September 18, 2008
The immune system is a complex network of cells and chemicals. Its mission is to protect us against foreign organisms and substances. The cells in the immune system have the ability to recognize something as either "self" or "invader," and they try to get rid of anything that is an invader. Many different kinds of cells, and hundreds of different chemicals, must be coordinated for the immune system to function smoothly.
The immune system can mount a variety of responses to attack specific invader organisms. One of these responses is coordinated by T-helper cells (also known as T cells, T4 cells, or CD4 cells), which act as a kind of orchestra conductor. The T-helper cells tell other cells what to do when this response is triggered. We are interested in this immune response because it is the one that is most disrupted by HIV infection. As HIV succeeds in destroying more and more of these important cells, the ability to fight off other infections gradually declines. If the "coordinator" of the process, the T-helper cell, is no longer functioning, other cells in the immune system cannot perform their functions, leaving the body open to attack by opportunistic infections.
Let's look first at how the immune response coordinated by the T cells is supposed to work. Please keep in mind that we will be explaining only one of the body's immune responses.
Any infectious agent (Figure 1) that enters your body will eventually be taken up in your lymphatic system.
This may happen very soon after infection, or it may not happen until the invader has found a niche and begun to replicate. In one of your lymph nodes, the infectious agent (which we will call "Virus" in the figures) will bump into a macrophage (literally "big eater"). The macrophage will ingest the invader (Figure 2).
Then the macrophage takes the invader apart and displays the viral antigens on its surface for other immune cells to read (Figure 3).
Antigens are proteins specific to each particular microorganism. The antigens act as an identity card that allows our immune system to recognize invader organisms that need to be eliminated.
After displaying the agent's antigens, the macrophage will send out a message to a T-helper cell to read and recognize the antigens (Figure 4).
This message activates T-helper cells and triggers the immune response. Once the T cell has read the antigens, it will send out messages to activate other cells, known as B cells (Figure 5), which will in turn come and read the antigens from the macrophage's surface (Figure 6).
The activated B cell will then produce millions of antibodies (Figure 7). The antibody is a protein that will bind to an antigen. Each antibody is unique and specific; for example, a measles antibody will only bind to a measles virus. We produce antibodies because, given the high concentration of infectious agent that is needed to cause disease, our macrophages could not go after the invaders alone. However, antibodies can outnumber the invaders and help us get rid of them.
How do the antibodies bind to the infectious agent? The antibody resembles the mirror image of the antigen (like a key and a lock), usually providing such a close fit that, if they bump into each other, the antibody will grab the antigen and hang on (Figure 8). Once an antibody has "caught" an invader, it will broadcast a signal that says "eat me and whatever I have captured" (Figure 9). A macrophage will in turn get the message and will devour the antibody-antigen complex and rid the body of the infectious agent (Figure 10).
Eventually, as this process continues, the number of infectious agents will decrease and the body will need to stop the battle. However, all the cells are still activated and the immune system needs to put them to rest. Another kind of T cell, the T-suppressor cell (or T8 cell), will send out messages to the other cells and "de-activate" them (Figure 11). Without the T-suppressor cells, the body would continue trying to fight off a disease that no longer exists (and eventually would end up fighting its own cells).
With HIV infection, this procedure does not work adequately. Initially, macrophages recognize the HIV, T-helper cells initiate the response, and B cells produce antibodies. However, although effective at first, the antibodies do not eliminate the infection. Although some HIV might get killed, many more viruses will actively infect T-helper cells -- the very same cells that are supposed to coordinate the defense against the virus. Infected T cells become virus factories which, if activated, will produce more copies of the virus instead of triggering the production of more antibodies against HIV.
Besides T cells, HIV is capable of infecting other cells (e.g., macrophages, B cells, and monocytes) and can cross the brain-blood barrier, infecting nervous system cells. Most immune cells cannot cross that barrier, which surrounds the brain and spinal cord, so HIV can retreat where the immune system cannot follow.
The immune system is very complex and many of its processes are still not understood. This brief explanation of the immune response coordinated by the T-helper cells will help you understand issues surrounding immune monitoring and treatment for HIV disease. Some of the tests that are used to monitor the health of HIV positive people show how well the immune system is working (e.g., T cell or CD4 cell counts), while others show the number of copies of the virus in the body (viral load). Monitoring and early treatment can be crucial in determining the course of HIV disease and making informed choices about treatment.