Immunology icon Immunology Notes

Some Topics

  • Antibodies = Immunoglobulins

    Antibodies are serum proteins or immunoglobulins. These proteins comprise a memory system which detects antigens and then links antigens to an effector system that defends against the antigen and associated structures. Antibodies are secreted by B-lymphocytes ( transformed to plasma cells in tissue spaces). Antibodies may be free-floating in the blood and combine with antigen to form immune complexes.

    The sensing ends of antibodies form an antigen recognition site - the tips of the y-shaped molecule which encode antigen recognition are known as the hypervariable region. Antibodies also have action sites which activate complement and/or phagocytic cells - the effector system. Antibodies attaching to bacterial cell-surface antigens, for example, will activate complement or attract phagocytic cells to cause bactericidal action.

    B Lymphocytes originate in the bone marrow and migrate to lymphatic tissues throughout the body. The main sites of serum antibody production are the spleen, lymph nodes and mucosa associated lymphatic tissues. In young children, serum immunoglobulins increase in concentration and variety as they grow, an indication of expanding acquired immunity and hypersensitivity to a variety of potential antigens that arrive from the environment. Infants inherit some antibodies from their mothers, but face an onslaught of antigens that their immune cells must learn to recognize. Estimates of the number of distinct antibodies present in an adult human are up to a million or more.

    Antibodies can be very specific to one antigen target and are used extensively in biological research to locate and mark target molecules. Target-specific antibodies developed from a single clone of B lymphocytes are referred to as monoclonal antibodies. The manufacture of antibodies for research and therapy is big business. More than 25,000 antibodies are offered to researchers and several are used to treat human diseases. The basic technique of production is to immunize mice with well chosen antigens and harvest B lymphocytes from the animals. Cells making the desired antibody are then selected and fused with long-lived cells that will live in culture media and continually produce antibody. New methods are being developed to produce antibodies in more efficient, less expensive ways.

    There are 5 main antibody types:

    IgA: circulating and secreted on all defended body surfaces, as the first defense against invaders. Secretory (s IgA) is found in large amounts in breast milk, saliva, and gastrointestinal secretions. IgA may be an important and effective antibody in sites other than mucosal tissues, such as the central nervous system. IgA inhibits the binding of micro-organisms to mucosal surfaces, preventing entry. IgA plays a similar role in reducing antigen entry through mucosal surfaces. sIgA deficiency is associated with increased gastrointestinal tract permeability and increased manifestations of delayed patterns of food allergy.

    IgD: surface receptors on lymphocytes.

    IgE: the antibody which produces typical allergy or immediate hypersensitivity reactions such hay fever, asthma, hives, and anaphylaxis. Its "normal" function seems to be in anti-parasite defense. This class of immunoglobulins is distributed throughout the body, although the cells synthesizing IgE are predominantly found in association with mucosal tissues. IgE attaches to mast cells and acts as a receptor to antigen. IgE-bearing cells are found in large numbers in the neonatal GALT, which on maturation revert to IgA and IgM synthesis. Little is known of the traffic of IgE-bearing or IgE-producing cells. If there is traffic of IgE cells it is less extensive than the IgG system ; IgE is not found in breast milk, and only in very low amounts in other secretions such as saliva.

    IgG is the major circulating antibody which enters tissues freely, and participates in diverse immune events. The IgG antibodies represent a large vocabulary of antigen recognition molecules. There are four subgroups, currently labeled with number suffixes, (IgG1 to 4). In some mucosal tissues (e.g. mammary glands of ruminants), the IgG1 class of immunoglobulin-producing cells predominates. IgG ( and IgM) activate complement.

    IgM: the multivalent antibody, capable of capturing and binding antigens to form large insoluble complexes which are readily cleared from the blood. The isohemagglutinins (anti-A, anti-B), rheumatoid factor, and antibodies to micro-organisms are IgM. IgM levels may be elevated in patients with delayed patterns of food allergy, and probably manifest a protective defense response.

    IgA Deficiency

    Secretory IgA is essential to mucosal surface defenses and deficiency of this antibody impairs antigen-exclusion mechanisms. Patients with IgA deficiency are likely to have increased gut permeability to antigens and may show increased evidence of delayed patterns of food allergy and diseases that are related to type 3 and 4 mechanisms - i.e. the "autoimmune diseases". An increased incidence of celiac disease, rheumatoid arthritis, SLE, pernicious anemia, pulmonary hemosiderosis has been reported in IgA deficient patients. There is increased incidence of antibodies to food antigens. The diet of patients with IgA deficiency require adaptive revision - if symptoms develop the therapeutic strategy is to reduce food antigen loading to compensate for increased antigen entry. This can be done with the Alpha Nutrition Program approach to diet revision. A complete solution to IgA deficiency disease is to replace food with an elemental nutrient formula that provides all nutrients in the absence of antigens.