Immune System's Harmony: A Comparative Analysis of Multiple Sclerosis and Healthy States

In healthy individuals, the immune system maintains a balance between different T cell subsets, such as Th1, Th2, Th17, and regulatory T cells (Tregs), to protect the body from infections while preventing autoimmune responses. However, in multiple sclerosis (MS) patients, this balance is disrupted, leading to an increased activation of autoreactive T cells, particularly Th1 and Th17 cells, which are associated with inflammation and damage to the myelin sheath​​​​.

Th1 cells produce pro-inflammatory cytokines like interferon-gamma (IFN-γ), which activate macrophages and promote inflammation. Th17 cells secrete interleukin-17 (IL-17), which recruits neutrophils and amplifies the inflammatory response. In contrast, Tregs usually help maintain immune tolerance and suppress excessive immune responses. In MS, the function of Tregs is often impaired, further contributing to the loss of immune balance​​​​.

The disruption of immune cell balance in MS is also influenced by genetic factors. For example, variations within the major histocompatibility complex (MHC), particularly the HLA-DRB1 alleles, exert a significant effect on MS risk. Genome-wide association studies (GWAS) have identified more than 20 additional risk loci that are associated with MS, many of which are related to immune function and implicate T-helper-cell differentiation in the pathogenesis of the disease​​.

B cells also play a role in MS. They can act as antigen-presenting cells, produce autoantibodies, and secrete pro-inflammatory cytokines. The interaction between B cells and T cells, known as immune-cell crosstalk, is implicated in the pathogenesis of MS​​.

In summary, the immune system in MS patients is characterized by an imbalance in T cell subsets, with increased activation of autoreactive Th1 and Th17 cells and impaired regulatory T cell function. This imbalance is influenced by genetic factors that affect immune cell differentiation and function. Understanding these differences between healthy individuals and MS patients is crucial for developing targeted therapies to modulate the immune response in MS​​​​​​​​.

Reference:

Attfield, K. E., Jensen, L. T., Kaufmann, M., Friese, M. A., & Fugger, L. (2022). The immunology of multiple sclerosis. Nature Reviews Immunology, 22(12), 734-750.
Kasper, L. H., & Shoemaker, J. (2010). Multiple sclerosis immunology: the healthy immune system vs the MS immune system. Neurology, 74(1 Supplement 1), S2-S8.
Sawcer, S., Hellenthal, G., Pirinen, M., Spencer, C. C., Patsopoulos, N. A., Moutsianas, L., ... & Giannoulatou, E. (2011). International Multiple Sclerosis Genetics Consortium Wellcome Trust Case Control Consortium 2 Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature, 476(7359), 214-219.
Ransohoff, R. M. (2018). Immune-cell crosstalk in multiple sclerosis.