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- Understand the role played by the mucosal immune system in protecting the host from infections acquired via the oral route while failing to respond to innocuous antigens
- Define the mechanisms and relative roles of innate versus adaptive immunity
- Understand the specialized features of the mucosal immune system compared with immunity expressed in the periphery
- Identify the cell populations that contribute to immunity in the gut and their locations
- Describe mechanisms that result in cellular homing to the gut and other mucosal sites
- Describe the characteristics of IgA that make it especially suited to function in the gut
- Describe the immune responses that occur to antigens encountered in the gut
- Understand the concept of oral tolerance
- Understand the origins, make-up and physiological importance of microbial populations that exist in the normal intestine
- Define the consequences of abnormal immune responses in the intestine
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Concept of a Mucosal Immune System
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As we have learned in previous chapters, the surface of the gastrointestinal tract represents a vast frontier that can potentially serve as a portal of entry into the body. Moreover, by the very nature of the physiological function of the gut, its lumen is frequently filled with a complex mixture of nutrients that constitute an attractive “culture medium” for a variety of microbes. Indeed, the intestine is challenged to distinguish between potentially harmful microorganisms, against which it must defend itself, versus the innocuous antigens that occur in food. The intestine also has a special need for immune surveillance against malignancy. Thus, the rapid rate of proliferation of intestinal epithelial cells, coupled with exposure of these cells to potential toxins in the intestinal lumen, renders the epithelium uniquely sensitive to cell transformation. It is likely that the immune system is important in detecting many transformed cells before they have the opportunity to develop into a tumor, although clearly this line of defense is not perfect. Finally, over millennia, humans and other animals have been exposed to a barrage of intestinal pathogens via contaminated food and water; inadequate sanitation still persists in many underdeveloped areas of the world. This constant exposure has driven the development of a highly specialized branch of the immune system, referred to as the mucosal immune system, which encompasses the mucosa-associated lymphoid tissues, or MALT.
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In fact, the intestine represents the largest immunological compartment of the body, and has also evolved nonimmunologic barriers to invasion by pathogens. The nonimmune barriers include secretion of the acid by the stomach, the potential antimicrobial actions of other components of the digestive juices such as enzymes and bile acids, the mucus layer, which overlies much of the epithelium, that limits microbial attachment to the epithelial surface, specific antibacterial products secreted by specialized epithelial cells or by the salivary glands, and the epithelium itself, which, when intact, represents a physical barrier to the uncontrolled flux of microbes into the body. The immune barriers include both the so-called innate immune system, and adaptive, ...