What is a T cell?

A T cell is a type of lymphocyte that uses a receptor on its surface to recognize fragments of proteins (antigens) that are bound to a molecule called major histocompatibility complex (MHC). The 'T' in their name refers to the fact that they go through a selection process in an organ called the thymus early in their development. Selection occurs in two major steps in which the quality of the T cell receptor is tested by positive binding to MHC (positive selection), and subsequently tested for reactivity against self antigens (negative selection). T cells that bind self antigens too strongly create a risk of driving autoimmune diseases, so the result of negative selection is most often to kill the self-reactive T cell. However, some T cells escape the death process and instead are either programmed to be unresponsive (anergic) or they are educated to become suppressors or down regulators of the immune system. These 'regulatory' T cells (Tregs) are a very important source of protection from autoimmune diseases and other types of hyper immune reactions.

There are two major subsets of T cells that are distinguished by the types of antigen/MHC they recognize and their functions. Cytotoxic T lymphocytes (CTL) recognize antigens that are presented by Class I MHC, and T helper lymphocytes (TH cells) recognize antigens that are bound to Class II MHC. A T cell entering the thymus has the capacity to become either of these types of T cell, and the decision is based on interactions that occur during positive selection. When a T cell has a preference for binding to Class II MHC, then a second molecule known as CD4 also attaches to the MHC acting as an anchor to enhance the interaction. Conversely, binding to Class I MHC is anchored by a molecule called CD8, and when either CD4 or CD8 become activated on the T cell in the thymus, the expression of the other molecule is shut off. Thus, CTL are also known as CD8+ T cells and helper T cells are called CD4+ T cells, and these two markers can be very useful in identifying the type of T cells that are present in a sample. 

The two types of T cells have very different functions in the immune system. CD8+ CTL are specialized in recognizing antigens that come from the inside of a target cell. This is important for detecting viruses and bacteria that infect and live inside of cells. It is also a mechanism used to identify cancer cells that often have alterations in their intracellular contents. When CTL become activated by binding antigen on Class I MHC, their main function is to kill the cell with which they are interacting. CD4+ TH cells have a much more complex role that is worthy of a separate description, but suffice it to say for now that they are the major orchestrators of all immune responses. 

Autoimmunity...what is it?

When the immune system is reactive against something that is normally a part of the tissues of the body we call this "autoimmunity". When this reaction results in destruction of the cells or organs of the body to the point that the person is sick, it is called autoimmune disease. However, work like ours and that of others suggests that there is a very important role for autoimmunity, and a very important difference between it and autoimmune disease. It turns out that killer B cells and other specialized regulatory cells are often involved in autoimmunity as protectors. By being able to recognize self 'antigens' (see definition in earlier post), these cells go to sites in the body that need protecting, and by creating an immune suppressive environment there, are able to stop other cells from attacking the normal tissue. Mice that don't have these autoimmune regulatory cells are at a much higher risk of developing autoimmune disease, which is also something that happens in humans. One way that we hope to treat autoimmune diseases in the future is by boosting up the regulatory B and T lymphocytes, particularly the ones that have the correct self-reactivity that is specific to the disease being treated.   

What do killer B cells do?

A 'killer' B cell is so named because it has the ability to induce the death of another cell. In particular, these B cells are very good at killing another type of immune cell, the T helper cell, which is important because T helper cells are responsible for driving many types of autoimmune and allergic diseases. The way the B cell does this is by expressing a protein called Fas ligand that can bind to its partner Fas on the surface of a target cell. This binding, accompanied by other signals, sets off a cascade of events in the targeted cell that leads to changes in its internal structure and ultimately to the target cell imploding through a process called programmed cell death or apoptosis. One of the interesting things that we have found out is that the killer B cells not only can express Fas ligand on their cell surface, but they also make tiny vesicles that contain Fas ligand that have the potential to travel throughout the body looking for T helper cells to target. This is important because killer B cells are normally located in the lining of the intestines and in the lungs, where they are not likely to encounter their prey. Their location and other interesting aspects of their biology make it quite likely that killer B cells play an important role in reducing severe allergic reactions such as asthma and food allergy. There is also evidence that they are involved in tolerance toward self antigens and the suppression of autoimmune diseases such as rheumatoid arthritis and type 1 diabetes. We are working very hard to understand as much as possible about these unique cells, and in developing ways to use them as therapy for many types of diseases.

What is an antigen?

The term antigen refers to something that is recognized by the immune system. This can be something on the surface of a virus, a pollen grain, a toxin produced by a bacteria, or any number of other small molecules. Antigens can come from the environment and be foreign to the body, or they can be something that is normally produced by cells of the body. These latter antigens are called self antigens or autoantigens, and the response of the immune system against them is referred to as autoimmunity. 

What is a B cell?

B cells (aka B lymphocytes) are one of many types of cells in the immune system. There are many millions of them spread throughout the body. They are the only cells in the body that produce factors called antibodies (aka immunoglobulins) that do many important things. People with too few B cells or the antibodies they produce can have trouble defending against common microbes (viruses, bacteria, etc) and may get very serious and life-threatening infections.

Antibodies can bind to proteins and other biomolecules that are floating around in the body or that are attached to other cells. When each B cell develops, it makes a series of changes to its genetic code that end up producing an antibody with a random binding specificity. This makes every new B cell likely to recognize something different than every other B cell in the body. 

That's important because it leads to the total population of B cells being able to recognize almost any kind of protein or biomolecule in the world, including those that are on dangerous microbes that the person has never been exposed to before. When a B cell finds something that it recognizes through its surface antibody (aka B cell receptor) it can start to become activated.  

If B cells get activated, they can divide to form daughter cells with the same specificity leading to increased number of them. They can also make other genetic changes that allow their antibodies to leave the cell and spread throughout the rest of the body. This is the basis of how most vaccines work. By activating B cells that are specific toward the proteins on the particular microbe or factor (flu virus, measles virus, tetanus toxin, etc) that is being targeted by the vaccine, the immune system gets more prepared to recognize and eliminate those microbes and factors.      

What does the immune system do?

In the most simple terms, the immune system is your body's protection against being invaded by small creatures that would like to make you their home.

The truth is that it isn't all that simple, and in fact many bacteria, viruses and other microbes not only live in and on us, but they are very important to our health and well-being. There are trillions of these microbes in the body, mostly living in the parts that are exposed to the outside, like the gut, lungs, and skin. The good ones help us digest food and in their own way help the immune system to keep us protected from bad microbes. 

So the immune system actually chooses between leaving alone what seems to be harmless and violently attacking what might be very bad for you every second of every day. When it gets activated, the immune system has many specialized tools to fight the different kinds of invaders it meets. Some of these tools can be quite dangerous to our own bodies if they are not tightly controlled, and there are many additional ways in which the system regulates itself. 

For the most part, the system is very good at what it does and we don't even notice how busy it is keeping us safe. However, sometimes things go wrong, and that's when we get sick.   

Would you like to know more about the immune system?

Many of you may wonder how the immune system is supposed to work or why it sometimes doesn't do what it is supposed to do. In this space, we hope to be able to answer questions you may have in a clear and concise way. Please ask us using the comments box, and we will do our best to respond to you and others who may have similar questions. From time to time, we will also post general topics for those of you who would like to follow along.