Science and Profession (Magill’s Medical Guide, Sixth Edition)
The field of immunology deals with the ability of the immune system to react against an enormous repertoire of stimulation by antigens. In most instances, these antigens are foreign infectious agents such as viruses or bacteria. Inherent in this process is the ability to react against nearly any known determinant, whether natural or artificially produced. The most reactive antigenic determinants are proteins, though to a lesser degree, other substances such as carbohydrates (sugars), lipids (fats), and nucleic acids may also stimulate a response.
In general, the body exhibits tolerance during the constant exposure to its own tissue. The precise reasons behind tolerance are vague, but the basis for the lack of response lies in two major mechanisms: the elimination during development of immunological cells capable of responding to the body’s own tissue and the active prevention of existing reactive cells from responding to self-antigens. When this regulation fails, autoimmune disease may result.
There are two major types of immunological defense: humoral immunity and cell-mediated immunity. Humoral immunity refers to the soluble substances in blood serum, primarily antibody and complement, while cellular immunity refers to the portion of the immune response that is directly mediated by cells. Though these processes are sometimes categorized separately, they do in fact interact with and regulate each other....
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Diagnostic and Treatment Techniques (Magill’s Medical Guide, Sixth Edition)
The regulation of self-reactive lymphocytes is necessary for the maintenance of tolerance by the immune system. When regulation breaks down or is otherwise defective, either humoral or cellular immunity is generated against the cells or tissues. The resultant pathology may be simply a painful nuisance or may have potentially fatal consequences. The difference relates to the extent of damage to particular organs, in the case of organ-specific autoimmune reactions, or to the level of tissue damage in systemic disease.
Despite differences in pathology, the mechanisms of tissue damage are similar in most autoimmune diseases. Most involve the formation of immune complexes. Either antibodies bind to cell surfaces or immune complexes form in the circulation. In either case, the result is complement activation. Components of the complement pathway, in turn, can either directly damage cell membranes or trigger the infiltration of a variety of cytotoxic cells.
Because the damage associated with most autoimmune diseases results from parallel processes, methods of treatment vary little in theory from one illness to another. Most involve the treatment of resultant symptoms; for example, the use of aspirin to reduce minor inflammation and, when necessary, the use of steroids to reduce the level of the immune response. Recently, the focus has shifted from treating symptoms only to attacking the underlying disease...
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Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
During the 1950’s, F. Macfarlane Burnet published his theory of clonal selection. Burnet believed that antibody specificity was predetermined in the B cell as it underwent development and maturation. Selection of the cell by the appropriate antigen resulted in proliferation of that specific cell, a process of clonal selection.
Burnet also had to account for tolerance, however— the inability of immune cells to respond against their own antigens. Burnet theorized that during prenatal development, exposure to self-antigens, or determinants, resulted in the abortion of any self-reactive cells. Only those self-reactive immune cells that were directed against sequestered antigens survived.
Though Burnet’s theories have reached the level of dogma in the field of immunology, they fail to account for certain autoimmune disorders. In the “correct” circumstances, the body does react against itself. Though they were not recognized at the time as such, autoimmune disorders were recognized as early as 1866. In that year, W. W. Gull demonstrated the link between chilling and a syndrome called paroxysmal hemoglobinuria. When external tissue such as skin is exposed to cold, large amounts of hemoglobin are discharged into the urine. In 1904, Karl Landsteiner established the autoimmune basis for the disease by demonstrating the role of complement in the lysis of red blood cells, causing the release of hemoglobin and...
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
Delves, Peter J., et al. Roitt’s Essential Immunology. 11th ed. Malden, Mass.: Blackwell, 2006. Several chapters deal specifically with immune disorders. Concise, with a large number of illustrations, but does require a basic knowledge of biology.
Fettner, Ann Giudici. Viruses: Agents of Change. New York: McGraw-Hill, 1990. Though argumentative in her approach, Fettner provides a simple discussion of the role of viruses in disease. Included are sections on autoimmunity and the possible roles played by viruses.
Frank, Steven A. Immunology and Evolution of Infectious Disease. Princeton, N.J.: Princeton University Press, 2002. Blends research from molecular biology, immunology, pathogen biology, and population dynamics to discuss how and why parasites vary to escape recognition by the immune system, vaccine design, and the control of epidemics.
Janeway, Charles A., Jr., et al. Immunobiology: The Immune System in Health and Disease. 6th ed. New York: Garland Science, 2005. An excellent text that provides a lucid and comprehensive examination of the immune system, covering such topics as immunobiology and innate immunity, the recognition of antigen, the development of mature lymphocyte receptor repertoires, the adaptive immune response, and the evolution of the immune system.
Kindt, Thomas J., Richard A. Goldsby, and Barbara A. Osborne. Kuby Immunology....
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Immunology (World of Microbiology and Immunology)
Immunology is the study of how the body responds to foreign substances and fights off infection and other disease. Immunologists study the molecules, cells, and organs of the human body that participate in this response.
The beginnings of our understanding of immunity date to 1798, when the English physician Edward Jenner (1749823) published a report that people could be protected from deadly smallpox by sticking them with a needle dipped in the material from a cowpox boil. The French biologist and chemist Louis Pasteur (1822895) theorized that such immunization protects people against disease by exposing them to a version of a microbe that is harmless but is enough like the disease-causing organism, or pathogen, that the immune system learns to fight it. Modern vaccines against diseases such as measles, polio, and chicken pox are based on this principle.
In the late nineteenth century, a scientific debate was waged between the German physician Paul Ehrlich (1854915) and the Russian zoologist ie Metchnikoff (1845916). Ehrlich and his followers believed that proteins in the blood, called antibodies, eliminated pathogens by sticking to them; this phenomenon became known as humoral immunity. Metchnikoff and his students, on the other hand, noted that certain white blood cells could engulf and digest foreign materials: this cellular immunity, they claimed, was the real way the body fought infection.
Modern immunologists have shown that both the humoral and cellular responses play a role in fighting disease. They have also identified many of the actors and processes that form the immune response.
The immune response recognizes and responds to pathogens via a network of cells that communicate with each other about what they have "seen" and whether it "belongs." These cells patrol throughout the body for infection, carried by both the blood stream and the lymph ducts, a series of vessels carrying a clear fluid rich in immune cells.
The antigen presenting cells are the first line of the body's defense, the scouts of the immune army. They engulf foreign material or microorganisms and digest them, displaying bits and pieces of the invadersalled antigensor other immune cells to identify. These other immune cells, called T lymphocytes, can then begin the immune response that attacks the pathogen.
The body's other cells can also present antigens, although in a slightly different way. Cells always display antigens from their everyday proteins on their surface. When a cell is infected with a virus, or when it becomes cancerous, it will often make unusual proteins whose antigens can then be identified by any of a variety of cytotoxic T lymphocytes. These "killer cells" then destroy the infected or cancerous cell to protect the rest of the body. Other T lymphocytes generate chemical or other signals that encourage multiplication of other infection-fighting cells. Various types of T lymphocytes are a central part of the cellular immune response; they are also involved in the humoral response, encouraging B lymphocytes to turn into antibody-producing plasma cells.
The body cannot know in advance what a pathogen will look like and how to fight it, so it creates millions and millions of different lymphocytes that recognize random antigens. When, by chance, a B or T lymphocyte recognizes an antigen being displayed by an antigen presenting cell, the lymphocyte divides and produces many offspring that can also identify and attack this antigen. The way the immune system expands cells that by chance can attack an invading microbe is called clonal selection.
Some researchers believe that while some B and T lymphocytes recognize a pathogen and begin to mature and fight an infection, others stick around in the bloodstream for months or even years in a primed condition. Such memory cells may be the basis for the immunity noted by the ancient Chinese and by Thucydides. Other immunologists believe instead that trace amounts of a pathogen persist in the body, and their continued presence keeps the immune response strong over time.
Substances foreign to the body, such as disease-causing bacteria, viruses, and other infectious agents (known as antigens), are recognized by the body's immune system as invaders. The body's natural defenses against these infectious agents are antibodiesroteins that seek out the antigens and help destroy them. Antibodies have two very useful characteristics. First, they are extremely specific; that is, each antibody binds to and attacks one particular antigen. Second, some antibodies, once activated by the occurrence of a disease, continue to confer resistance against that disease; classic examples are the antibodies to the childhood diseases chickenpox and measles.
The second characteristic of antibodies makes it possible to develop vaccines. A vaccine is a preparation of killed or weakened bacteria or viruses that, when introduced into the body, stimulates the production of antibodies against the antigens it contains.
It is the first trait of antibodies, their specificity, that makes monoclonal antibody technology so valuable. Not only can antibodies be used therapeutically, to protect against disease; they can also help to diagnose a wide variety of illnesses, and can detect the presence of drugs, viral and bacterial products, and other unusual or abnormal substances in the blood.
Given such a diversity of uses for these disease-fighting substances, their production in pure quantities has long been the focus of scientific investigation. The conventional method was to inject a laboratory animal with an antigen and then, after antibodies had been formed, collect those antibodies from the blood serum (antibody-containing blood serum is called antiserum). There are two problems with this method: It yields antiserum that contains undesired substances, and it provides a very small amount of usable antibody.
Monoclonal antibody technology allows the production of large amounts of pure antibodies in the following way. Cells that produce antibodies naturally are obtained along with a class of cells that can grow continually in cell culture. The hybrid resulting from combining cells with the characteristic of "immortality" and those with the ability to produce the desired substance, creates, in effect, a factory to produce antibodies that work around the clock.
A myeloma is a tumor of the bone marrow that can be adapted to grow permanently in cell culture. Fusing myeloma cells with antibody-producing mammalian spleen cells, results in hybrid cells, or hybridomas, producing large amounts of monoclonal antibodies. This product of cell fusion combined the desired qualities of the two different types of cells, the ability to grow continually, and the ability to produce large amounts of pure antibody. Because selected hybrid cells produce only one specific antibody, they are more pure than the polyclonal antibodies produced by conventional techniques. They are potentially more effective than conventional drugs in fighting disease, because drugs attack not only the foreign substance but also the body's own cells as well, sometimes producing undesirable side effects such as nausea and allergic reactions. Monoclonal antibodies attack the target molecule and only the target molecule, with no or greatly diminished side effects.
While researchers have made great gains in understanding immunity, many big questions remain. Future research will need to identify how the immune response is coordinated. Other researchers are studying the immune systems of nonmammals, trying to learn how our immune response evolved. Insects, for instance, lack antibodies, and are protected only by cellular immunity and chemical defenses not known to be present in higher organisms.
Immunologists do not yet know the details behind allergy, where antigens like those from pollen, poison ivy, or certain kinds of food make the body start an uncomfortable, unnecessary, and occasionally life-threatening immune response. Likewise, no one knows exactly why the immune system can suddenly attack the body's tissuess in autoimmune diseases like rheumatoid arthritis, juvenile diabetes, systemic lupus erythematosus, or multiple sclerosis.
The hunt continues for new vaccines, especially against parasitic organisms like the malaria microbe that trick the immune system by changing their antigens. Some researchers are seeking ways to start an immune response that prevents or kills cancers. A big goal of immunologists is the search for a vaccine for HIV, the virus that causes AIDS. HIV knocks out the immune systemausing immunodeficiencyy infecting crucial T lymphocytes. Some immunologists have suggested that the chiefly humoral response raised by conventional vaccines may be unable to stop HIV from getting to lymphocytes, and that a new kind of vaccine that encourages a cellular response may be more effective.
Researchers have shown that transplant rejection is just another kind of immune response, with the immune system attacking antigens in the transplanted organ that are different from its own. Drugs that suppress the immune system are now used to prevent rejection, but they also make the patient vulnerable to infection. Immunologists are using their increased understanding of the immune system to develop more subtle ways of deceiving the immune system into accepting transplants.
See also AIDS, recent advances in research and treatment; Antibody, monoclonal; Biochemical analysis techniques; BSE, scrapie and CJD: recent advances in research; History of immunology; Immunochemistry; Immunodeficiency disease syndromes; Immunodeficiency diseases; Immunodeficiency; Immunogenetics; Immunological analysis techniques; Immunology, nutritional aspects; Immunosuppressant drugs; Infection and resistance; Laboratory techniques in immunology; Reproductive immunology; Transplantation genetics and immunology