Immune System 101: The Effects of CLL
Last month's article in our immune system series covered the development of CLL and how it is diagnosed. Refresh your memory through the links in the left sidebar.
Once a diagnosis of CLL is confirmed, doctors look at additional factors to determine its probable course. Doctors once thought that all CLL cases were the same. They now understand that CLL can take different directions. Prognostic markers shed some light on the probability of an individual patient's disease course.
Current standard prognostic factors include Binet and Rai staging, lymphocyte doubling time, beta-2 microglobulin, thymidine kinase, FISH, IgVH mutation status, ZAP70 and CD38. Click here for detailed information on these factors.
CLL disturbs the immune system regardless of a patient's disease course. Some patients are affected more than others. B-cells are immune cells that develop into plasma cells which produce antibodies. As we have previously discussed, CLL cells are malignant B-cells which do not produce effective antibodies. (Immunoglobulin is the scientific term for antibody. You may come across this term in CLL Global articles or other sources.)
A normal B-cell goes through several stages of development before maturing into an antibody-producing plasma cell. Most CLL cells get caught in an intermediate stage of development. Additionally, CLL cells do not die as rapidly as normal B-cells. As a result, the CLL cells crowd out other cells in the lymph nodes and other organs. This is why some patients experience swollen lymph nodes; however, this is different from the swollen lymph nodes we experience when we are sick which eventually reduce to normal size.
Normal B-cells and plasma cells mass produce when needed to fight infection. Most of the fighting takes place in the lymph nodes. As the battle winds down, the cells die off. CLL cells also increase in number to fight infection. The CLL cells do not realize that they are malignant cells. Because they are stuck in an intermediate stage of B-cell development, they cannot produce antibodies and do not provide an effective immune defense. And because they resist programmed cell death, the lymph nodes remain enlarged.
In order to understand why CLL cells disrupt the immune system we must understand the role of antibodies which are a critical component of the immune defense. Antibodies are Y shaped proteins that have two main parts: the constant and the variable regions. The variable region differs in shape so that specific antibodies fit specific antigens, like a puzzle.
Antibodies can be created on the spot by a B-cell when a new invader enters the body. Once an antibody has been created, there is always a stash floating freely throughout the body. This way the immune system can more effectively fight antigens, or foreign invaders, it has already encountered.
When an antigen and an antibody meet, the antibody docks to the antigen and sends a signal to the immune system. The signal does two things: 1) More of the same antibodies are produced by plasma cells which attach to the antigen(s), and 2) Immune cells called phagocytes respond to the signal and "eat" the antigen that has been tagged by antibodies.
With less-than-normal levels of healthy B-cells, and subsequently antibodies, a CLL patient is more prone to infections. Next month's article on CLL and the immune system will include details about antibodies and IVIG (intravenous immunoglobulin) therapy which is given to patients as an antibody supplement.