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The gastrointestinal immune system


Introduction

As described in Chapter 8 , the immune system is a complex cellular network that defends the body against danger. To do so, the immune system must distinguish between safe and dangerous substances.

  • Safe or nonthreatening substances can be part of the body itself (e.g., normal extracellular molecules, cells, and tissues) or foreign (e.g., foods and commensal bacterial).

  • Dangerous materials can be part of the body (e.g., cancer cells) or foreign (e.g., pathogenic bacteria, viruses, and parasites).

With each meal, we ingest an enormous number of nonself molecules, many of which are potential antigens. Thus the enteric immune system is one of the largest tissue-specific immune organs in the body, as it must defend the enormous surface area of the gastrointestinal (GI) tract.

Enteric immune system structure

The immune system of the GI tract can be divided into “nonimmunologic” and “immunologic” defenses.

  • Nonimmunologic defenses

    • Mechanical barriers (epithelial cells, the mucous layer of the GI tract called the glycocalyx)

    • Mechanical actions (the peristaltic movement of the GI tract)

    • Components of GI secretions (gastric hydrochloric acid)

    • Commensal or symbiotic nonpathogenic GI microorganisms (which compete with potential pathogens for space and nutrients)

  • Immunologic defenses

    • Immune cells that either reside in or patrol the GI tract

    • Immune system molecules produced by such cells

Gastrointestinal immune system tissues

Nonimmune tissues

The epithelial lining is arguably the most important nonimmune tissue component of the GI defenses.

  • In the oral cavity stratified, squamous epithelial lining prevents microorganisms from penetrating into deeper tissues.

  • In the stomach, small intestine, and large intestine, epithelial cells held together by tight junctions provide a similar barrier through which antigens cannot pass ( Fig. 27.1 ).

    Fig. 27.1, Tissue and cellular components of the gastrointestinal (GI) immune system. Nonimmune defenses, such as the mucus layer and epithelial layer, are present throughout the GI tract. Innate immune cells, such as antigen-presenting cells (macrophages and dendritic cells) and mast cells, are present in the lamina propria. Adaptive immune system T cells, B cells, and plasma cells are found scattered among epithelial cells, in the lamina propria, or in the context of gut-associated lymphoid tissue (GALT), such as lymphoid follicles. Clusters of lymphoid follicles form Peyer’s patches.

Immune tissues

The gut-associated lymphoid tissue (GALT) is composed of innate and adaptive immune cells arranged in a pattern similar to that in lymph nodes and the spleen. GALT is located throughout the GI tract in the lamina propria, just beneath the epithelial lining.

  • The tonsils are the largest GALT of the oropharynx and can be seen on physical examination.

  • Peyer’s patches are found throughout the small intestine, although the majority of them are found in the ileum and jejunum. they contain 200 to 400 lymphoid follicles.

  • The large intestine does not have Peyer’s patches but does have numerous GALT follicles. The appendix especially has large aggregates of such lymphoid tissue.

Mesenteric lymph nodes are typical lymph nodes located in the gut mesentery. Lymphatic channels form the lamina propria of the small intestine (called lacteals) lead to mesenteric lymph nodes.

Gastrointestinal immune system cells

Nonimmune cells that contribute to host defense of the GI tract include commensal bacteria and other nonpathogenic microorganisms. Among immune cells, both innate and adaptive immune cells protect the GI tract.

  • Some are resident cells stationed among epithelial cells or in the lamina propria.

  • Others circulate through the body, exiting the blood at high endothelial venules to patrol the GI mucosa in search of pathogens, and then entering the lymphatic system to return to the blood.

Nonpathogenic bacteria

The intestinal tract is sterile at birth but is soon colonized in an oral-to-anal direction. The trillions of microorganisms making up the normal enteric flora or “microbiome” is influenced by diet and medications. These microorganisms live symbiotically with the human host, receiving a steady supply of nutrients while producing substances useful to the host (such as vitamin K) and preventing the colonization and penetration of the alimentary tract of pathogens by competing with them for space and resources (see Clinical Correlation Box 27.1 ).

Fast Fact 27.1

An estimated one-fourth of the cells of the intestinal mucosa are lymphoid cells.

Approximately 70% of the body’s antibody-secreting B cells are located in the intestine. About 5×10 10 immune cells reside in the gastrointestinal tract, equal to the number in the bone marrow.

Clinical Correlation Box 27.1

The importance of the normal gut flora in protecting against infection can be seen in patients who are given antibiotics. In addition to killing the bacteria that are causing infection in the person, these antibiotics also kill the normal enteric flora. This allows pathologic species of bacteria to colonize the gut. The classic example of this is colonic proliferation of Clostridium difficile, which may cause an inflammatory condition called pseudomembranous colitis when the normal flora is disrupted following the use of antibiotic medications. C. difficile is normally present in low numbers, but its overgrowth contributes to greater synthesis of toxins that damage the colonic epithelium resulting in colitis and diarrhea.

Innate immune cells

Antigen-presenting cells (APCs) include:

  • Macrophages.

  • Dendritic cells reside in the lamina propria of the gastric mucosa and can extend portions of their membrane into the gut lumen to sample antigens.

  • Mast cells.

The top of each Peyer’s patch is covered by a specialized epithelial cell known as a microfold or M cell. M cells sample luminal contents and shuttle these antigens into the Peyer’s patches via transcytosis ( Fig. 27.2 ).

  • M cells do not contain specific receptors to bind antigens.

  • Rather, they are located in pits where antigens are likely to deposit, and they are not covered with secretory immunoglobulins (see later) that prevent the binding of antigens.

  • Thus M cells sample a large percentage of gut antigens.

Fig. 27.2, Cellular structure of a Peyer’s patch. The luminal “cap” of the patch is composed of M cells that transport luminal contents into the lamina propria via transcytosis. There, antigen-presenting cells, such as dendritic cells and macrophages, digest and present antigen to T cells. The germinal center of a Peyer’s patch has a central area of B cells and a surrounding area of T cells.

Kupffer cells

As described in Chapter 26 , the liver removes damaging chemicals and potentially toxic compounds from the blood. Most intestinal venous blood enters the liver via the portal circulation, carrying the wide array of potentially infectious microbes and other antigenic materials that bypass the GI tract defenses and would enter the circulation. Kupffer cells are fixed (i.e., noncirculating) macrophages located within the liver sinusoids. They engulf many soluble antigens from the portal circulation.

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