T-cell development

Your immune system is like the military - with two main branches, the innate immune response and the adaptive immune response. The innate immune response is immediate and non-specific, meaning that although it can distinguish an invader from a human cell, it doesn’t distinguish one invader from another invader. In contrast, the adaptive immune response is highly specific for each invader, and that’s because the cells of the adaptive immune response have receptors that differentiate one pathogen from another by their unique parts - called antigens. This adaptive immune response takes days to weeks to become activated, during which time the innate immune system provides protection. The second important feature of the adaptive immune response is that it has memory, which means that once a response against an antigen is triggered, subsequent responses will be faster and stronger. This, of course, is why vaccines are so effective – once you get a vaccine containing a part of a pathogen, the next time you see that same pathogen, you will remember the previous encounter (from the vaccine) and you will kill it.

Now, the key cells of the adaptive immune response are the lymphocytes - the B and T cells - which are generated during lymphopoiesis. Lymphopoiesis has two main goals - to generate a diverse set of lymphocytes, each with a unique antigen receptor, and to get rid of lymphocytes that have receptors that are self-reactive, meaning that they could attack one’s own healthy tissue. Normally, hematopoietic stem cells within the bone marrow mature into a common lymphoid progenitor cell, which then becomes either a B-cell or a T cell. To become a B cell, it has to develop into an immature B-cell in the bone marrow and then complete its maturation in the spleen. To become a T cell, it has to migrate to the thymus and become a thymocyte, where it completes its development into a mature T cell. So, “B” for bone marrow and “T” for thymus.

In T cell development, the common lymphoid progenitor leaves the bone marrow and goes to the thymus, because that’s where the developing T cells or thymocytes mature. The thymus is a fatty organ that sits in front of the heart, and as we age, much like our waistlines, the thymus get fattier and fattier. This fat crowds out the space that used to be reserved for T cell development, and it’s one reason why cell mediated immunity declines over time - a process called involution of the thymus. So the thymus has an outer cortex, and an inner medulla. Within the medulla, there are epithelial cells as well as dendritic cells. Both thymic epithelial cells and dendritic cells present antigens to developing T cells on molecules called major histocompatibility complexes or MHC molecules. Thymic epithelial cells will also support the developing T cells. Now, antigen presentation is important because T cells have T cell receptors that can only bind peptide antigens if they’re displayed on an MHC molecule - which is sort of like a silver platter. So if the T cell receptor can’t bind to the MHC molecule, then the T cell isn’t going to able to do its job.