Free in plasma; about 80 percent of circulating antibodies Surface of B cell; free in plasma
Surface of B cell
Monomer found in plasma; polymers in saliva, tears, milk, and other body secretions
Secreted by plasma cells in skin and tissues lining gastrointestinal and respiratory tracts
Most abundant antibody in primary and secondary responses; crosses placenta and provides passive immunization to fetus
Protects mucosal surfaces; prevents attachment of pathogens to epithelial cells
18.11 IgG Antibodies Promote Phagocytosis
When IgG antibodies cover a bacterium, receptors on a macrophage can recognize, bind to, and engulf it.
An initial challenge to scientists seeking to accomplish this was that the immune response to a complex antigen is not simple. Therefore, they could not simply produce antibodies by injecting an animal with the antigen they wanted to look for. Because most antigens carry many different antigenic determinants, animals injected with a single antigen will produce a complex mixture of antibodies, each made by a different clone of B cells. So the normal antibody response is said to be polyclonal.
Suppose that a woman is infertile and her physician wishes to measure the levels of the hormone estrogen in her blood. This could be done adding an antibody directed against estrogen to a sample of her blood and observing how much antigen-antibody complex formed. But, as we have learned in our studies of biochemistry, many molecules share regions of similar structure. All human steroids, for example, have a similar multi-ring structure (see Figure 3.23). A poly-clonal group of antibodies against estrogen would not be useful for this test because some of the antibodies would bind not just to estrogen, but to any steroid hormone present in the blood sample. Clearly, a clone of B cells making large amounts of an antibody that binds to only one antigenic determinant—a monoclonal antibody— would be needed. How could such a clone be produced?
A single clone of cells making a single antibody can be made by fusing a B cell (which has a finite lifetime and makes a lot of antibody) with a tumor cell (which has an infinite lifetime). The resulting hybrid cells, called hybridomas, each make a specific monoclonal antibody (Figure 18.12).
Monoclonal antibodies have many practical applications:
► Immunoassays use the great specificity of the antibodies to detect tiny amounts of molecules in tissues and fluids.
18.12 Creating Hybridomas for the Production of Monoclonal Antibodies Cancerous myeloma cells and normal B cells can be hybridized so that the proliferative properties of the myeloma cells are merged with the specificity of the antibody-producing B cells.
This technique is used, for example, to quantify the hormone made by the developing embryo for a pregnancy test.
► Immunotherapy uses monoclonal antibodies targeted against antigens on the surfaces of cancer cells. The coupling of a radioactive ligand or toxin to the antibody makes it into a medical "smart bomb." In some cases, binding of the antibody itself is enough to trigger a cellular immune response that destroys the cancer.
► Passive immunization is inoculation with an immediately acting, but not long-lasting, specific antibody. This approach is necessary when therapy must be effective quickly (within hours). Examples of such life-threatening situations include the early symptoms of rabies infection, rattlesnake bites, and babies born with hepatitis B virus infection—all cases in which the toxic nature of the infection is so serious that there is not enough time to allow the person's immune system to mount its own defense (several days at least).
A major problem with the clinical use of monoclonal antibodies is that the B cells used to produce them come from inoculated mice, so they are mouse proteins. Since mouse im-munoglobulin genes differ somewhat from the human ones, the structure of mouse immunoglobulin proteins will also be different, and so the monoclonal antibody may be antigenic to humans. To circumvent this problem, scientists can use recombinant DNA technology to make immunoglobulin genes containing constant regions from humans and variable regions from the mouse (which are not very antigenic to humans). Such a humanized antibody does not provoke an immune response in people.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.