Pathogenesis of Johne's Disease
Exposure
- Except under unusual circumstances infection of animals with M. paratuberculosis begins in the
first few months of life. This is because there is an age dependent increase in resistance as
animals grow older. Experimental evidence has shown, however, that the resistance is never
complete. Even adult animals, if given a sufficiently large dose of M. paratuberculosis bacteria
can become infected. But under normal animal husbandry conditions, exposure to such large
doses probably rarely occurs. This means, for example, that an infected adult dairy cow in a
stanchion or tie stall barn is not going to infect the cow standing next to her. Infected cows are
primarily just a source of infection for calves.
- The vast majority of infections in young animals are acquired by ingestion of M. paratuberculosis.
This happens accidentally when they consume manure containing the bacterium. Sucking on
manure contaminated teats on the udder of their mother, licking contaminated bars in the stall
where they are born, or being housed in a location where they have access to manure from the
adult herd are all ways young animals have opportunities to ingest this bacterium.
- A second method of exposure is by drinking infected milk. M. paratuberculosis is excreted in the
milk of infected lactating animals, particularly when the infection is in the more advance stages.
Thus, animals that spend a lot of time with their mothers and nurse naturally have the highest risk
of becoming infected. On dairies where calves are normally removed from cows and housed
separately, the practice of feeding whole milk instead of artificial milk replacers can result in
spread of M. paratuberculosis.
- The third, but least common, route of exposure is in utero. In the later stages of infection, the
M. paratuberculosis infection disseminates beyond the initial site of infection, the ileum. At that
time, if the animal is pregnant, the fetus can become infected. Infected fetuses can die and
spontaneously abort, or they could be born live and grow to become infected adults. How in utero
infections affect diagnostic tests on those animals that survive to adulthood is not known.
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- The primary site of infection is at a very specific site in the lower part of the small intestine known
as the ileum. The wall of the ileum contains a large number of pockets of lymphoid tissue known
as Peyer's patches that lie just beneath the interior surface of the intestine. Peyer's patches are
clusters of macrophages and lymphocytes that are organized much like in lymph nodes. Covering
Peyer's patches are a layer of cells called M cells. These cells function to circulate into the lumen
of the intestine where they ingest antigens before returning to the Peyer's patch to "show" these
antigens to the macrophages and lymphocytes. This is a means of "educating" the young animal
about its environment and is a protective mechanism designed to help the animal become
immune to pathogens in its environment.
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- Unfortunately, when M cells bring M. paratuberculosis to the Peyer's patch, the bacterium finds
an ideal place for growth. Macrophages in Peyer's patches engulf M. paratuberculosis with the
intention of destroying the foreign invader. For reasons that are unclear, macrophages fail in this
endeavor.
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- Inside a macrophage M. paratuberculosis multiplies until it eventually kills the cell and spreads
and infects other nearby cells. In time other parts of the ileum and, eventually, other parts of the
body are teaming with millions of M. paratuberculosis bacteria. How M. paratuberculosis neutralizes or
evades the normally efficient bacterial killing mechanisms of macrophages is not known.
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- The animal's immune system reacts to the M. paratuberculosis invasion by recruiting more
macrophages and lymphocytes to the site of infection. The lymphocytes release a variety of
chemical signals, called cytokines, in an attempt to increase the bacterial killing power of the
macrophages. Macrophages fuse together forming large cells, called multi-nucleated giant cells,
in an apparent attempt to kill the mycobacteria. Infiltration of infected tissues with millions of
lymphocytes and macrophages leads to visible thickening of the intestine. (See photo, 219.7K) Late in the infection,
antibody production by the animal occurs, but this has no effect on control of M. paratuberculosis
multiplication. In fact, detection of antibody to M. paratuberculosis in serum of animals is an
indicator that clinical signs of disease and death from the infection will soon follow.
- It is not known how often spontaneous recovery from infection occurs, if it occurs at all. It
appears that most infections slowly and inevitably progress until the animal dies from the
pathology induced in the intestine. More detail on the host response to M. paratuberculosis
infection and how this affects intestinal function is described under the pathology topic of FYI.
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Last revised February 19, 1997.
URL is http://www.vetmed.wisc.edu/pbs/johnes/pathogen.html.html.
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