Biomedical Engineering

I was very surprised to learn today that doctors and scientists didn't (until this month) know how antibodies really worked. Antibodies have been a common medical treatment for 70 years and have been cures for common and not so common diseases. With the ever increasing list of antibody resistant drugs, it's important to understand how and why antibodies work.

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Antibodies are produced by plasma cells (a kind of white blood cell) and found naturally in the blood and in body fluids such as gamma globulin proteins. Also known as Immunoglobulins (Ig), antibodies are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. The structure of an antibody consists of two large, heavy chains and two small light chains to form monomers with one unit, dimmers with two units, or pentamers with five units. While the general structure is similar, there is a small region at the tip of the protein which changes to allow the antibody to recognize a wide variety of antigens. The unique tip means that the antibody will only respond to that antigen in a highly specific interaction, called induced fit.

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Antibodies can either "tag" the antigen for attack by other cells in the immune system or it can attack the target directly. A new study, published in Science, explains how the antibody is able to attack and kill the invading bacteria. A previous study done in 2007 by James Collins identified three classes of antibodies: quinolones, beta-lactams, and aminoglycosides. These three classes kill cells by producing highly destructive molecules known as hydroxyl radicals. Hydroxyl radicals are highly reactive and react with almost everything in the body, but they generally do not cause damage--except to the DNA of bacteria. Hydroxyl radicals induce damage to guanine (for those who don't remember middle school science, because I sure didn't, guanine is a nucleotide base that constitutes DNA). As the damaged guanine tries to reinsert itself into the bacteria's DNA for repair, it ends up hastening its own death.

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The oxidized (damaged) guanine is used as a building block to DNA synthesized by a special DNA copying enzyme called DinB. Bacterial cell death occurs because DinB not only inserts the oxidized guanine with its correct base pair cytosine, but also with adenine. When too many oxidized guanines have been inserted into new DNA strands, the cell tries to remove the lesions. The unsuccessful efforts to remove the lesions results in death as the double helix breaks from too many repairs happening at the same time.

Understanding how antibodies work could help scientists improve existing drug, reduce the required doses and resensitize strain to existing antibiotics.

References

Pinpointing how antibiotics work

Antibody-What is an Antibody?

Study Reveals How Antibiotics Work