DC activation/maturation - or life cycle
As we have already heard, DCs are “hungry”, star-shaped cells found in almost all of the tissues of the body. We also know that they are constantly sampling their environment. Under normal circumstances, immature DCs take up self-antigens from cells which naturally die by apoptosis. These self-antigens are then presented to memory T cells in the tissue but will not evoke an immune response, and why should it!? There is nothing present to attack! So what is different during an infection? Well, during an infection surface PRRs on DCs recognize PAMPs like a lock and key causing DCs to become activated. As the DC becomes activated it changes and these changes make a huge difference for how the T cell now sees the antigen and results in an immune response. It is not just PAMPs that can activate DCs. NK cells are able to activate DCs, as can histamine released from mast cells, danger signals like ATP and pro-inflammatory cytokines like TNF-α. Activation initiates a maturation process in the DC. So let’s take a look at what these maturation associated changes are in more detail.
During the process of maturation, DCs change their surface molecule repertoire. They become less able to capture antigen because they remove receptors involved in antigen capturing such as Fcγ and Fcε receptors, and more skilled at antigen presenting and T cell activation. One reason why they become more skilled at antigen presentation is because they increase the copy number of MHC class II molecules, co-stimulatory molecules CD80, CD86, CD40 and adhesion molecules CD54 and CD58 on their surface. However, the maturation process also results in production of cytokines such as IL-12, TNF-α and IL-6 and changes in expression of chemokine receptors. With new chemokine receptors, DCs can now respond to other chemokines, which causes DCs to lose their grip on the site of infection and get lured into the lymph - en route to lymph nodes where naive T cells reside. When you watch this video, try imagining all these activation induced changes taking place and how these changes improves the DCs' ability to activate T cell.
Did you notice that the DC was able to keep the MHC class II/peptides on the cell surface for the duration of the trip to the lymph nodes? Can you remember what we called that process? The mature DC has a short life span and dies shortly after activation.