Structure and Functions (Magill’s Medical Guide, Sixth Edition)
The immune system is capable of recognizing and identifying many different substances foreign to the human body. To function properly, this system must receive, interpret, and transmit large amounts of information about invaders from outside or within the body. These constant and ever-changing threats to the body must be met and destroyed by one complex system—namely, the human immune system. Many organs and parts of the body play a major role in maintaining resistance; some have more important roles than others, but all parts must work in unison. The circulatory and lymphatic systems, along with specific organs, are of primary importance in the overall workings of the immune system.
Blood. Besides the outer protective layer of the skin and mucous membranes, the first line of defense in the immune system includes the blood in the circulatory system. About 50 percent of human blood is made up of a fluid called plasma, which contains water, proteins, carbohydrates, vitamins, hormones, and cellular waste. The other half of blood is composed of white cells, red cells, and platelets. The red blood cells, called erythrocytes, are responsible for moving oxygen from the lungs to the other parts of the body. The special platelet cells, called thrombocytes, enable the blood to form clots, thus preventing severe bleeding. An unborn child produces red and white blood cells in the spleen and liver, while a newborn makes...
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The Responses of the Immune System (Magill’s Medical Guide, Sixth Edition)
Failures of the immune system can lead to devastating diseases, either because the immune system attacks itself or because it fails to defend against outside foreign antigen matter. An antigen can be any substance that stimulates the body to fight, ranging from a bacterial infection to the virus that causes acquired immunodeficiency syndrome (AIDS).
When the body fights against an antigen, the immune system can produce two types of response, either a cellular immune response or a humoral immune response. The cellular response involves specific types of cells that recognize, attack, and destroy the invading pathogen or antigen. It is the primary response against most viruses, many fungi, parasitic organisms and some bacteria (for example, mycobacteria), and against transplanted tissues. The humoral immune response, which consists of complement and antibodies, is the body’s main defense against most other bacteria. The two systems work together, however, communicating by complex chemical mediators.
Another way of looking at how the body fights to keep itself healthy is to separate the immune responses into either primary or secondary responses. The second time that a given antigen enters the body, the immune system attacks with what is called the secondary immune response stored in special immune memories, making it faster and more extensive than the primary response that occurred when the antigen...
(The entire section is 862 words.)
Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
In the same way that the discovery of penicillin shocked the world, immunology has created endless possibilities in medicine. When surgeons found that they could transplant an organ from one person to another, the interest in immunology exploded.
This field of medicine has discovered that the immune system’s power and effectiveness can be lessened because of several factors. Improper diet, stress, disease, and excessive physical activity levels can depress the immune system. Other factors that can modify immunity include age, genetics, and metabolic and environmental factors. The anatomical, physiological, and microbial factors are shown in the susceptibility of the young and the very old to infections. For the young, the system is immature, while the aged have suffered a lifetime of assaults from pathogens. The impact of psychological stress is difficult to measure, yet it holds the potential for negatively affecting the immune system.
Before immunology can be fully understood, more knowledge must be gained about how antibodies are made and how they develop memories. Lymphocytes must be examined to discover what role they play in the immune response. Studies must look at not only the whole picture of the immune system but also its smaller parts—the organs and how each participates. Such studies could lead to better success in transplanting these organs. Unanswered questions remain about how the immune...
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
Adelman, Daniel C., et al., eds. Manual of Allergy and Immunology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2002. Examines research developments and the clinical diagnosis and treatment of allergies and immune disorders. Topics include asthma, disorders of the eye, diseases of the lung, anaphylaxism, insect allergies, drug allergies, rheumatic diseases, transplantation immunology, and immunization.
Delves, Peter J., et al. Roitt’s Essential Immunology. 11th ed. Malden, Mass.: Blackwell, 2006. Provides a fine description of immunology.
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.
Immune Web. http://www.immuneweb.org. A mailing list and resource center for people with chronic fatigue syndrome, multiple chemical sensitivities, lupus, allergies, environmental illness, fibromyalgia, candida, and other immune system disorders.
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...
(The entire section is 392 words.)
Immune system (Forensic Science)
The organization of the immune system can be described in various ways based on the physical and functional characteristics of the system’s components. For example, the immune system can be divided into humoral (soluble molecules such as antibodies and complement) and cellular immune systems (white blood cells, or leukocytes). Another way to describe the immune system is to distinguish between the adaptive (or acquired) immune system and the innate (or natural) immune system.
The adaptive immune system exhibits a lag phase before response and great specificity for particular foreign materials; it has a “memory” for foreign materials and responds more quickly and strongly upon subsequent encounters. Prominent components of the adaptive immune system are white blood cells called T and B lymphocytes and molecules such as antibodies and T-cell antigen receptors. The natural immune system’s response is immediate, does not alter in magnitude when reencountering foreign material, and operates against broad classes of materials. Prominent components of the innate immune system include molecules of the complement system and cells such as monocyte/macrophages, neutrophils, natural killer cells, eosinophils, mast cells, and basophils.
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Cells and Functions (Forensic Science)
The cells of the immune system include different types of white blood cells that are also known as leukocytes. They all originate from the bone marrow and are found in tissues throughout the body as well as in specialized immune tissues such as lymph nodes and vessels, spleen, appendix, and tonsils. The cells have shared and unique functions such as engulfment of foreign particles (phagocytosis), release of microbe-killing molecules, and secretion of molecules called cytokines that affect leukocytes and other cells.
Cells such as B and T lymphocytes are capable of undergoing clonal expansion. That is, these lymphocytes consist of populations of distinct cells, each bearing a particular surface receptor capable of binding a particular foreign substance—an antigen. Upon binding a particular foreign substance, such a lymphocyte can divide to produce copies of itself (clones) that can produce more of the corresponding receptor for the foreign substance. In order to manipulate the immune system in the test tube or the body to produce substances useful in forensic testing, scientists employ detailed knowledge of the properties of immune system cells.
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Antigens and Antibodies (Forensic Science)
Antigens are substances that provoke immune system responses, such as the generation of cells or antibodies that can specifically bind the antigens. Forensic scientists frequently encounter a number of antigens in their work, including hemoglobin, prostate-specific antigen (PSA), alpha amylase, and semenogelin. Other forensically significant antigens are carbohydrate substances such as ABO blood group antigens and Lewis antigens. Also of interest to forensic scientists are small parts of antigens known as haptens, which include drugs of abuse such as cannabis, heroin, cocaine, and amphetamines and their metabolites.
Antibodies are a class of proteins that are synthesized and secreted only by B lymphocytes, a subpopulation of white blood cells. The five classes of antibodies (termed IgG, IgM, IgA, IgE, and IgD) all have different structural and functional characteristics.
Antibodies are Y-shaped proteins, and the basic unit is composed of four polypeptide chains, two heavy chains and two light chains. Both light and heavy chains have “variable” regions that differ in composition among antibodies and “constant” regions that are identical or similar within a particular class of antibodies. The site on antibodies that binds antigen encompasses the tips of one heavy chain and one light chain in the arms of the Y-shaped antibody and involves the variable regions. The constant regions, depending on the class,...
(The entire section is 347 words.)
Forensic Applications of Immunology (Forensic Science)
In forensic science, antibodies are used extensively in the areas of serology and toxicology. In serology, antibodies are used in tests to detect and identify human blood, semen, and saliva stains. In toxicology, antibodies are used in tests for poisons and for drugs of abuse. (Like the drug tests performed by forensic scientists during criminal investigations, the tests widely used by some employers and sports leagues to screen employees and players for drugs of abuse and banned performance-enhancing substances are also antibody-based.)
Another example of the use of antibodies in forensic science is found in the area of DNA (deoxyribonucleic acid) analysis. Forensic scientists use a technique known as polymerase chain reaction (PCR) to make it possible to test minute quantities of DNA in evidence. In one version of the technique called hot-start PCR, the accuracy of the process is increased by the inclusion of an antibody to the DNA polymerase used.
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Further Reading (Forensic Science)
Gaensslen, R. E. Sourcebook in Forensic Serology, Immunology, and Biochemistry. Washington, D.C.: National Institute of Justice, 1983. Comprehensive text covers all aspects of forensic serology.
Houck, Max M., and Jay A. Siegel. Fundamentals of Forensic Science. Burlington, Mass.: Elsevier Academic Press, 2006. Good source of information on the basics of biological fluids and techniques of serological analysis.
James, Stuart H., and Jon J. Nordby, eds. Forensic Science: An Introduction to Scientific and Investigative Techniques. 2d ed. Boca Raton, Fla.: CRC Press, 2005. Introductory-level text provides illustrated explanations of forensic serology methods.
Kindt, Thomas J., Richard A. Goldsby, and Barbara A. Osborne. Kuby Immunology. 6th ed. New York : W. H. Freeman, 2007. Well-written text includes coverage of the scientific principles applied in forensic serology.
O’Gorman, Maurice R. G., and Albert D. Donnenberg, eds. Handbook of Human Immunology. 2d ed. Boca Raton, Fla.: CRC Press, 2008. Review of immunological basics includes discussion of techniques used in forensic serology.
Saferstein, Richard. Criminalistics: An Introduction to Forensic Science. 9th ed. Upper Saddle River, N.J.: Pearson Prentice Hall, 2007. Textbook discusses all subdisciplines within forensic science. Chapter 12 provides a general overview and history of forensic...
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Immune System (Encyclopedia of Science)
The immune system in a vertebrate (an organism with a backbone) consists of all the cells and tissues that recognize and defend the body against foreign chemicals and organisms. For example, suppose that you receive a cut in your skin. Microorganisms living on your skin are then able to enter your body. They pass into the bloodstream and pass throughout your body. Some of these microorganisms are pathogenic, that is, they may cause illness and even death. As soon as those microorganisms enter your body, its immune system begins to identify them as foreign to your body and to produce defenses that will protect your body against any diseases they may cause.
The study of the immune system is known as immunology and scientists engaged in this field of research are immunologists. Our understanding of the way in which the immune system functions in animals has made possible the prevention of various diseases by means of immunizations. The term immunization refers to the protection of an individual animal against a disease by the introduction of killed or weakened disease-causing organisms into its bloodstream.
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Immune System (Encyclopedia of Nursing & Allied Health)
The immune system is composed of cells, organs, tissues, and molecules that protect the body from disease. The term "immunity" comes from the Latin word immunitas.
Anatomic barriers provide protection against invading bacterial and viral pathogens. The skin is composed primarily of keratin, which cannot be digested by most microorganisms. The skin is usually dry with a high salt concentration due to sweat. These conditions are not favorable for bacterial growth. Sweat and sebaceous skin secretions also contain substances that kill bacteria. Some types of bacteria inhabit the skin surface and do not cause disease under normal conditions (microflora). These bacteria may produce substances that kill other more pathogenic bacteria. The microflora may also consume nutrients required by pathogens. This gives rise to a competitive relationship that limits the growth of the pathogens. If the skin is broken, due to injuries or burns, harmful bacteria may enter and give rise to infection. The cilia of the lungs protect this organ from inhaled pathogens, transporting secretions to the throat so that they can be swallowed and destroyed by stomach acid. Secretions in the nose, saliva, and components of tears also contain substances that protect against bacteria and viruses.
Cells of the immune system
LYMPHOCYTES. There are two major types of lymphocytes, the T-cells and B-cells, which comprise 200% of the white blood cells in normal adult human circulation. T-cells mature and differentiate in the thymus gland and assist in cellular immune responses. These cells are responsible for the recognition of antigens (materials that give rise to an immune response, such as components of pathogenic bacteria). There are three major types of T-cells that are classified according to their function: cytotoxic T cells (Tc) that kill abnormal cells, helper T cells (Th) that enhance an immune response, and suppressor T-cells (Ts) that diminish the immune response. The B-cells mature in the bone marrow and recognize antigens with the help of T-cells. Upon activation, these cells give rise to plasma cells, which produce antibodies (immunoglobulins). Antibodies bind with toxic pathogen proteins or antigens and interact with other cells to remove the invader from the system. Plasma cells are found in the lymph nodes, spleen and bone marrow. B-cells also give rise to memory cells that remain alive for long periods of time and assist in a more effective immune response upon the next exposure to the same antigen.
The natural killer cells (NK) are a third type of lymphocyte and comprise approximately 3% of normal blood circulation. These large cells are responsible for the killing of some tumors and virus-infected cells. Additionally, some cells can be induced to kill their targets in a non-specific manner under the appropriate conditions. These cells are called lymphokine activated killer (LAK) cells.
GRANULOCYTES. The granulocytes or polymorphonuclear leukocytes (PMNs) are a group of cells that display a characteristic staining of granules in blood smears, hence their name. These cells have a short life span in the blood (about two or three days), and make up the majority of the white blood cells under normal conditions. They are usually found in greater numbers during an immune response to injury or infection. The neutrophils are a very important type of granulocyte and demonstrate phagocytosis (ingestion of particles by cells, such as particles of bacteria, with ultimate destruction by lysosomal enzymes). These cells are critical in the development of the immune response to pathogens and can migrate from the blood to the tissues during infection by a process known as chemotaxis (the movement of cells in response to and external chemical stimulation). They comprise approximately 405% of the blood. The eosinophils are mainly involved in an immune response to parasitic infection and also play a role in the allergic response, and comprise only 1% of the blood. The basophils, normally present in low numbers in the circulation (less than 1% of the blood), are thought to play a role in the inflammation and damage to tissue associated with allergic reactions.
MONOCYTES, MACROPHAGES, AND MAST CELLS. Monocytes are a type of cell that circulates in the bloodstream, comprising 20% of the blood. Upon migration into the tissues, these cells differentiate into macrophages that are capable of ingesting microorganisms by phagocytosis and have a critical role in the host defense to pathogens. They also produce substances called monokines that are a type of secreted protein (cytokine) that affects the actions of other cells.
Mast cells are distributed in the connective tissues, especially in the skin and mucosal surfaces of the respiratory, gastrointestinal, and urogenital tracts as well as the eye. These cells are also involved in the allergic response.
PLATELETS. Platelets are cell fragments in the blood that are involved in blood clotting and inflammation.
DENDRITIC CELLS. Dendritic cells are potent stimulators of immune responses. These cells play an important role in the increased immune response upon a second exposure to an antigen. Dendritic cells are distributed throughout the body, especially in the T-cell areas of lymphoid organs. In the lymphoid tissue, dendritic cells are involved in the stimulation of T-cell responses.
Central lymphoid tissues
The central lymphoid organs include the bone marrow and thymus. At these sites, the lymphocytes interact with other cells to enhance their development or increase their ability to assist in an immune response. They also acquire the ability to recognize specific antigens before they actually become exposed to them, and are antigen independent. At this stage the lymphocytes are called naïve lymphocytes because they have not yet been exposed to antigens. The bone marrow is the site of hematopoiesis. Both B-lymphocytes and T-lymphocytes come from this site, but only the B cells undergo maturation in this area (hence the name B-cell T-cell).
Peripheral lymphoid tissues
The peripheral lymphoid tissues include the lymphatic vessels, lymph nodes, various lymphoid tissues, and spleen. The events that occur in these areas require exposure to an antigen, and are called antigen-dependent events.
The filtration of the blood results in the production of extracellular fluid called lymph. The lymphatic vessels that carry the fluid back to the bloodstream also carries cells with antigens. These antigens come from other sites within the body where infection may be present. The fluid passes through the lymph nodes. This fluid is eventually returned to the blood via lymphatic vessels. All the lymph from the body is carried back to the heart by way of the thoracic duct.
Lymph nodes and lymphoid tissue
Lymph nodes are distributed along lymphatic vessel pathways and act as a filter for the lymph. The lymph nodes are distributed throughout the lymphatic system, and are especially prominent in the neck, axilla (underarm), and groin. These fibrous nodes contain immune cells such as lymphocytes, macrophages, and dendritic cells. Dendritic cells have long, filamentous cytoplasmic processes. These processes have the ability to bind antibodies such that the antibodies can also bind with their specific antigens. This creates a web that traps antigens. The macrophages in the lymph nodes degrade debris and
extract material that contains antigens, such as those from pathogenic bacteria. The structure of the lymph nodes is such that both T-and B-cells are exposed to this antigenic material. The cells that recognize this material are held in the lymphoid nodes and tissues where they multiply and differentiate. These cells become effector cells that are capable of fighting disease. The node may enlarge during this process, giving rise to the clinical observation of swollen glands.
Lymphocytes can also be found in several other areas throughout the body. The gut-associated lymphoid tissue is a broad term that describes lymphoid tissue found in the Peyer's patches of the intestine, appendix, adenoids, and tonsils. Cells that protect the respiratory tract are called bronchial-associated lymphoid tissue (BALT). Other mucosal areas are protected as well, and are collectively known as mucosal-associated lymphoid tissue (MALT).
Blood is filtered in the spleen, where damaged or dead red blood cells are removed from the blood as well as antigens. This organ also serves as a site for storage of erythrocytes and platelets. In the fetus, it is the site of erythropoiesis (formation of red blood cells). Within this organ reside B-cells, T-cells, macrophages, and dendritic cells. As in the lymph nodes, lymphocytes are trapped in this organ. Antibodies and effector cells are produced in the spleen.
Common disorders and diseases
Hypersensitivity reactions result from an immunemediated inflammatory response to an antigen that would normally be innocuous (causing no harm to the body). Examples include allergic reactions, such as hay fever, asthma, reactions to insect bites, and the systemic anaphylactic shock that occurs in response to bee stings, allergies to antibiotics, and foods.
Delayed-type hypersensitivity reactions are due to the release of lymphokines. These lymphokines are small polypetides produced by lymphocytes that have been stimulated by an antigen, affecting other cells. This hypersensitivity reaction may occur as part of the normal immune response to infection by bacteria and viruses. This effect is responsible for the tissue damage in the lungs due to tuberculosis, the skin lesions that occur in leprosy and herpes, and rashes associated with chicken pox and measles. This may also occur via skin exposure to cosmetics, poison ivy, and allergy to metals in jewelry, resulting in contact dermatitis.
Autoimmune diseases occur when the immune system begins to attack the body or "self." In Grave's disease, antibodies are produced against the thyroid-stimulating hormone (TSH) receptor. In multiple sclerosis (MS), antibodies are produced against elements of the myelin sheaths in the brain and spinal cord. The effects of myasthenia gravis are traced to antibodies directed against the acetylcholine receptor. Following a heart attack, antibodies may form against heart muscle antigens resulting in autoimmune myocarditis. Rheumatoid arthritis (RA) develops from complexes pf antibodies to immunoglobulin G (IgG) in the joints and connective tissue. In systemic lupus erythematosus, the body produces antibodies directed against nuclear antigens and DNA.
In acquired immunodeficiency syndrome (AIDS), the HIV retrovirus attacks T-cells (CD4), dendritic cells, and macrophages. The number of CD4 T-cell in the blood eventually declines and the body can no longer resist the HIV infection. With the immune system compromised, constitutional disease can develop with fever, weight loss, or diarrhea. Neurological disease can occur, resulting in dementia and effects to the peripheral nervous system. Pathogenic microorganisms may cause opportunistic infections in this compromised immune state, such as pneumonia, diarrhea, skin and mucous membrane infections, and central nervous system infections. Cancers may also arise, such as lymphomas. Death from HIV is due to one of these complications or a combination of effects.
Antibodies (immunoglobulins)roteins that bind to their corresponding specific antigen.
Antigen material that gives rise to an immune response.
Autoimmune diseasen immune response that occurs when the immune system begins to attack the body or self.
B lymphocyte lymphocyte that contains an immunoglobulin on the surface (the B-cell receptor). B cells mature in the bone marrow.
Effector cellsature lymphocytes that assist in the removal of pathogens from the system and do not require further differentiation to perform this function.
Hypersensitivityn immune reaction that results from an immune mediated inflammatory response to an antigen that would normally be innocuous.
Macrophagesells that are capable of ingesting microorganisms by phagocytosis and have a critical role in the host defense to pathogens.
Pathogen microorganism that has the potential to cause a disease.
T cytotoxic cells (Tc) lymphocytes that kill abnormal cells.
T helper cells (Th) lymphocytes that enhance an immune response.
T lymphocyte lymphocyte that matures in the thymus and has receptors related to CD3 complex proteins.
T suppressor cells (Ts) lymphocytes that diminish the immune response.
Anderson, William L. Immunology. Madison, CT: Fence Creek Publishing, 1999.
Janeway, Charles A., et al. Immunobiology: The Immune System in Health and Disease. New York: Elsevier Science London/Garland Publishing, 1999.
Roitt, Ivan, and Arthur Rabson. Really Essential Medical Immunology. Malden: Blackwell Science, 2000.
Sharon, Jacqueline. Basic Immunology. Baltimore: Williams and Wilkins, 1998.
Widmann, Frances K., and Carol A. Itatani. An Introduction to Clinical Immunology and Serology. Philadelphia: F. A. Davis Company, 1998.
Wier, Donald M., and John Stewart. Immunology. New York: Churchchill Linvingstone, Inc., 1997.
American Autoimmune Related Disease Association. <<a href="http://www.aarda.org">http://www.aarda.org>.
Mayo Clinic <<a href="http://www.mayoclinic.com">http://www.mayoclinic.com>.
Med Web, Emory University. <<a href="http://www.medweb.emory.edu/MedWeb/">http://www.medweb.emory.edu/MedWeb/>.
Jill Ilene Granger, M.S.
Immune System (World of Microbiology and Immunology)
The immune system is the body's biological defense mechanism that protects against foreign invaders. Only in the last century have the components of that system and the ways in which they work been discovered, and more remains to be clarified.
The true roots of the study of the immune system date from 1796 when an English physician, Edward Jenner, discovered a method of smallpox vaccination. He noted that dairy workers who contracted cowpox from milking infected cows were thereafter resistant to smallpox. In 1796, Jenner injected a young boy with material from a milkmaid who had an active case of cowpox. After the boy recovered from his own resulting cowpox, Jenner inoculated him with smallpox; the boy was immune. After Jenner published the results of this and other cases in 1798, the practice of Jennerian vaccination spread rapidly.
It was Louis Pasteur who established the cause of infectious diseases and the medical basis for immunization. First, Pasteur formulated his germ theory of disease, the concept that disease is caused by communicable microorganisms. In 1880, Pasteur discovered that aged cultures of fowl cholera bacteria lost their power to induce disease in chickens but still conferred immunity to the disease when injected. He went on to use attenuated (weakened) cultures of anthrax and rabies to vaccinate against those diseases. The American scientists Theobald Smith (1859934) and Daniel Salmon (1850914) showed in 1886 that bacteria killed by heat could also confer immunity.
Why vaccination imparted immunity was not yet known. In 1888, Pierre-Paul-Emile Roux (1853933) and Alexandre Yersin (1863943) showed that diphtheria bacillus produced a toxin that the body responded to by producing an antitoxin. Emil von Behring and Shibasaburo Kitasato found a similar toxin-antitoxin reaction in tetanus in 1890. Von Behring discovered that small doses of tetanus or diphtheria toxin produced immunity, and that this immunity could be transferred from animal to animal via serum. Von Behring concluded that the immunity was conferred by substances in the blood, which he called antitoxins, or antibodies. In 1894, Richard Pfeiffer (1858945) found that antibodies killed cholera bacteria (bacterioloysis). Hans Buchner (1850902) in 1893 discovered another important blood substance called complement (Buchner's term was alexin), and Jules Bordet in 1898 found that it enabled the antibodies to combine with antigens (foreign substances) and destroy or eliminate them. It became clear that each antibody acted only against a specific antigen. Karl Landsteiner was able to use this specific antigen-antibody reaction to distinguish the different blood groups.
A new element was introduced into the growing body of immune system knowledge during the 1880s by the Russian microbiologist Elie Metchnikoff. He discovered cell-based immunity: white blood cells (leucocytes), which Metchnikoff called phagocytes, ingested and destroyed foreign particles. Considerable controversy flourished between the proponents of cell-based and blood-based immunity until 1903, when Almroth Edward Wright brought them together by showing that certain blood substances were necessary for phagocytes to function as bacteria destroyers. A unifying theory of immunity was posited by Paul Ehrlich in the 1890s; his "side-chain" theory explained that antigens and antibodies combine chemically in fixed ways, like a key fits into a lock. Until this time, immune responses were seen as purely beneficial. In 1902, however, Charles Richet and Paul Portier demonstrated extreme immune reactions in test animals that had become sensitive to antigens by previous exposure. This phenomenon of hypersensitivity, called anaphylaxis, showed that immune responses could cause the body to damage itself. Hypersensitivity to antigens also explained allergies, a term coined by Pirquet in 1906.
Much more was learned about antibodies in the mid-twentieth century, including the fact that they are proteins of the gamma globulin portion of plasma and are produced by plasma cells; their molecular structure was also worked out. An important advance in immunochemistry came in 1935 when Michael Heidelberger and Edward Kendall (1886972) developed a method to detect and measure amounts of different antigens and antibodies in serum. Immunobiology also advanced. Frank Macfarlane Burnet suggested that animals did not produce antibodies to substances they had encountered very early in life; Peter Medawar proved this idea in 1953 through experiments on mouse embryos.
In 1957, Burnet put forth his clonal selection theory to explain the biology of immune responses. On meeting an antigen, an immunologically responsive cell (shown by C. S. Gowans (1923) in the 1960s to be a lymphocyte) responds by multiplying and producing an identical set of plasma cells, which in turn manufacture the specific antibody for that antigen. Further cellular research has shown that there are two types of lymphocytes (nondescript lymph cells): B-lymphocytes, which secrete antibody, and T-lymphocytes, which regulate the B-lymphocytes and also either kill foreign substances directly (killer T cells) or stimulate macrophages to do so (helper T cells). Lymphocytes recognize antigens by characteristics on the surface of the antigen-carrying molecules. Researchers in the 1980s uncovered many more intricate biological and chemical details of the immune system components and the ways in which they interact.
Knowledge about the immune system's role in rejection of transplanted tissue became extremely important as organ transplantation became surgically feasible. Peter Medawar's work in the 1940s showed that such rejection was an immune reaction to antigens on the foreign tissue. Donald Calne (1936) showed in 1960 that immunosuppressive drugs, drugs that suppress immune responses, reduced transplant rejection, and these drugs were first used on human patients in 1962. In the 1940s, George Snell (1903996) discovered in mice a group of tissue-compatibility genes, the MHC, that played an important role in controlling acceptance or resistance to tissue grafts. Jean Dausset found human MHC, a set of antigens to human leucocytes (white blood cells), called HLA. Matching of HLA in donor and recipient tissue is an important technique to predict compatibility in transplants. Baruj Benacerraf in 1969 showed that an animal's ability to respond to an antigen was controlled by genes in the MHC complex.
Exciting new discoveries in the study of the immune system are on the horizon. Researchers are investigating the relation of HLA to disease; certain types of HLA molecules may predispose people to particular diseases. This promises to lead to more effective treatments and, in the long run, possible prevention. Autoimmune reaction, in which the body has an immune response to its own substances, may also be a cause of a number of diseases, like multiple sclerosis, and research proceeds on that front. Approaches to cancer treatment also involve the immune system. Some researchers, including Burnet, speculate that a failure of the immune system may be implicated in cancer. In the late 1960s, Ion Gresser (1928) discovered that the protein interferon acts against cancerous tumors. After the development of genetically engineered interferon in the mid-1980s finally made the substance available in practical amounts, research into its use against cancer accelerated. The invention of monoclonal antibodies in the mid-1970s was a major breakthrough. Increasingly sophisticated knowledge about the workings of the immune system holds out the hope of finding an effective method to combat one of the most serious immune system disorders, AIDS.
Avenues of research to treat AIDS includes a focus on supporting and strengthening the immune system. (However, much research has to be done in this area to determine whether strengthening the immune system is beneficial or whether it may cause an increase in the number of infected cells.) One area of interest is cytokines, proteins produced by the body that help the immune system cells communicate with each other and activate them to fight infection. Some individuals infected with the AIDS virus HIV (human immunodeficiency virus) have higher levels of certain cytokines and lower levels of others. A possible approach to controlling infection would be to boost deficient levels of cytokines while depressing levels of cytokines that may be too abundant. Other research has found that HIV may also turn the immune system against itself by producing antibodies against its own cells.
Advances in immunological research indicate that the immune system may be made of more than 100 million highly specialized cells designed to combat specific antigens. While the task of identifying these cells and their functions may be daunting, headway is being made. By identifying these specific cells, researchers may be able to further advance another promising area of immunologic research, the use of recombinant DNA technology, in which specific proteins can be mass-produced. This approach has led to new cancer treatments that can stimulate the immune system by using synthetic versions of proteins released by interferons.
See also Antibody and antigen; Antibody formation and kinetics; Antibody, monoclonal; Antibody-antigen, biochemical and molecular reactions; B cells or B lymphocytes; Bacteria and bacterial infection; Germ theory of disease; Immunity, active, passive and delayed; Immunity, cell mediated; Immunity, humoral regulation; Immunochemistry; Immunodeficiency; Immunogenetics; Immunologic therapies; Immunological analysis techniques; Immunology, nutritional aspects; Immunology; Immunosuppressant drugs; Infection and resistance; Invasiveness and intracellular infection; Major histocompatibility complex (MHC); T cells or T-lymphocytes; Transmission of pathogens; Transplantation genetics and immunology; Viruses and responses to viral infection
Immune System (World of Forensic Science)
A staple in forensic investigations is the use of antibodies to detect a target antigen. Blood typing and the detection of bacteria, or their elaborated toxins, rely on the recognition of antigens by their corresponding antibodies. The production of antibodies is one aspect of the immune system, the body's biological defense mechanism that protects against foreign invaders.
The true roots of the study of the immune system date from 1796, when English physician Edward Jenner discovered a method of smallpox vaccination. He noted that dairy workers who contracted cowpox from milking infected cows were thereafter resistant to smallpox. In 1796, Jenner injected a young boy with material from a milkmaid who had an active case of cowpox. After the boy recovered from his own resulting cowpox, Jenner inoculated him with smallpox; the boy was immune. After Jenner published the results of this and other cases in 1798, the practice of Jennerian vaccination spread rapidly.
Louis Pasteur established the cause of infectious diseases and the medical basis for immunization. Pasteur formulated the germ theory of disease, the concept that disease is caused by communicable microorganisms. In 1880, Pasteur discovered that aged cultures of fowl cholera bacteria lost their power to induce disease in chickens but still conferred immunity to the disease when injected. He went on to use attenuated (weakened) cultures of anthrax and rabies to vaccinate against those diseases. The American scientists Theobald Smith (1859934) and Daniel Salmon (1850914) showed in 1886 that bacteria killed by heat could also confer immunity.
In 1888, Pierre-Paul-Emile Roux (1853933) and Alexandre Yersin (1863943) showed that diphtheria bacillus produced a toxin that the body responded to by producing an antitoxin. Emil von Behring and Shibasaburo Kitasato found a similar toxin-antitoxin reaction in tetanus in 1890, and von Behring discovered that small doses of tetanus or diphtheria toxin produced immunity, which could be transferred from animal to animal via serum. He concluded that the immunity was conferred by substances in the blood, which he called antitoxins, or antibodies. In 1894, Richard Pfeiffer (1858945) found that antibodies killed cholera bacteria (bacterioloysis). Hans Buchner (1850902) in 1893 discovered another important blood substance called complement (Buchner's term was alexin), and Jules Bordet in 1898 found that it enabled the antibodies to combine with antigens (foreign substances) and destroy or eliminate them. It became clear that each antibody acted only against a specific antigen. Karl Landsteiner exploited this specific antigen-antibody reaction to distinguish the different blood groups.
In the 1880s Russian microbiologist Elie Metchnikoff discovered cell-based immunity: white blood cells (leucocytes), which Metchnikoff called phagocytes, ingested and destroyed foreign particles. Considerable controversy flourished between the proponents of cell-based and blood-based immunity until 1903, when Almroth Edward Wright brought them together by showing that certain blood substances were necessary for phagocytes to function as bacteria destroyers. A unifying theory of immunity was posited by Paul Ehrlich in the 1890s; his "side-chain" theory explained that antigens and antibodies combine chemically in fixed ways, like a key fits into a lock. Until now, immune responses were seen as purely beneficial. In 1902, however, Charles Richet and Paul Portier demonstrated extreme immune reactions in test animals that had become sensitive to antigens by previous exposure. This phenomenon of hypersensitivity, called anaphylaxis, showed that immune responses could cause the body to damage itself. Hypersensitivity to antigens also explained allergies, a term coined by Pirquet in 1906.
Much more was learned about antibodies in the mid-twentieth century, including the fact that they are proteins of the gamma globulin portion of plasma and are produced by plasma cells; their molecular structure was also determined. An important advance in immunochemistry came in 1935 when Michael Heidelberger and Edward Kendall (1886972) developed a method to detect and measure amounts of different antigens and antibodies in serum. Immunobiology also advanced. Frank Macfarlane Burnet suggested that animals did not produce antibodies to substances they had encountered very early in life; Peter Medawar proved this idea in 1953 through experiments on mouse embryos.
In 1957, Burnet put forth his clonal selection theory to explain the biology of immune responses. On meeting an antigen, an immunologically responsive cell (shown by C. S. Gowans [1923 in the 1960s to be a lymphocyte) responds by multiplying and producing an identical set of plasma cells, which in turn manufacture the specific antibody for that antigen. Further cellular research has shown that there are two types of lymphocytes (non-descript lymph cells): B-lymphocytes, which secrete antibody, and T-lymphocytes, which regulate the B-lymphocytes and also either kill foreign substances directly (killer T cells) or stimulate macrophages to do so (helper T cells). Lymphocytes recognize antigens by characteristics on the surface of the antigen-carrying molecules. Researchers in the 1980s uncovered many more intricate biological and chemical details of the immune system components and the ways in which they interact.
SEE ALSO Antibody; Antigen; Homogeneous enzyme immunoassay (EMIT); Vaccines.