A BRIEF INTRODUCTION TO IMMUNOLOGY

You may wonder what the connection is between the findings in ALPS and the immune system. To understand what happens in ALPS, we would like to review some basic information about the immune system. It is the immune system that defends our bodies against germs. There are many components of the immune system. Two major components are the spleen and white blood cells. The spleen is a fist-sized organ found to the left of your stomach. It has a special job of filtering the blood, by cleaning out dead blood cells that aren't needed any more. The blood contains many types of cells:

• red blood cells help transport oxygen to your tissues
• platelets help to form blood clots
• white blood cells are the soldiers in your immune system.

One major class of white blood cells is called lymphocytes. There are many kinds of lymphocytes to combat the variety of germs in the world. B cells and T cells are two major kinds of lymphocytes.

There are many kinds of T cells. Some of these direct our immune response to infections, and others kill infected cells. Each T cell is named for the markers found on its surface. There are over 100 different markers. For example, some T cells are called CD4 cells because they have the type 4 chemical marker coating their surfaces. Other T cells are named CD8 cells because they are coated by the type 8 marker. Almost all T cells of healthy people have either the type 4 or the type 8 marker. Those with neither type 4 nor type 8 markers are called double-negative T cells. People with ALPS often have increased numbers of double-negative T cells.

People with ALPS often have extra B cells, too. The B cells produce immunoglobulins (Ig's, also called antibodies). The antibodies are custom-fit to stick to specific germs. There are thousands of different antibodies in the body. Each is molded for a specific germ. Because ALPS patients have more B cells than normal, they produce more antibodies, including ones that cause autoimmune problems.

WHAT HAPPENS IN ALPS

To better understand how ALPS works, imagine that you have a respiratory infection, perhaps the flu. The cells in the nose and throat send out a message to the immune system to start making more lymphocytes to fight the flu. New troops of lymphocytes come to the nose and throat to seek out and destroy the cells infected with the flu virus. Once the virus is conquered, the lymphocytes get a message that their job is done and they are no longer needed. At this point, it is normal for most of the fighter cells to disintegrate through a process called apoptosis (a-pop-to'-sis).

The immune systems of people with ALPS are efficient in fighting germs. The problem in ALPS happens after an infection is gone. In ALPS, apoptosis does not work as well as it should. In other words, the troops (lymphocytes) don't hear the message that the war is over. As a result, excess T and B cells gather in the lymph glands, liver and spleen. We can detect the extra cells in people with ALPS by looking for high numbers of double-negative T cells. In general, these extra T cells don't cause a problem.

Sometimes in ALPS, the B cells make a mistake. Instead of making antibodies to be custom-designed against germs, the B cells make antibodies against platelets, red blood cells, or other cells. This causes autoimmune problems. The antibodies become stuck to the platelets and red blood cells, which then get stuck in the spleen. The spleen has to work extra hard to filter out the sticky cells. This is another reason why the spleen gets so big.

http://www.niaid.nih.gov/publications/alps/alps.htm#a

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