Page 719 - Veterinary Immunology, 10th Edition

VetBooks.ir Immunity to Food

Dietary antigens are not normally antigenic as a result of oral
tolerance mediated by Treg cells. These peripheral Tregs (pTregs)

are abundant in the intestine. Under normal conditions, dietary
antigens generate small intestinal pTreg cells. These pTregs are
distinctly different from the pTregs produced in response to the
microbiota. For example, they are present in the intestine of germ-
free mice. They are short-lived but very potent suppressive cells.

There is evidence that a specialized subpopulation of intestinal
dendritic cells is also required to stimulate this pTreg production
and hence oral tolerance.

Secretory IgA responses are not usually generated against food
antigens. Likewise, soluble food proteins are unlikely to trigger TLR
responses. (Although TLR4-deficient mice readily develop food
allergies.)
Another mechanism by which oral tolerance may be induced is

through the production of “tolerosomes.” These are exosomes
produced by enterocytes. They carry MHC class II on their surface
and this binds antigenic peptides sampled from the gut lumen.

Purified tolerosomes fed to animals induce tolerance. It is suggested
that presentation of food antigens by tolerosomes induces Treg
formation.
It has been estimated that about 2% of ingested food protein is
absorbed as peptide fragments large enough to be recognized by

the immune system, although a very much smaller fraction of these
molecules (<0.002%) is absorbed intact. This protein reaches the
portal circulation, but little passes the liver and enters the systemic

circulation. Presumably the Kupffer cells of the liver capture blood-
borne food antigens. Antibodies produced locally may bind to this
adsorbed antigen and generate immune complexes that are
removed as the blood passes through the liver. If a calf is fed a
defined dietary antigen such as soy protein, although it is initially

well absorbed, the animal soon begins to make IgA antibodies to
soy. Once antibodies are produced, immune exclusion occurs, and
the amount of protein absorbed drops significantly. If another novel

protein is introduced into the feed, it too will be initially absorbed

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