Antibodies: The good, the bad, and the ungainly

When we catch the flu, our body makes antibodies against the flu virus. When we get a bacterial infection, our body makes antibodies to fight the bacteria. In fact, whenever any foreign substance – an antigen – manages to enter our body, we make antibodies to destroy it before it can do us permanent harm. (But we tolerate food! Thank goodness for that.)

Antibodies are a major component of our immune system. They are proteins that are designed to be good binders of all sorts of (big) molecules. When an antigen gains entry into our body, before long our immune system will have produced antibodies specific for that antigen and able to bind to it very tightly. Further, the binding of antibodies to an antigen brings into the fray other components of our immune system – cellular as well as other molecular components – and together they bring about the neutralization, destruction, and elimination of the foreign substance. Furthermore, the cells and molecules of our immune system are constantly on patrol, making sure that our body is free of germs and other harmful agents. They are also on the lookout for our own cells that have become abnormal or have become infected by viruses or other pathogens; our immune system gets rid of those cells, too.

All the cellular components of our immune system, including the cells which will eventually produce our antibodies – the so-called B cells – originate in the bone marrow. After completing their differentiation in the bone marrow, the B cells migrate to the periphery (the blood and lymphatic system) to become the antibody-producing plasma cells. While still in the bone marrow, the B cells are screened for "self-reactivity," i.e. they are tested to see if the antibodies they produce bind to our own molecules. If they do, those self-reactive B cells do not leave the bone marrow – they die there. (You can imagine what havoc they would produce if a host of self-reactive antibodies is let loose in our body!)

There is a further safeguard against self-reactivity. During their development, the B cells are stimulated by "helper T cells" (cells that originate in the bone marrow but complete their differentiation in the thymus). In the thymus, the developing helper T cells (and other types of T cells) are likewise screened for self-reactivity and the self-reactive ones do not leave the thymus.

We then have an immune system whose components are ready to react to any pathogen, or harmful foreign substance, but not to our own molecules. Since we cannot know what sort of pathogens we will encounter on any given day, we produce millions of different B cells and T cells every day. Moreover, our immune system remembers. Memory B cells and memory T cells are produced so that we are ready to vigorously fight any pathogen that tries to invade our body a second time. We have a magnificent defense system.

But read on.

Sadly, our immune system is not perfect. Sometimes, antibodies and T cells (especially the killer type) are produced that do react to our own molecules. We then have what is called an autoimmune disease.

Some individuals, predominantly women, have antibodies to DNA or other components of the nucleus, which causes an autoimmune disease called Systemic Lupus Erythematosus (SLE). The antibody-antigen complexes resulting from SLE often clog up the kidneys and other organs of the body and could cause death. In individuals suffering from myasthenia gravis, there are antibodies that bind to the acetylcholine receptor and they interfere with the transmission of signals from nerve to muscle, causing muscle weakness. Some unfortunate individuals produce antibodies to their own antibodies and this causes rheumatoid arthritis. One form of diabetes is caused by the presence of killer T cells that attack the cells in the pancreas which produce insulin. These are just a few examples of autoimmune disease. There are many others, most of them caused by wayward antibodies.

And then there is allergy. Allergy is caused by IgE – a type of antibody – which is usually found on the surface of mast cells and basophils. Mast cells and basophils have granules filled with histamine and other vasoactive compounds. The binding of allergen (an antigen that causes allergy) to the IgE causes the release of the histamine and the other compounds, resulting in runny nose, sneezing, and other symptoms of allergy. Why do we have IgE when it seems that all it causes is misery (sometimes, even death in severe allergic reactions)? Well, it turns out that IgE affords protection against parasites. The world is cleaner these days and we have learned to cook our food well, so that not many of us harbor parasites anymore. But we all still produce IgE – just in case – and more and more of us are suffering from allergies.

In addition to autoimmunity and allergy, there are other disorders due to antibodies.

When protein molecules are not very stable, they could (partially) denature and aggregate, and the aggregates could clog up vital organs. Antibodies are no exception. With the millions of B cells generated every day, it is highly likely that unstable antibodies would be produced. Fortunately, if an antibody does not find an antigen to bind to, or is otherwise nonfunctional (which it would be if it is not stable), the antibody (or, more correctly, the B cell that makes it) is eliminated from the pool. However, there are diseases in which B cells (or plasma cells) become "transformed" and do not die — a cancer. If the antibody, or a part of it, that a transformed cell makes is unstable and has a tendency to aggregate, we have an additional disorder.

Antibodies are good. Without them, we will not last for very long. (We carry 10 times more bacteria, in us and on us, than we have cells in our body, and I shudder to think how many viruses are lurking inside us – all ready to pounce as soon as they sense that our immune system has weakened.) But, as you saw, antibodies can be bad, too. And the unstable ones cause more harm than good.

Eduardo A. Padlan has a Ph.D. in Biophysics and was a research scientist at the (US) National Institutes of Health until his retirement in 2000. He is currently an adjunct professor in the Marine Science Institute, College of Science, University of the Philippines Diliman. He is a corresponding member of the National Academy of Science and Technology, Philippines. He can be reached at [email protected].