Immune Defenses of the Digestive
System
It has often been
emphasized that the digestive system “tube” is the host to a very hostile
intraluminal environment that is actually not part of the organism itself. This
tube includes microorganisms and chemicals that if not kept in check can
quickly result in the patient’s death. It is critical for health that the
luminal organs have mechanisms that are highly selective in identifying foreign
antigens and thus prevent the invasion of luminal microorganisms through or
between epithelial cells into the submucosa, where they can invade the rest of
the body. This system must also be able to distinguish between harmless
commensal organisms and organisms that cause disease. The extensive,
specialized system of immune cells that constantly defend against luminal
attack with a perpetual state of controlled inflammation described in this
section is known as the GALT system. If the GALT system is not effective,
microorganisms can invade; if it is overly active, autoimmune disorders result,
such as chronic gastritis, celiac disease, or inflammatory bowel disease. Other
defense mechanisms are discussed with Plates 1-50, 1-51, 1-53, and 1-54.
Epithelial cells provide the first line of both mechanical and immune
defenses. This is possible because the cells not only have specialized
qualities that prevent fluid and bacterial movement through or between cells,
but they can also process antigenic material and function as antigen-presenting
cells.
Lymphocytes are the next line of defense in the digestive system. In
fact, there are over a trillion immune-active cells in the gut, making it by
far the largest lymphoid organ in the body. A fascinating, distinct subclass of
lymphocytes, the intraepithelial lymphocytes, migrate into the intercellular
space between epithelial cells. There they provide an important cytotoxic and
antiviral line of defense but play little, if any, role in processing the immune response cascade. This is achieved by
a wide variety of lymphocytes, macrophages, and dendritic cells found in the
lamina propria of the intestinal organs, and to a lesser extent in the stomach.
The esophagus has lymphocytes, but in a normal state has no eosinophils, mast
cells, or polymorphonuclear cells.
Terminally differentiated B lymphocytes become plasma cells in the lamina
propria, where they are the major source of IgA. IgA synthesized in the gut can
be released in monomers into the circulation. IgA is also secreted into the
lumen of various organs, including the gut, as secretory IgA in the form of
dimers, which are two IgA molecules coated with a specialized secretory
component that prevents enzymatic digestion. Secreted IgA dimers are kept near
the surface by becoming trapped in the mucus glycocalyx. Intraluminal secretory
IgA that reaches the distal ileum can be reabsorbed and transported to the
Kupffer cells of the liver, where the antigen can be destroyed and the
secretory IgA released into the bile, and thus circulated back to the
intestinal lumen.
Dispersed between epithelial cells of the small intestine can be found
highly integrated antigen-processing structures consisting of modified microfold
epithelial cells (M cells) and their
adjacent lymphoid follicles, or Peyer patches. A Peyer patch is a highly active
accumulation of macrophages, dendritic cells, and T and B lymphocytes which can
evaluate antigens and even whole microorganisms brought across the epithelium
through the porous M cells and their adjacent specialized epithelial cells.
Submucosal dendritic cells independent of M cells also play a key role as
antigen- presenting cells. Once activated, B-cell and T-cell blasts can leave
the Peyer patch and enter the circulation or be carried by the lymphatics to
adjacent nodes or to the bloodstream.
Another important part of the immune defense systems for the digestive
system are the large numbers of lymph nodes found throughout the mesentery and
the larger accumulations of lymph glands at the base of the three major sources
of arterial blood to the gut, the celiac, superior mesenteric, and inferior
mesenteric arteries.
Finally it must be remembered that the liver is second only to the small
intestine as the second largest reticuloendothelial organ in the body. Antigens
and microorganisms that escape other gut defenses are carried to the liver,
where they can be filtered from the blood by sinusoidal Kupffer cells.
