The immune system has an inherent contradiction in the way it functions – the major role of the immune system is to fight off the invasion of our bodies by bacteria, fungi, viruses and parasites; but in order to accomplish this, immune cells need to recognize our own tissues so that they can determine what is foreign when we have an infection.
2018 May 30. doi: 10.1089/rej.2017.2049
Proteostasis, which includes the repair and disposal of misfolded proteins, depends, in part, on the activity of heat shock proteins (HSPs), a well-known class of chaperone molecules. When this process fails, abnormally folded proteins may accumulate in cells, tissues, and blood. These species are a hallmark of protein aggregation diseases, but also amass during aging, often in the absence of an identified clinical disorder.
We have worked on the JC virus for many months to understand how this virus travels to the brain causing PML (Progressive Multifocal Leukoencephalopathy) a serious and potentially fatal infection which complicates a number of MS therapies including Tysabri, Tecfidera, Gilenya, Ocrevus and Lemtrada. This infection also complicates treatments for other autoimmune diseases, transplantation and chemotherapy; and is seen in different immune deficiencies and HIV-AIDS. There are at least 15 monoclonal antibody treatments for different conditions which are complicated by the JC virus.
Most data supports that the major culprit in the formation of Multiple Sclerosis is the T-cell, which is a white blood cell that plays a key role in the immune system. These cells are named after the small organ – the thymus gland – where they are produced. In particular, MS is an immune-mediated autoimmune disease caused, in all probability, by a defect in regulatory T-cells: cells which regulate, or maintain order in the immune system, and suppress immune responses either by cell-cell contact or by secreting cytokines (proteins) to regulate the extent of potentially damaging inflammation to the tissues of the body. Unrestrained activation of effector T cells (normally controlled by regulatory T cells) allows them to produce pro-inflammatory cytokines and recruit other inflammatory immune cells to a tissue causing damage such as myelin injury as seen in MS. The consequence of inflammation in MS, in all probability, is a chronic neurodegenerative process called Progressive MS, which is an additional level of complexity that is being intensively investigated.