CD4 and CD8
In order for activation to take place, a T cell not only has to bind to the peptide carried by a presenting cell (mostly dendritic cells), it also must attach to the MHC itself. This feat is accomplished by one of two proteins found on the surface of T cells. They're called CD4 and CD8. CD4 only fastens to MHC II molecules, and CD8 only to MHC I's. Both CD4 and CD8 help to hold the dendritic cell and T cell tightly together. In time, in the various lymph nodes throughout the body, the bond between these two kinds of cells increases even further as a result of the recruitment of additional co-stimulatory molecules. Their embrace groups the intracellullar parts of the T cell receptors, thereby initiating a cascade of chemical signals that ultimately gain access to the nucleus and cause the T cells to propagate, leave the lymph nodes, and perform their functions.
Just a few words about the nature of this "cascade". In a previous post in conjunction with a discussion of complement, I discussed proteolytic cascades, where one protein cleaves an inactive target, thereby turning it into an active proteolytic enzyme. In turn, this newly activated enzyme goes on to perform the same operation on a downstream protein. and on and on. The cascade that is initiated by activation of T cells operates in a similar manner, but instead of sequential proteolysis is makes use of successive phosphorylations. It turns out that many proteins can be controlled by the addition and removal of phosphate groups. These act as kind of on/off switches. The enzymes that perform the addition of the phosphates are called "kinases". In the T cell activation cascade, one inactive kinase gets a phosphate added, thereby becoming active. In turn, the newly awakened kinase adds a phosphate to another inactive enzyme, turning it on. And so on. Such phosphorylation cascades are very commonly used when a cell needs to transmit a signal from its exterior to its nucleus. In this way, it can respond to external events by switching appropriate genes on and off.
Most textbooks divide T cells into two major categories: helper and cytotoxic T cells. Cells with CD4 on their surface are destined to become helper T cells, while CD8 bearing cells become killers (I'll refer to cytotoxic T cells as killer T cells from now on. The name presents such a powerful image I just can't resist. Other names that these cells go by include CTL's and CD8+ cells. However, don't confuse killer T cells with natural killer cells that are part of the innate immune system).
Killer T Cells
Once activated, killer T cells and helper T cells have different missions. Killer T cells, after they have undergone many rounds of proliferation, move into the blood stream and search for cognate peptides presented on MHC I proteins. Since virtually all cells have MHC I's, any cell infected by a virus will display viral peptides on its surface and be vulnerable to passing killer T's. Like natural killer cells and professional hit men, killer T cells destroy their victims neatly, without leaving a mess and without too much collateral damage. They cozy up to their targets and inject special enzymes through the cell membrane into their quarry's cytoplasm, causing the victim to commit suicide (apoptosis). Alternatively, receptors on their surface can bind special proteins on the surface of their targets that in turn will elicit a suicide response.
Helper T Cells
CD4+ helper T cells play a more complicated role. They secrete a variety of cytokines that instruct other cell types, B lymphocytes, other T cells, macrophages, and dendritic cells, on ways to fight infection. There are three major types of helper T cells: Th1's, Th2's, and Th17's, each of which secretes a different spectrum of cytokines, and each of which is specialized to combat different foes. For example, Th1 helper T cells secrete a variety of cytokines that activate macrophages, which, in turn, gobble up cells infected with intracellular pathogens. In addition, they interact with B cells, causing them to switch to making IgG antibodies. Th2 helper cells, which master in the ability to defend against parasitic attacks, secrete other cytokines that among other effects, causes class switching in B cells to IgE. Th17's, only recently discovered, seem to focus on fungal invaders.
Remarkably, it turns out that the helper T cells are instructed to assume their various roles by dendritic cells. The numerous receptors that I previously described in the innate immunity section that are located on dendritic cells cause them to secrete specific cytokines appropriate to the triggering pathogen. In turn, these cytokines cause the helper T cells to become committed to one or another of the tracks described above.
After T cells have been activated they proliferate and go off to do their job. After their mission is completed, most get no social security or pension and just wither away via apoptosis. A fraction remains in the site where they first encountered the invader. If another pathogen of the same kind infects again, they are already activated and resume their attack Another fraction of activated T cells take up residence in lymph nodes. If they encounter the same invader again, they are much more readily activated than naive T cells, and seek out their quarry with increased efficiency. This immunological "memory" is one of the hallmarks of the adaptive immune system.
That's it. That's what I've learned about the immune system. Of course, all the information that I've covered is just a tiny fragment of what is known. But still, it's a lot to learn and remember. I'll present a brief overview in the next post. After that, I'll begin a discussion of cancer and the immune system response.