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Proteins, Immune Activity , Allergy
Proteins are the most active molecules in immune defense and hypersensitivity disease. The antigens that excite immune responses are mostly proteins and the antibodies that identify antigens are proteins.
The original concept of allergy included all immune-mediated disease and the term allergy was interchangeable with the term "hypersensitivity." Allergy can be thought of as hypersensitivity disorders with external causes. Substances that trigger allergic responses are antigens. These are often proteins that can be found in air, food and water. Airborne antigens such as plant pollens or house dust are well known. Other airborne antigens and food antigens are less obvious. New and foreign substances introduced to the body such as drugs and herbs cause allergic reactions
Immediate reactions are triggered by specific proteins. These proteins can be isolated from foods and are used to skin test sensitive individuals. Specific protein antigens have been characterized from a variety of foods, particularly cow's milk, eggs, soybeans, peanuts, fish, crustaceans, wheat, oats, corn, rice, citrus, and some other foods. Gelatin is a collection of animal proteins made from skin and bones that can trigger typical type allergy. Reactions to gelatin-containing foods do occur. Reactions to gummy bears, jello, licorice, marshmallows, fruit yogurt, instant whipped cream, and puddings are examples. Delayed immune responses to food proteins often occur when food proteins enter the body.
The digestive tract is the major portal of entry into body spaces. Substances entering the tract are usually tolerated by an active process that suppresses immune responses. If tolerance fails to specific proteins, for example, these proteins trigger inflammatory immune responses and disease develops. This is the basis of food allergy. Infants begin life with little food tolerance and develop tolerances over many months with gradual introduction of new foods. Failure of tolerance mechanisms is common in infants so that food allergy is one the most common health problems in the first year. Tolerance that develops early in life may be partial or complete but is unstable through the life of an individual.
The immune sensors in the digestive tract must distinguish among thousands of potential antigens every day, responding to a few that represent potential threats and ignoring the rest. This is not an easy task. Protein antigens make their way through the intestinal epithelium into the lamina propria below. There, dendritic cells combine with antigens and some migrate to the regional lymph nodes. Some suggest that dendritic cells in villous lamina propria account for most of the protein uptake from the intestine. Migration of dendritic cells from the lamina propria to MLN is required for the induction of oral tolerance. It is likely that inflamed digestive tracts leak in many places allowing large amounts of peptide antigens enter into body spaces, lymphatic channels and the blood.
Antibodies are serum proteins or immunoglobulins. These proteins can be appreciated as a memory system that detects antigen and then links antigen to an effector system. Antibodies have a sensing end or antigen recognition site, the tips of the y-shaped molecule which encode antigen recognition in the hypervariable region. Antibodies also have action sites that activate complement and/or phagocytic cells, the effector system. Antibodies may be free-floating in the serum and combine with antigen to form immune complexes. Alternatively, antibodies may be attached to cell-surface antigens, acting as receptors. Antibodies attached to bacterial cell-surface antigens will activate complement or attract phagoctytic cells to trigger bactericidal action. Antibodies attached to normal cells may attract killer t-cells that will attack and destroy the cell. Normal cells infected with viruses will display viral protein antigens on the surface and invite self-destruction; this is a form of altruistic suicide. Food antigens such as food proteins may also be displayed on cell surfaces and invite destructions. This is the cytotoxic option in food allergy.
Chirdo FG, Millington OR, Beacock-Sharp H, Mowat AMcI. Immunomodulatory dendritic cells in intestinal lamina propria. Eur J Immunol 2005; 35: 1831-1840. This is the first paper to demonstrate that orally administered protein antigens are taken up efficiently by dendritic cells in lamina propria and reports that these dendritic cells may be tolerogenic
Worbs T, Bode U, Yan S, et al. Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells. J Exp Med 2006; 203:519-527.
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