I have recently begun a project as part of my master’s year for university, focussing on a key molecule in cells that coordinate the immune response. Having been given insight into the complex and fascinating workings of the immune system, I thought I would share some info on a major aspect of it, T-cells!! Please bear with me through all the confusing names and everything – scientists love long complicated words!
Let’s start with basics; the immune system is composed of the innate and the adaptive immune system. The former is the non-specific defence against infection through physical and chemical barriers such as the skin which blocks the entry of foreign bacteria and viruses. It also includes phagocytes, a type of cell which engulfs pathogens and destroys them using hydrolytic enzymes. In contrast to this form of defence, the adaptive immune system is highly specialised and able to induce a variety of cascade signals to fight infection.
A key feature of the adaptive immune response is the use of lymphocytes – a types of white blood cells that can recognise pathogens, coordinate an appropriate response and produce memory cells that undergo rapid proliferation upon the detection of a second infection. T-cells are a subset class of lymphocytes which are denoted by the presence of the T-cell receptor (TCR) on its plasma membrane. They can be categorised into different groups depending on their function, such as killer T-cells or helper T-cells which both do pretty much what it says, but can also be classified into two categories depending on their expression of the TCR co-receptor glycoproteins, CD4 positive (CD4+) or CD8 positive (CD8+). Their classification is determined through how the T-cell interacts with something called the major histocompatibility complex (MHC). The MHC is a receptor complex on the surface of cells which, under invasion of foreign pathogens, presents non-self-antigens (made up of foreign protein fragments) to the cells of the immune system, to signal that the cell is infected – shown in the figure below. These are also divided into two subsets (just to make matters even more confusing) labelled Class I and Class II MHCs. Class I complexes are present on all nucleated cells and present exclusively to killer T-cells – a type of T-cell which can induce apoptosis of the cell. Class II on the other hand are mainly present only on antigen-presenting cells and interact with helper T-cells’ TCR to induce proliferation and further differentiation of T-cells and in turn B-cells (another type of lymphocyte that produces antibodies).
Relating back to the T-cell CD4/CD8 selection process, after being produced from bone marrow stem cells, lymphoid progenitor cells (the early form of T-cells) lack the TCR and contain neither CD4 or CD8 – termed ‘double negative’. As they mature and differentiate in the thymus to immature thymocytes, the progenitor cells start expressing the TCR, CD4 and CD8 and the cell becomes what is called ‘double positive’. From here is where the cells undergo selection in a process called positive selection. If the thymocyte cells interact with cells with Class I MHC on their surface, they become CD8 positive whilst if the thymocytes interact with Class II MHC presenting cells they become CD4 positive – in both cases they will lose the opposing co-receptor. If any cell interacts too strongly or weakly with the MHC, they will be removed. Cells which interact with self-MHC proteins are then removed to prevent the body attacking itself, which is termed negative selection – these process are visualised in the basic figure below The remaining cell become a competent T-cells which can be released from the thymus into the body.
When a mature T-cell binds to a MHC which is presenting foreign antigens, an intracellular signal will cause the T-cell to upregulate the synthesis of certain proteins called cytokines. Cytokines are molecules that induce the differentiation of T-cells and produce a variety of immune responses. Because of their importance and wide effects, they are tightly controlled and only certain cytokines are produced by specific subtypes of T-cell – for instance, the same type of CD4+ T-cell can produce helper T-cells 1, 2 and 17, due to different differentiation in response to different cytokines. The differentiated T-cells can go on to activate the antibody-producing B-cells and cause histamine production which are key to fight off invading pathogens.
While there is a ton of other interesting parts of our body’s immune system, I hope this brief overview of T-cells will have given you an small insight into the intricate workings of cell coordination in response to infection.
If you would like to read more about T-cells here is an in-depth review you may find interesting:
Figures made by myself and title picture taken from: http://www.pharmpro.com/news/2016/02/cancer-t-cell-therapy-safety-and-cost-concerns