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The Immune System / What is The Immune System?
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submitted by Dr. Gary Farr - Contact the author here.
Last Updated December, 31, 2007
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Mounting an Immune Response
 Infections remain the most common cause of human disease. Produced by bacteria, viruses, parasites and fungi, infections may range from relatively mild respiratory illnesses such as the common cold, to debilitating conditions like chronic hepatitis, to life-threatening diseases such as AIDS and meningitis.
To fend off the threatening horde, the body as devised astonishingly intricate defenses. Microbes attempting to enter the body must first find a chink in the body's external protection. The skin and the mucous membranes that line the body's portals not only pose a physical barrier, they are also rich in scavenger cells and IgA antibodies.
Next, invaders must elude a series of nonspecific defenses-those cells and substances equipped to tackle infectious agents without regard for their antigenic peculiarities. Many potential infections are cut short when microbes are intercepted by patrolling scavenger cells or disabled by complement or other enzymes or chemicals. Virus-infected cells, for instance, secrete interferon, a chemical that rouses natural killer cells. For detailed information about the immune response go to this page.
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A Billion Antibodies
Scientists were long puzzled by the opulence of the immune system's resources. The body apparently could recognize and mount unique responses to an endless variety of antigens-but how in the world could all that information be crammed into a limited number of genes?
The answer came as a surprise. A typical gene consists of a fixed segment of DNA, which directs the manufacture of a given protein molecule such as insulin. Antibody genes, in contrast, are assembled from bits and pieces of DNA scattered widely throughout the genetic materials. As the B cell matures, it rearranges or shuffles these gene components, picking and choosing among hundreds of DNA segments-some for each of the antibody's variable (V), diversity (D), joining (J), and constant (C) regions. Intervening segments of DNA are cut out; the selected pieces are spliced together.
The new gene-and the antibody it encodes-are virtually unique. When the B cell containing this uniquely rearranged set of gene segments proliferates, all its descendants will make this unique antibody. Then, as the cells continue to multiply, numerous mutants arise; these allow for the natural selection of antibodies that provide better and better "fits" for the target antigen. The result of this entire process is that a limited number of genetically distinct B cells can respond to a seemingly unlimited range of antigens.
A similar mechanism was found to control a comparable structure of the T cell, the T cell's antigen receptor. The variable regions of T cell antigen receptors, like those of antibodies, are encoded by V, D, and J segments originally far apart, but which are brought together and fused into a single gene. With numerous candidates for each segment, the number of possible combinations becomes astronomical. However, in contrast to antibody genes, T cell receptor genes do not mutate as the T cells proliferate. This ensures that the self-tolerance imposed in the thymus will not be overthrown by the inadvertent generation of mutant T cell receptors that are anti-self.
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