20 3.2 Role of the Immune System in Multiple Sclerosis

Our immune system serves as a powerful defense mechanism that protects us from a multitude of pathogens. To maximize recognition of all peptides, our immune systems generates T-cell clones with random specificities to both foreign and self-antigens. Fortunately, individuals are often tolerant to self-peptides due to the processing of clones during Thymic Selection. Thymic Selection is a process whereby first, the Thymus positively selects for T-cell clones that have properly rearranged their T-cell receptor (TCR). It then negatively selects for autoreactive T-cells that have a very strong response to self-antigen. However, during this process not all autoreactive T-cells are destroyed, as they can be found in the plasma of healthy individuals (Khailaie et al., 2013). Luckily, our immune system has regulatory T-cells (Tregs), which are the primary cells involved in tolerance mechanisms and keep autoreactive T-cells in check. Tregs do this by secreting a variety of cytokines such as TGFβ, IL-13, and IL-10 that suppress both CD8+ T-cells  and CD4+ T-cells (Saresella et al., 2013).

Figure 2. An overview of the general tolerance mechanism employed by T-regulatory cells. The left hand side of the image represents Thymic Selection where T-cell clones are either selected or destroyed. Upon exposure to antigens, Antigen Presenting Cells (APC) display these antigens and can activate both Regulatory T-cells (Tregs) and CD8+/CD4+ T-cells. Tregs are able to suppress activated T-cells through the release of various cytokines. In MS patients, it has been found that there is a lower frequency of Tregs compared to healthy controls (Kouchaki et al., 2013).

T-cells in the Central Nervous System

While is it unknown how these defective immune cells get into the central nervous system, it is thought that inflammation could weaken the blood-brain barrier and allow for immune cells to enter. Once inside the central nervous system (CNS), autoreactive CD4+ T-cells begin attacking the myelin sheath and affecting the transmission of nerve impulses. Watch this video to get a better understanding of how autoreactive CD4+ T-cells cause demyelination.

This video exemplifies the various immune cells involved in the progression of MS and some treatment options available to patients. Unfortunately, these medications are limited in that they are unable to prevent disease progression and its debilitating consequences. So is that all there is? A complex disease with no cure? Or is there a model out there that we can use to understand MS better? For answers to these questions we can turn to EAE mice, an animal model used in MS research which has provided researchers with a better understanding of MS and novel treatment options.

Before moving onto the next section try this memory game and see how much you learned about each of the different immune cells.

 

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Selected Topics in Health and Disease (2019 Edition) Copyright © by Dr. Ju. All Rights Reserved.

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