What is serology? |

Science and Profession

The term serology comes from the Latin sero (serum, a blood liquid) and ology (the study of). Many serologic testing procedures have been developed to determine the amounts of specific antibodies the individual has circulating in his or her bloodstream. These tests can help the physician diagnose disease conditions and develop appropriate treatment regimens. To understand serological testing in relation to blood typing and immunity—two major uses of serology—it is necessary to understand the structure and nature of blood cells and the workings of the human immune system.

The surface of red blood cells contains antigenic determinants that define the individual’s blood group. There are more than twenty blood grouping systems; the most common, the ABO system, identifies individuals as being in A, B, AB, or O groups, depending on the antigenic determinant present on their red blood cells. The red blood cells of people in the A group are covered with A antigen, in the B group with B antigen, and in the AB group with both antigens. Red blood cells in the O group have neither A nor B antigens. The antigenic determinant causes the body to produce antibodies against other blood types. For example, if an individual’s red blood cells are coated with A antigen, the body will produce antibodies against B antigen. Therefore, if a person with A blood is given B blood cells, these cells will be regarded as foreign, and the body’s anti-B antibodies will dissolve them, leading to a severe, life-threatening hemolytic reaction.

All the blood groups in the ABO system are also classified as either negative or positive for Rh factor, another antigen found on the red blood cells, and so named because a similar antigen was first found in rhesus monkeys. About 85 percent of the population is Rh positive; that is, these individuals have Rh antigens on their red blood cells. If an Rh-negative person is given Rh-positive blood, he or she may tolerate the first transfusion, but a severe, even fatal, reaction can occur if a second is given. Furthermore, if an Rh-negative woman becomes pregnant with an Rh-positive baby, she may be exposed to Rh-positive red blood cells and may develop anti-Rh antibodies. This reaction may be of no significance for the first baby, but if a subsequent baby is also Rh-positive, the mother’s antibodies will attack and dissolve the red blood cells of the fetus and may cause intrauterine anemia, heart failure, or miscarriage.

As on the red blood cells, there are antigenic determinants on the surfaces of invading microorganisms that trigger the body’s immune process: When a virus, bacterium, or other infective agent enters the body, the immune system recognizes the invader as foreign. Once the organism is recognized as an enemy, the body begins to respond with the host-defense mechanism, an intricate process that not only destroys the offending pathogen but also protects against future infection by it.

Two factors determine whether an organism is antigenic and thus will trigger the immune response. First, there must be antigenic determinants present on the organism’s surface that the body identifies as foreign, or nonself. Second, the organism must be large enough to carry antigenic determinants on its surface. Antigenic determinants are large molecules; the more there are on the organism’s surface, the greater the antigenicity.

Antigens induce the production of certain white blood cells called lymphocytes. There are two basic types of lymphocytes involved in the immune process. One is the T cell, which originates in the bone marrow and travels to the thymus gland, where it becomes specialized for its immune function. The other lymphocyte is the B cell, which originates in the bone marrow and develops fully in the lymph system. T cells and B cells each develop into cells specialized for specific tasks in the immune process.

About 70 percent of T cells become helper-inducer cells, which have various functions. They promote the production of B cells, support B-cell activity, and increase the production of macrophages (cells that destroy foreign substances and dead cells). They also become “memory cells” capable of recognizing a pathogen to which the body has been exposed. If the particular pathogen reenters the body, the memory cells trigger the immune system to synthesize antibodies against it. T cells also become “killer” T cells that attack pathogens directly.

B cells produce the antibodies that are detected in seropositive blood tests. Antibodies, also called immunoglobulins, are rings, chains, or Y-shaped proteins that are carried in blood plasma. There are five groups of immunoglobulins involved in the immune system: IgG, IgA, IgM, IgD, and IgE. IgG makes up about 80 percent of all immunoglobulins and is found in tissue fluid and plasma. Its major function is to combat bacteria and viruses and to neutralize poisonous substances. IgA (13 percent) is found in the secretions of seromucous glands in the nose, gastrointestinal tract, eyes, and lungs. It also combats bacteria and viruses. IgM (6 percent) is found in blood plasma. It reacts with antigens during the first exposure to the disease organism. IgD (less than 1 percent) is found on the surface of most B cells. Its activities are not fully understood, but it is thought to be involved in the production of antibodies. IgE (less than 1 percent) is bound to mast cells found in connective tissue. It promotes allergic reactions.

Antibodies work in two ways—by direct attack on an antigen and by activating a protein complex called a complement. In direct attack, there are four ways in which antibodies destroy antigens: agglutination, which causes antigens to clump together; precipitation, which causes antigens to form insoluble substances; neutralization, which prevents antigens from producing toxic substances; and lysis, which causes the cell walls of antigens to rupture.

The activation of a complement causes three main activities: chemotaxis, which attracts macrophages and other white blood cells to the area, where they can eliminate the pathogens that are present; opsonization, which alters the structure of the antigen cell wall, making it easier for macrophages to engulf and destroy it; and inflammation, a process that helps to prevent the spread of pathogens.

Like T cells, some B cells become memory cells that help prevent reinfection by recognizing and destroying a pathogen that they have previously encountered.

Diagnostic and Treatment Techniques

The major use for seronegative-seropositive testing is in blood typing. The patient’s blood type is recorded as part of his or her medical history and is required for a blood transfusion to ensure that the patient receives blood from a compatible donor. Blood typing is an activity conducted in, or readily available to, virtually every medical facility. A major example is the Coomb’s test, which detects antibodies on red blood cells in the bloodstream and establishes whether the patient has sensitized cells. This information is helpful in cross-matching donor and patient blood and in the diagnosis of hemolytic anemia.

Another important aspect of serologic testing is to determine the immune status of an individual—that is, whether a person or a local population is immune to a specific disease or is susceptible and therefore should be vaccinated. Such tests are geared to the identification of antibodies that protect against certain diseases. These antibodies are created by exposure to the disease-causing microorganism as a result of infection by the organism itself; vaccination, in which a modified form of the microorganism is used to trigger the body’s immune response; or immunity that is acquired by a newborn baby from a mother, an immune state that lasts only a few months. A test that comes back seronegative or with very low antibody levels indicates that the patient is not immune to a given disease. A test that comes back seropositive indicates that the patient has circulating antibodies characteristic of a specific disease and that, if the amount of antibodies is high enough, the patient is immune to the disease.

A good example of immune status determination is the testing for hepatitis B surface antigen among health care workers. Hepatitis B is a blood-borne disease that can be transmitted when infected blood or other body fluids enter the bloodstream of another person. Transmission often occurs among health care workers because they are often exposed to the blood and body fluids of patients during operating procedures, dental procedures, or even when the nurse or other health care worker draws blood and is inadvertently stuck with the needle. Tests show that health care workers are seropositive for hepatitis B surface antigen at rates far above the general population. For example, 25 percent of surgeons and dentists become seropositive after five to ten years in practice. These tests prove that some health care workers are at high risk for contracting hepatitis B from their patients. Therefore, routine vaccination is recommended for those health care workers who are likely to be exposed to the blood and body fluids of patients carrying the hepatitis B virus.

Seronegative-seropositive testing can also reveal whether a person who has been vaccinated against a certain disease has achieved immunity (has “seroconverted” and developed antibodies in response to the antigen), whether the individual has not achieved immunity, or whether the individual has achieved immunity and then lost it.

No vaccine is 100 percent effective, but the better ones induce an immune response in 90 to 98 percent of individuals. For example, measles vaccine is about 95 percent effective. This means that most of the children who have received it are immune to measles, but 5 percent or so remain susceptible.

A few vaccines produce lifelong immunity. With most, however, the amount of antibody diminishes after time, and the vaccination must be repeated to maintain immunity. In other words, the patient is given a “booster” shot. In the late 1980s, many children who had received measles vaccine and who had seroconverted were found to be seronegative: They had lost their immunity to measles. This finding suggested that the measles vaccine conveyed an immunity that could diminish with time. Therefore, medical authorities and public health organizations revised their recommendations for mass vaccination against measles. Instead of only one vaccination of the infant at twelve to fifteen months of age, the protocol now recommends repeating the vaccination at a later date.

Serologic tests are used in virtually all branches of medicine. One group of seronegative-seropositive tests is used to detect fetal abnormalities. Another group, autoantibody tests, detects such diseases as autoimmune hepatitis, thyroiditis, and systemic
lupus erythematosus (SLE). One example is testing for rheumatoid factor, an antibody that appears in the blood of adult patients with rheumatoid arthritis. Its presence will help the physician make a diagnosis and determine a course of treatment for a patient with joint inflammation. Similarly, specific antibodies will indicate specific disease conditions. A patient with lupus has antinuclear antibody (ANA). Rheumatic fever diagnosis requires evidence of the bacteria Streptococcus pyogenes. Syphilis patients have antibodies to the spirochete Treponema pallidum. Patients with
mononucleosis are seropositive for heterophile antibodies.

Viral, bacterial, and fungal tests detect antibodies or antigens developed in response to infection. These include the antistreptolysin-O test for streptococcal antibodies, the febrile agglutination test to detect diseases caused by salmonella, and the latex particle agglutination (LPA) tests for antigens of other bacteria. Also in this group are the hepatitis-B surface and core antigen tests, which are used to screen blood donors as well as to identify persons who have been exposed to hepatitis B. Fungal serology tests are used to detect various fungal infections. The fluorescent treponemal antibody absorption test is used to diagnose syphilis.

Serologic tests called general humoral tests are used to detect and diagnose various bodily dysfunctions. Another group called the general cellular tests includes the lymphocyte transformation test to determine whether transplant donors and recipients are compatible. In this group, the terminal deoxynucleotidyl transferase test is used to diagnose leukemias and lymphomas, as well as to monitor the progress of treatment. In cancer therapy, the carcinoembryonic antigen test (CEA) is used to gauge the response of certain cancers to treatment or to detect the recurrence of certain cancers.

A major new field for serology is emerging with monoclonal antibody research. In this science, antibodies can be manufactured in the laboratory. Instead of injecting a patient with modified antigen and inducing the body to create antibodies to it (as in vaccination), physicians can provide the patient with the antibodies themselves. Because these antibodies are absolutely identical to their parent protein or cell and to one another, they are not subject to the variables present in antibodies produced by other methods. They have properties that make them ideal for treating certain diseases.

Once the analysis of tissue identifies a specific antigen, it may be possible to program monoclonal antibodies to search out and destroy them. It is also possible to link the antibodies to chemotherapeutic agents. Thus, monoclonal antibodies can not only target specific antigens but also bring medication to the specific tissues where it is required. In cancer therapy, these qualities promise to improve the efficiency of treatment greatly. With monoclonal antibodies, cancer-destroying drugs can be brought directly to the cancer cell and can destroy it without harming other body tissues, thus reducing the severity of side effects from chemotherapy.

Perspective and Prospects

The science of serology and serological testing for antibodies and antigens in the body have become mainstays of modern medical diagnosis and treatment for a wide range of diseases. Virtually every individual in the industrialized world and most members of the developing world urban populations undergo serologic testing as part of their regular medical routine.

Serological testing is part of every hospital workup, almost every routine medical examination, every blood transfusion, all transplant procedures, many diagnostic procedures, and many treatment regimens. It is the basis for most epidemiological studies that enumerate the extent of susceptibility to individual diseases in various populations and hence directs the development of immunization programs. It is an integral part of vaccine production and is critical in the development of new vaccines. With the development of monoclonal antibody research, serology enters a new era where the possibilities of improved serologic testing and therapeutic modalities seem almost unlimited.

Serological testing and therapy, so far, have been based on the manipulation and modification of living organisms. It is theoretically possible to develop vaccines and therapeutic agents that are completely synthetic in structure. This science promises greater specificity and efficacy, both for vaccines and for disease treatment.

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