Chapter Two
Literature Review
2.1 Multiple Sclerosis
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that remains incurable. The disease manifests as a wide range of neurological deficits including cognitive impairment, impaired coordination, visual disturbances, and extremity numbness (Weinshenker et al., 1989). MS affects approximately 400,000 people in the US and 2.5 million worldwide and it is the most common inflammatory neurological disease among young and middle age adults. MS is prevalent in females (Harbo et al., 2013) with reports suggesting sex-linked genetics traits and hormonal impact as plausible causes for this predominance (Quintero et al., 2012) . MS-related healthcare costs are …show more content…
The most common classification is the relapsing-remitting MS (RRMS) that accounts for approximately 80-85 percent of all MS cases at the time of diagnosis (Weinshenker et al., 1989). RRMS is characterized by acute periods where symptoms and disability exacerbates followed by remission periods where symptoms and disability resolves to varying degrees. Neurologic dysfunction and disability accumulates over many years and patients often develop secondary progressive MS (SPMS) where relapses are uncommon as disease progresses (Loleit et al., 2014). Another form of MS is the primary progressive MS (PPMS), in which accumulation of disability happens independently of exacerbations. There are many immunomodulatory therapies to treat RRMS with many patients having appositive prognosis, however PPMS patients do not have the same …show more content…
First, slow rolling of on endothelial walls allow activated leukocytes to identify proper arrays of chemoattractants and integrin ligands. Prolonged selectin-mediated rolling of neutrophils and lymphocytes may also lead to integrin activation. Once firmly arrested, integrins serve for leukocytes to bind to other blood-borne leukocytes and platelets. Activated T cells and B cell blasts express high levels of adhesive integrins (Engelhardt, 2006). All other leukocytes maintain their integrins in mostly inactive states and must undergo in situ modulation to develop high avidity for their special ligands. Following rolling, the arrest of lymphocytes and myeloid cells in venules is mediated by the in situ activation of at least one of four main integrins: α4 β7, LFA-1 (αLβ2, CD11a/CD18), Mac-1 (αΜβ2, CD11b/CD18), or VLA-4 (α4β1). Integrins of the β1 subfamily, specifically VLA-1, VLA-2, VLA-4, VLA-5 and VLA-6, have been shown to facilitate leukocyte migration across extracellular matrix. It is important to note that there is considerable redundancy: multiple ligands have been identified for a single receptor, and multiple receptros bind a single ligand (Lowell et al., 2012). The proadhesive properties of integrins are overlapping and additive, and depend on specific cytoskeletal and transmembrane associations with cytoskeletal adaptor molecules. Integrins are activated bidirectionally:
Literature Review
2.1 Multiple Sclerosis
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that remains incurable. The disease manifests as a wide range of neurological deficits including cognitive impairment, impaired coordination, visual disturbances, and extremity numbness (Weinshenker et al., 1989). MS affects approximately 400,000 people in the US and 2.5 million worldwide and it is the most common inflammatory neurological disease among young and middle age adults. MS is prevalent in females (Harbo et al., 2013) with reports suggesting sex-linked genetics traits and hormonal impact as plausible causes for this predominance (Quintero et al., 2012) . MS-related healthcare costs are …show more content…
The most common classification is the relapsing-remitting MS (RRMS) that accounts for approximately 80-85 percent of all MS cases at the time of diagnosis (Weinshenker et al., 1989). RRMS is characterized by acute periods where symptoms and disability exacerbates followed by remission periods where symptoms and disability resolves to varying degrees. Neurologic dysfunction and disability accumulates over many years and patients often develop secondary progressive MS (SPMS) where relapses are uncommon as disease progresses (Loleit et al., 2014). Another form of MS is the primary progressive MS (PPMS), in which accumulation of disability happens independently of exacerbations. There are many immunomodulatory therapies to treat RRMS with many patients having appositive prognosis, however PPMS patients do not have the same …show more content…
First, slow rolling of on endothelial walls allow activated leukocytes to identify proper arrays of chemoattractants and integrin ligands. Prolonged selectin-mediated rolling of neutrophils and lymphocytes may also lead to integrin activation. Once firmly arrested, integrins serve for leukocytes to bind to other blood-borne leukocytes and platelets. Activated T cells and B cell blasts express high levels of adhesive integrins (Engelhardt, 2006). All other leukocytes maintain their integrins in mostly inactive states and must undergo in situ modulation to develop high avidity for their special ligands. Following rolling, the arrest of lymphocytes and myeloid cells in venules is mediated by the in situ activation of at least one of four main integrins: α4 β7, LFA-1 (αLβ2, CD11a/CD18), Mac-1 (αΜβ2, CD11b/CD18), or VLA-4 (α4β1). Integrins of the β1 subfamily, specifically VLA-1, VLA-2, VLA-4, VLA-5 and VLA-6, have been shown to facilitate leukocyte migration across extracellular matrix. It is important to note that there is considerable redundancy: multiple ligands have been identified for a single receptor, and multiple receptros bind a single ligand (Lowell et al., 2012). The proadhesive properties of integrins are overlapping and additive, and depend on specific cytoskeletal and transmembrane associations with cytoskeletal adaptor molecules. Integrins are activated bidirectionally: