EVEN my five year old nephew has heard of antibodies. But what are they?
They are protein molecules found in your bloodstream. Their function is to seek out foreign bodies such as viruses and bacteria and mark them for destruction. Hence the name "antibodies". The antibody army is a large one, with an estimated 100 million million million antibody molecules circulating in the body.
The shape of antibody molecules (also called immunoglobulins) is essential to the way they seek out alien invaders in the bloodstream. Their basic structure is often thought of in terms of the shape of the letter Y. The two arms of the Y are identical. Each is able to attach to the foreign invader, which is now called an antigen. The stem part of the Y interacts with the rest of the body's immune system, which results in the destruction of the foreign body.
Although all antibodies have the same basic structure, they can combine to form larger molecules that each perform slightly different jobs (see diagram). The mainstay of the antibody army is the single Y molecule, called IgG (meaning immunoglobulin G). Another single Y molecule is called IgE. IgE has a special function in helping to combat parasitic infections. These have gained much attention because of their link with allergic responses.
IgA molecules are made up of two Ys linked tail to tail. These are important in protecting the external linings of the body, most importantly, the lungs and the alimentary canal. The biggest Ig molecule is IgM. Here, five Ys join in a ring structure. These are produced early in the body's response to infection, and are weaker than the IgG molecules produced later. The presence of 10 places at which to attach to the enemy invader helps to compensate for this weakness.
So how do these molecules seek out enemy invaders and go about having them removed, and how can they tell whether they are enemy invaders or not?
Although the basic structure of each antibody is the same, the areas at the tips of the Y arms are different from one antibody to the next. Each antibody is produced by a different antibody producing cell called a B cell.
It is reckoned the body can generate more than 100 million different antibody molecules in this way. These will all attach themselves to slightly different chemical structures, including those present in the body.
Early in human development, before birth, the immune system is in a learning mode. Protected by the mother's immune system, and so being free of any foreign bodies, the only molecules present are those of the growing infant. These are called "self" antigens.
Many of the antibodies produced will attach to these self antigens. These antibodies are then removed from the immune system, or rather the B cells that produce them are removed. All that should remain are B cells that produce antibodies to molecules not already present in the body. This still leaves many millions of combinations that can seek out and bind to antigens present on viruses, bacteria and parasites. The immune system is now ready to take on all comers. However, it still has a lot to learn.
If the body becomes infected with, for example, a bacteria it has never encountered before, then somewhere in the immune system there is an antibody, or even several antibodies, that can bind to it. These could be spread out through the blood stream and lymphatic system.
Lymph nodes are like busy market places for cells of the immune system. Here, many B cells can come into close contact with other immune cells, along with the invading bacteria. In this way, the bacteria has more chance of coming into contact with B cells that produce antibodies which can attach to it.
When this happens, the B cells producing these antibodies multiply rapidly and produce more antibody against the bacteria. So, often the first sign of infection can be the swelling of lymph nodes due to this extra activity. Most people are familiar with the swelling of their tonsils in response to an infection.
The antibodies produced at this early stage do not bind to the foreign body that strongly, so IgM molecules are used which can bind at 10 sites per molecule. In the meantime, the B cells undergo further changes that "fine tune" the structure of the antibody so as to bind more and more strongly to the foreign antigen. This strength of antibody binding is called affinity.
Eventually, the low affinity IgM molecules are replaced by high affinity IgG molecules. To become active, these IgG molecules must attach at both arms. This then allows the stem of the antibody to attach to other cells and molecules of the immune system.
One important set of such molecules is called "complement". The binding of the antibody to the bacteria causes a series of changes in the complement molecules, one result of which is the Membrane Attack Complex, where a hole is formed in the membrane of the bacteria, allowing its contents to spill out and be destroyed. Many other cells also attack foreign bodies such as cytotoxic T cells (Tc) which recognise antigen, and natural killer (NK) cells which recognise the stem part of the antibody that is bound to antigen. These produce cocktails of enzymes that can also attack and break down bacteria and parasites.
If the immune system wins the battle, all the foreign invaders are destroyed. Many of the B cells that produced the antibodies now go on to form memory cells.
UNDERSTANDING the workings of the immune system allows us to go one step further and prevent the body from ever having to suffer a disease. This is the principle of vaccination. Here, the body is allowed to encounter the enemy on safer territory. In the case of viral immunisations, such as the measles, mumps and rubella viruses (MMR), the body is supplied either with virus that has been killed or virus that has been severely disabled, so making it incapable of causing disease. Antibodies are still produced against it, and this results in subsequent resistance to disease.
Our immune system is complex, and much of it remains undiscovered and poorly understood. Such complexity also leads to fallibility, and the immune system can fail to function in many ways. Many of these relate to how the antibody carries out its functions. In these instances, the antibody is guilty of treachery, turning on the body and inflicting damage.
Disease brought about by the failure of anti bodies to function correctly can be broadly categorised into two groups, between which there is considerable overlap. These are hypersensitivity and auto immunity. The most common form of hypersensitivity is that of the allergic reaction. Most allergies are against substances in the environment that are of little or no harm, such as pollen, dust, penicillin and nut oils. The immune system, for reasons that are poorly understood, designates these as dangerous foreign invaders and mounts and immunological attack against them. In these cases the allergic response is led by IgE antibodies.
These are powerful activators of immune cells called mast cells. These cells are stimulated to release powerful and last acting chemicals such as histamines, heparin, and prostaglandins.
These bring about an immediate and extreme inflammatory response. In hay fever, the symptoms are runny nose, streaming eyes, itching, etc. This response is quite localised and not life threatening.
Many people are also allergic to the dust mite, or rather its faeces. When these enter the lungs in airborne dust, an asthmatic response may result which inflames the airways, restricting breathing. The Asthma Society of Ireland estimate that 250,000 Irish people have asthma. The incidence is much higher among children, where one in seven is thought to be affected, compared with one in 20 adult sufferers.
Other more severe allergic responses are against antigens such as bee venom, certain nut oils and penicillin.
It is not yet clear why the body decides to make IgE antibodies to substances such as pollen, penicillin and nut oils, and not to other substances in the environment, or more importantly, why it makes them at all.
Antibody soldiers are very powerful and have at their disposal the considerable resources of the immune system. This gives them the strength to defend us from very many bacteria, viruses and parasites. They do, however, carry a double edged sword, which, when turned upon the body can inflict considerable damage, and even kill.
Research in immunology is some of the most exciting and fast moving in modern science. The untold complexity of the immune system ensures this will be a long task. As more becomes known, however, ways of directing the immune system to even greater good will be discovered.
One such exciting area is the immunotherapy of many cancers. Further knowledge of the immune system will no doubt help us in the fight against many diseases. This knowledge will also show why the immune system sometimes turns on itself, causing what seems to be needless self destruction. In understanding this, even better cures for auto immune diseases such as rheumatoid arthritis, myasthenia gravis and multiple sclerosis will inevitably follow. We wait.