency, cytokine secretion pattern and the effector function of GA-specific CD4+ and CD8+ T cells, induces neurotrophic factors, suppresses inflammation via Th2 cells
	Dimethyl fumarate	Modulates cytokine expression, inhibits immune cell proliferation, activates Nrf2, possible lymphocyte apoptosis
III Cell-specific interference with DNA synthesis	Teriflunomide	DHODH inhibition, thereby inhibits the proliferation of activated lymphocytes
	Cladribine	Chlorinated analogue of deoxyadenosine; inhibition of DNA synthesis and impaired repair of DNA strand breaks; selectivity owing to preferential accumulation in lymphocytes.
	Azathioprine	Purine analogue structurally similar to cladribine but less selective. Inhibition of DNA and RNA synthesis owing to purine depletion, especially (but not exclusively) in T cells, B cells and NK cells.
IV Peripheral sequestration of leukocytes	Natalizumab	mAb against α4b-1 integrin, inhibits the binding of immune cells to endothelial cells via VLA4-VCAM
	Fingolimod	Functional S1P antagonist, keeps lymphocytes in the lymphatic organs
V Depletion of immune cells	Alemtuzumab	mAb against CD52, quick elimination of CD52+immune cells from the circulation, ‘organized’ repopulation and by this immune regulation
	Rituximab	Genetically produced mAb against CD20, quickly depletes CD20-expressing B-cell populations
	Ocrelizumab	Humanized recombinant Ab targeting CD20 in B cells, induces a rapid elimination of circulating CD20+ B-cell subpopulations

Ab, antibody; APC, antigen-presenting cells; BDNF, brain-derived neurotrophic factor; CSF, cerebrospinal fluid; DHODH, dihydroorotate dehydrogenase; GA, glatiramer acetate; IFN, interferon; IL, interleukin; mAb, monoclonal antibody; MHC, major histocompatibility complex; NK, natural killer; VLA4, very late antigen 4/ VCAM, vascular cell adhesion molecule 1.