Question

Briefly describe the development of central tolerance to myelin.

Short answer

Briefly describe the development of central tolerance to myelin. Central tolerance to myelin is established through a series of steps: 1) understanding the role of myelin and central tolerance, 2) T cell development and central tolerance processes in the thymus, 3) the role of medullary thymic epithelial cells (mTECs) in presenting self-antigens, 4) the presentation of myelin-derived self-antigens (such as MBP and PLP) by mTECs to eliminate self-reactive T cells during negative selection, and 5) the consequences of impaired central tolerance, such as autoimmune diseases like multiple sclerosis (MS). This process is essential in preventing the immune system from targeting the individual's own neural tissues, avoiding autoimmunity.

Step-by-step solution

Understanding Myelin and Central Tolerance

Myelin is the fatty substance produced by glial cells (oligodendrocytes and Schwann cells) that wraps around the axons of neurons, which helps in the conduction of electrical impulses in the nervous system. Central tolerance is the process by which developing immune cells, specifically T cells and B cells, are rendered unresponsive to self-antigens such as myelin in order to prevent an immune response against an individual's own tissues.

T cell Development and Central Tolerance

T cells develop in the thymus, where they undergo positive and negative selection processes. In positive selection, T cells that recognize self-MHC (major histocompatibility complex) molecules in association with a self-peptide are selected to survive. In negative selection, T cells that bind too strongly to self-antigens presented by MHC molecules are eliminated through apoptosis to avoid autoimmunity.

Role of Medullary Thymic Epithelial Cells (mTECs)

The development of central tolerance to myelin is critically dependent on medullary thymic epithelial cells (mTECs), which express various tissue-specific antigens (TSAs) including self-antigens found in peripheral tissues. mTECs use the Autoimmune Regulator (AIRE) protein to present these self-antigens to maturing T cells to facilitate negative selection.

Myelin as a Self-Antigen during Central Tolerance

Myelin-derived self-antigens, such as myelin basic protein (MBP) and proteolipid protein (PLP), are expressed by mTECs under the regulation of the AIRE protein. T cells that recognize these myelin antigens with high avidity are eliminated during negative selection within the thymus, leading to the development of central tolerance to myelin and preventing these T cells from targeting the individual's own neural tissues.

Consequences of Impaired Central Tolerance to Myelin

If central tolerance to myelin fails to develop properly, autoimmune diseases such as multiple sclerosis (MS) can occur. In MS, the immune system mistakenly targets and destroys the myelin sheath around the axon of nerve cells, leading to impaired nerve function and various neurological symptoms. Proper development of central tolerance to myelin is crucial in preventing such autoimmune responses.