Research Frontiers in Immunology
Scientists are now able to mass-produce immune cell secretions, both antibodies and lymphokines, as well as specialized immune cells. The ready supply of these materials not only has revolutionized the study of the immune system itself but also has had an enormous impact on medicine, agriculture, and industry.
Monoclonal antibodies are identical antibodies made by the many clones of a single B cell. Because of their unique specificity for different antigens, monoclonal antibodies are promising treatments for a range of diseases. Researchers make monoclonal antibodies by injecting a mouse with a target antigen and then fusing B cells from the mouse with other long-lived cells. The resulting hybrid cell becomes a type of antibody factory, turning out identical copies of antibody molecules specific for the target antigen.
Mouse antibodies are “foreign” to people, however, and might trigger an immune response when injected into a human. Therefore, researchers have developed “humanized” monoclonal antibodies. To construct these molecules, scientists take the antigen-binding portion of a mouse antibody and attach it to a human antibody scaffolding, greatly reducing the foreign portion of the molecule.
Because they recognize very specific molecules, monoclonal antibodies are used in diagnostic tests to identify invading pathogens or changes in the body’s proteins. In medicine, monoclonal antibodies can attach to cancer cells, blocking the chemical growth signals that cause the cells to divide out of control. In other cases, monoclonal antibodies can carry potent toxins into certain cells, killing the dangerous cells while leaving their neighbors untouched.
Genetic Engineering
Genetic engineering allows scientists to pluck genes—segments of DNA—from one type of organism and combine them with genes of a second organism. In this way, relatively simple organisms such as bacteria or yeast (a type of fungus) can be induced to make quantities of human proteins, including hormones such as insulin as well as lymphokines and monokines. They can also manufacture proteins from infectious agents, such as the hepatitis virus or HIV, for use in vaccines.
Gene Therapy
Genetic engineering also holds promise for gene therapy—replacing altered or missing genes or adding helpful genes. One disease in which gene therapy has been successful is SCID, or severe combined immune deficiency disease.
SCID is a rare genetic disease that disables a person’s immune system and leaves the person unable to fight off infections. It is caused by mutations in one of several genes that code for important components of the immune system. Until recently, the most effective treatment for SCID was transplantation of blood-forming stem cells from the bone marrow of a healthy person who is closely related to the patient. However, doctors have also been able to treat SCID by giving the patient a genetically engineered version of the missing gene.
Using gene therapy to treat SCID is generally accomplished by taking blood-forming cells from a person’s own bone marrow, introducing into the cells a genetically changed virus that carries the corrective gene, and growing the modified cells outside the person’s body. After the genetically changed bone marrow cells begin to produce the enzyme or other protein that was missing, the modified blood-forming marrow cells can be injected back into the person. Once back inside the body, the genetically modified cells can produce the missing immune system component and begin to restore the person’s ability to fight off infections.
Cancer is another target for gene therapy. In pioneering experiments, scientists are removing cancer-fighting lymphocytes from the cancer patient’s tumor, inserting a gene that boosts the lymphocytes’ ability to make quantities of a natural anticancer product, then growing the restructured cells in quantity in the laboratory. These cells are injected back into the person, where they can seek out the tumor and deliver large doses of the anticancer chemical.
Immunoregulation
Research into the delicate checks and balances that control the immune response is increasing knowledge of normal and abnormal immune system functions. Someday it may be possible to treat autoimmune diseases such as systemic lupus erythematosus by suppressing parts of the immune system that are overactive.
Scientists are also devising ways to better understand the human immune system and diseases that affect it. For example, by transplanting immature human immune tissues or immune cells into SCID mice, scientists have created “humanized” mice, a living model of the human immune system. Scientists are manipulating the immune system of humanized SCID mice to discover ways to benefit human health. Humanized mice are also being used in research on transplantation and autoimmune and allergic diseases, and to manufacture molecules that help regulate immune system function and immune tolerance.
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