Anergy to Mycobacterium paratuberculosis.

If an individual fails to mount a successful CMI (T cell) reaction to an organism, then that it is known as an anergy reaction. The following are possible explanations for why some individuals may have an anergy reaction to Mycobacterium paratuberculosis.

Immuno-modulation.

Some mycobacteria actively interfere with the CMI reaction, notably Mycobacterium leprae and possibly Mycobacterium ulcerans. This immune interference phenomenon is known as immuno-modulation. The mechanism for how Mycobacterium leprae achieves this is unclear, but it is most likely that the organism produces cytokines that suppress immune action against the organism. This immuno-modulation suppresses the CMI reaction to M leprae in some individuals, and those individuals go on to develop aggressive lepromatous leprosy. In other individuals, immuno-modulation fails, and the sufferer is able to contain M leprae. The latter group develop contained tuberculoid leprosy.

Research has been conducted into whether M paratuberculosis is capable of immuno-modulation, for example in the study "Induction of suppressor cells by Mycobacterium paratuberculosis antigen in inflammatory bowel disease". This study describes clear evidence of immuno-modulation by M paratuberculosis in Crohn's disease patients, but is unable to tell what role this immuno-modulation may take in causing Crohn's disease.

In the case of tuberculosis, the immuno-modulation does not come from M tuberculosis, but may come from another source. For example, in AIDS patients, the HIV virus is known to have suppressed the patients population of T cells, thus preventing them from displaying a CMI reaction. If an AIDS sufferer is infected with tuberculosis, then that patient will suffer from the aggressive form of tuberculosis.

Malnutrition.

Malnutrition is a common and difficult problem for sufferers of Crohn's disease, since the disease affects the very parts of the body that are responsible for absorbing food, thus malnourishing the body and diminishing its ability to fight infection. This malnourishment may also be responsible for the failure of the CMI reaction of some Crohn's disease patients. The following is a reference to a study that studied the immune reactions of guinea-pigs to Mycobacterium bovis (a close relative of Mycobacterium tuberculosis), and finds that their CMI reaction to the bacterium is retarded by malnutrition. Further, the more malnourished they were, the weaker was their CMI response. "Cell-mediated immunity in malnourished guinea pigs after Mycobacterium bovis BCG vaccination".

Autoimmunity.

Another possible explanation for the failure of the CMI reaction is autoimmunity. Bacteria and humans are formed of proteins. The proteins for any given bacterium are often unique to that bacterium. In terms of the immune system and immune reaction, these proteins are known as antigens. The immune system uses these antigens to combat infections. Both T cells and B cells recognise antigens, and form other proteins, called antibodies, that bind to these antigens, thus rendering them harmless, and they can then be removed from the body (the antibody-antigen pair is known as an immune complex).

Some proteins (antigens) which make up mycobacteria are identical to proteins that exist in the human body. In some people, antibodies are formed against those antigens that are identical to human proteins (known as self-reactive antigens), and those antibodies will not only attack the infecting mycobacteria, but will also attack the tissues of the body that contain these antigens. These tissues may be far from the site of infection. This is how secondary inflammatory symptoms, such as arthritis or uveitis, come about. This phenomenon is known autoimmunity.

In other individuals, the body will not allow such self-reactive antibodies to exist, because they are harmful to the body, and destroys them, thus leaving the body with no antibodies with the infecting antigen.

Most species of mycobacteria share a high percentage of their antigens with humans. In the case of Mycobacterium tuberculosis, 65% of its antigens are shared with humans, i.e. 65% of the DNA of Mycobacterium tuberculosis is identical to human DNA.

Source: http://archive.crohn.ie/anergy.htm
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