The Immune System
Part of A Practical Guide to HAART (Highly Active Anti-retroviral Therapy)
The immune system is the body's defense against disease. It defends the body from attack by foreign invaders such as bacteria, viruses, fungi and parasites, as well as cancerous cells.
Normally, the immune system can distinguish between what belongs in your body (self) and what doesn't (non-self). It is able to remember previous encounters with foreign invaders and to defend itself. For example, if you had measles or chicken pox as a child, your immune system should remember the organisms that caused these diseases, and during any future encounter will respond to them in a way that is effective in preventing you from again developing those diseases.
The skin is the first line of immune defense. It provides a physical barrier to keep bacteria and viruses from getting inside the body. The mucous membranes that line the body's entrances (such as the mouth, nose, rectum, vagina and penis) and passages (such as the throat and windpipe) form another barrier.
When disease-causing germs (also referred to as pathogens or microbes, including bacteria, viruses, parasites and fungi) get past these outer barriers, the internal part of the immune system comes into play. The immune system's job is to recognize what belongs in the body and attempt to get rid of what doesn't, or at least suppress it so it won't cause harm. The major parts of the immune system include the bone marrow, the thymus, the lymph nodes, the spleen, and the mucosal-associated lymphoid tissue (MALT), which includes the tonsils, the appendix, the Peyer's patches on the outer wall of the intestines, and the lymphoid cells in the inner part of the intestines.
The lymphatic system is made up of vessels -- just like the veins, arteries and capillaries that carry blood -- that branch out into all parts of the body. Instead of blood, these vessels carry a clear, watery fluid called lymph. This fluid carries foreign material away from your body's cells. The lymphatic vessels pass through small bean-shaped tissues called lymph nodes. The lymph nodes trap, filter and destroy foreign material, including bacteria, viruses and other microbes.
There are 500 to 1,000 lymph nodes scattered throughout the body. Large groups of lymph nodes are found in the neck, armpits and groin. Sometimes when you have an infection you can feel what people often call "swollen glands" in your neck. These are not actually glands at all, but rather your lymph nodes responding to the unwanted germs.
Each lymph node is densely packed with millions of immune cells that identify and destroy the microbes that cause disease. These infection-fighting cells are known as white blood cells or leukocytes, and they are the fundamental players in your cellular immune response. Although they are called white blood cells, only about 2% of these cells actually circulate in the bloodstream, with the rest found in the lymphatic system.
There are many different kinds of white blood cells, including dendritic cells, granulocytic cells (neutrophils, basophils and eosinophils), mast cells, megakaryocytes, mononuclear cells (monocytes and macrophages). The ones most affected by HIV are the lymphocytes.
Lymphocytes are very important immune cells. At any given moment, a healthy person has about one trillion lymphocytes in the body. Below is some information about key lymphocytes and macrophages, another group of cells that are strongly affected by HIV disease:
B cells are lymphocytes which make and release antibodies. These are proteins that can lock on to bacteria or viruses. When an antibody locks on to a germ, it acts as a signal for other immune cells to destroy the invader. Each B cell is programmed to make one specific antibody. For example, one B cell will make the antibody that blocks the common cold virus, while another makes an antibody that locks on to the bacteria that cause pneumonia. Antibodies are generally not useful in fighting HIV.
T cells are lymphocytes which carry out a number of different functions, depending on their type. The different T cells can be identified by proteins, called receptors, on their surfaces.
CD4+ cells are T cells that have a protein called CD4 on their surface (also referred to as CD4 positive or helper T cells or T4 cells). CD4+ cells lead the attack against infections. They release chemical messengers called cytokines that stimulate other immune cells to make antibodies or to destroy infected cells. CD4+ cells are sometimes compared to the quarterbacks on a football team or the conductors of an orchestra, because they direct the body's immune response.
CD8+ cells are T cells that have a protein called CD8 on their surface (also referred to as CD8 positive). CD8+ cells which recognize a specific antigen (like HIV) differentiate into what are called cytotoxic T lymphocytes (CTLs), often referred to as killer T cells (but not to be confused with natural killer cells, discussed below). These CTLs monitor the cells of the body and kill altered cells (such as virus-infected or cancerous cells) or stop them from producing HIV.
Natural killer (NK) cells are lymphocytes which kill virus-infected and cancerous cells, both in response to CD4+ cell signals and on their own, without direction from other lymphocytes. NK cells are important in the regulation of lymphocytes and other immune cells and, although they have been far less studied by AIDS researchers, may contribute substantially to the body's suppression of HIV. It is thought that they work to check the spread of infection by destroying HIV-infected cells; they also kill opportunistic virus-infected and cancerous cells.
Macrophages are a group of immune cells that perform many functions, including warning the immune system about invading microbes and helping to attack and destroy HIV-infected and cancerous cells. Macrophages can be infected with HIV, and HAART does not work well in HIV positive macrophages. Researchers are trying to design new drugs that can work in them.
In a nutshell, HIV prevents the immune system from working properly. When it infects and destroys CD4+ cells, their ability to direct the body's immune response is compromised. Although the body fights this by constantly producing new cells -- up to 2 billion new CD4+ cells daily -- over time the virus tends to win out, with the body becoming less and less able to suppress HIV. In addition, as the immune system becomes ever more dysfunctional, the body may become unable to control the organisms that can ultimately cause potentially fatal opportunistic infections. It may also have less ability to control the spread of cancerous cells.