Adaptive Immune System
The adaptive immune system is a marvel that only vertebrates are blessed with. This complex mechanism protects us from a wide variety of threats, including viruses and cancer. T cells and B cells, which constitute the backbone of our adaptive immune system, begin their journey in the bone marrow.
B cells mature there, while T cell progenitors migrate to the thymus to eventually become full-grown T cells. There are several types of T cells, which directly kill infected cells, activate other immune cells, and produce cytokines that regulate the immune response. The T and B in the cells’ names designate thymus and bone marrow, respectively.
The thymus is a primary lymphoid organ of the immune system. It is located just behind the sternum, in front of the heart and contains two lobes, an inner medulla and outer cortex, and it acts as an educational system for T cells. Upon their arrival from the bone marrow, thymocytes, future T cells, undergo several stages of development, including two consecutive selection processes. The first one, called positive selection, ensures that the young cells can bind to antigen-presenting receptors on other cells.
The negative selection ensures that the thymocytes do not bind to self-antigens; otherwise, they can end up attacking healthy cells, and when this process fails, it can cause autoimmune disorders. The discipline is harsh: if a cell fails an exam, it is sentenced to death by apoptosis. Upon graduation, T cells migrate to the periphery of the body, where they wait to be activated.
For reasons unknown, the thymus starts degrading early in life, and this involution is particularly rapid during puberty. It shrinks in size and gradually loses its structural integrity, which is crucial for T-cell maturation. Thymic involution is thought to be one of the reasons behind the immune system’s age-related decline and the decreased effectiveness of vaccines in older individuals. Strategies have been proposed for delaying or reversing this process, and one human study has demonstrated a partial reversal of biological age according to an epigenetic clock.
Despite the thymus’s reduced activity with age, thymic cancer generally only affects people over the age of 40. Some forms of lymphoma (a cancer derived from T cells) are more common in early adulthood, but, for the most part, this risk also increases with age.
Several rare congenital defects effect the thymus and can result in severe immunodeficiency throughout an individual’s lifespan. There are multiple autoimmune diseases with origins in the thymus, where the immune system will attack a person’s own cells and can occur at any age.
This age-related decline becomes especially consequential after chemotherapy and radiotherapy that inflict severe damage to the immune system. The thymus, in particular, relies on the intricate crosstalk between its own epithelial cells and thymocytes. When this crosstalk dies out following the therapy-induced depletion of bone marrow cells, thymic involution shifts into high gear.