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Yuta Asano, a Ph.D. student at University of Chicago

What is an Antibody? (an image from Asano's presentation)
11th Japanese Researchers Crossing in Chicago Presentations (2):
What is Immunity?
What is an Antibody?

• The 11th Japanese Researchers Crossing in Chicago featured a presentation, “How an Antibody Works,” by Yuta Asano, a Ph.D. student at University of Chicago, where he explained the basics of the antibody’s structure and functions.

• Our body takes in thousands of viruses and bacteria as we breathe, and harmful ones must be distinguished and handled one way or another. Immunity is a function of our body to protect and keep us healthy, and the antibody is a primary weapon used in that function.

• An antibody is in a shape of a Y and created by a cell called “B cell.” When antigens such as bacteria or viruses enter our body, antibodies bind to them and flag them for other immune cells as targets so they can gather around and destroy the antigens. It is the important function of antibody to recognize and distinguish foreign substances that enter the body.

• The antibody is unique in that one B cell produces only one kind of antibody which recognizes only certain types of antigens. For example, an antibody that binds to a bacterium can’t bind to a virus and vice versa, and only one kind of bacterium or virus at that. This means that as many antibodies are needed as there are bacteria or viruses. However, there is only one human gene that produces an antibody.

• How, then, does our body fight numerous kinds of antigens? The answer is in the B cell, which randomly recombines genes from three gene segments (V, D and J) and creates a wide variety of new genes. Not only the recombination occurs randomly but mutation can also occur randomly at the time of recombination. As a result, each B cell can produce many different antibodies. “Theoretically, an infinite number of antibodies can be created, and that’s what we are fighting our enemies with,” Asano said. This mechanism was discovered by Professor Susumu Tonegawa, who was awarded the Nobel Prize for Physiology or Medicine in 1987.

• Use of Antibody (1): Cancer Treatment

• It is extremely difficult to create a drug that targets only the cancer cells because of the fact that they are a physical part of the body. The existing cancer drugs, designed to target fast-growing cancer cells, have side effects of hair loss, bloody coughs, etc. because the cells that make hair, cuticle of the wall of digestive tract, etc. also grow fast. Cancer cells normally involve some kind of mutation, and they often secrete protein that other cells do not produce. Antibody drugs are the drugs that are designed to target such unique proteins by using the antibody’s characteristics of binding only to specific substances.

• Herceptin is one of the most famous antibody drugs that are used to treat cancer. It is designed to target the protein called HER2 that is secreted in large amount from breast cancer cells. The drug’s antibody is made to recognize that protein so that it will bring in other immune cells to destroy the cancer cells. Patients who show HER2 production have a low rate of survival, but when Herceptin was used, the recurrence rate went down by 50% and the survival rate after 3.5 years increased to 90%. Approved by the Food and Drug Administration in 1998, Herceptin is the world’s first antibody drug. Due to its high rate of success, a film (“Living Proof”) was produced depicting the drug.

• Uses of Antibodies (2): Imaging

• When researchers want to see where a specific protein is located within a cell, they first color the antibody that is a match to that protein. This way, they can tell where the protein is by the colored antibody which binds to that protein. This is the method which is widely used among researchers. One example of this “imaging” is the visual observation of the cuticle of the intestinal tract, which is made up of slippery membrane. This membrane serves as a barrier between the intestinal tract cells and bacteria. We can see how it works by using the antibody imaging method.

• When an Antibody Works Against Us

• While an antibody recognizes what is alien, something alien and something harmful is not always the same. When an antibody recognizes innocuous substances such as food and pollen as harmful, it causes a condition called allergic reaction.
• When B cells mistakenly create antibodies against certain foods or pollens, special cells called “mast cells” that are often located in membrane “catch” the antibodies. When pollens or any other antigens reach the mast cells, the latter get activated and produce chemical substances such as histamine, which causes sneezing, runny nose, watery eyes, etc.

• Autoimmune Diseases

• While B cells create antibodies through random gene recombination, we don’t know what each antibody is created against; some of them could even create antibodies against its own body. Even though B cells are carefully controlled against that by the entire body system, sometimes it happens, and when runaway B cells get activated, it causes sickness. The condition caused by the immune system going into disarray and attacking its own body is called autoimmune disease. Such diseases include collagenosis, joint rheumatism, a special kind of diabetes among thin people (where antibodies attack the insulin-producing cells) and Braves’ disease, among others.

• Cells like B cells that recognize its own body are being created within our body regularly. In the case of an average healthy person, about 20% of the B cells in the body have a potential to attack their own body, Asano said. One of the autoimmune diseases, SLE (systemic lupus erythematosus), is a condition where immune cells mistakenly attack healthy tissues of various internal organs. Asano’s laboratory primarily studies SLE in kidneys (lupus nephritis).

• Lupus nephritis has a high degree of finding among SLE cases and about 50% of the patients develop kidney failure in five years after the first diagnosis, but the treatment hasn’t much changed in the past 30-40 years. Asano explained that his laboratory is working hard to establish the method of surer diagnosis and better treatment. In addition, they are getting closer to understanding which immune cells are producing antibodies against which antigens, Asano said.