The Pathology of Mycobacterial Diseases.
Well known human diseases that are caused by mycobacteria are tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by Mycobacterium leprae. In common with all mycobacterial diseases (known as mycobacterioses), these diseases come in two forms, the contained form and the aggressive form, known as the "polar" forms of the disease.
The Contained form.
The contained form of leprosy is known as tuberculoid leprosy and the contained form of tuberculosis is simply known as the contained form of tuberculosis. People who suffer from the contained forms of mycobacterioses are known to mount only a "Cell Mediated Immunity" (CMI) response to the infecting mycobacterium. This CMI response is activated only by T cells. Sufferers do not mount an "Humoral" response to the invading mycobacterium.
This most recognisable symptom of the contained form is the formation of Granulomas. Granulomas are formed when an invading mycobacterium, possibly living inside an infected host cell, is surrounded by T cells. First a layer of CD4 T cells surrounds the mycobacterium, and then a layer of CD8 T cells surrounds the layer of CD4 T cells. This has the effect of forming a hard lump (known as a "tubercle" in tuberculosis) around the mycobacterium, from which it cannot escape to further infect the body. Tissue damage around these granulomas can be extensive, especially if they occur in highly sensitive areas of the body, such as nerve cells, or the lymph nodes. If formed in the intestines, they lead to the formation of "strictures", which restrict free passage of food through the intestines. In "tuberculoid leprosy" sufferers, these granulomas are seen as lumps in the skin, and can restrict the flow of blood to extremities (fingers, toes, etc.)
The contained forms of mycobacterioses are characterised by the presence of very few numbers of the infecting mycobacteria compared to the damage caused.
The Aggressive form.
The aggressive form of leprosy is known as "lepromatous leprosy", and the aggressive form of tuberculosis is known as "miliary tuberculosis". People who suffer from the aggressive forms of mycobacterioses are known to mount only an "Humoral" response to the infecting mycobacterium. This Humoral response is activated only by B cells. They do not mount a "Cell Mediated Immunity" (CMI) response to the invading mycobacterium.
Common symptoms of the aggressive forms of mycobacterioses are perforation, fistulisation of the infected organs and abscess formation. Perforation leads to holes in the infected organs, leading to a breach of the integrity of body cavities. A fistula is a growth of tissue from one organ to another. For example, a fistula may connect the intestines to the bladder, or to the external skin of the sufferer. If untreated, miliary tuberculosis will almost certainly result in the death of the sufferer.
The aggressive forms of mycobacteria are characterised by the presence of large numbers of the infecting mycobacteria, which rage uncontrolled in the infected host.
Autoimmunity.
A possible cause of these failures of the CMI response or of the humoral response is autoimmunity. Some proteins (known as antigens) which make up mycobacteria are identical to proteins that exist in the human body. The immune system uses these antigens to combat infections. Both T cells and B cells recognise antigens, and form other proteins (antibodies) that bind 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). If antibodies are formed to antigens that are identical to human proteins (known as self-reactive antigens), then those antibodies 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 some individuals, the body will not allow such self-reactive antibodies to exist, because they are harmful to the body, and destroys them. This is known as an anergy reaction.
A full spectrum of reactions.
In practice, mycobacteriosis patients seldom exhibit the extreme contained or aggressive forms described above, but exhibit a form that is a hybrid of the two. For example, "borderline leprosy" is a form of leprosy that exhibits symptoms from both tuberculoid and lepromatous leprosy.
Immunology.
Immunology research, where researchers seek to measure the bodies immune response to various bacterial antigens, are highly specific. Most research looks for an humoral response or for a CMI response. As can be seen from the above, a search for a CMI (T cell) response to mycobacterial antigen will show a response in sufferers of the contained form, but will show no response in sufferers of the aggressive form. Likewise, a search for an humoral (B cell) response will show a response in sufferers of the aggressive form, but no response in sufferers of the contained form. Statistical analysis of results of such searches, without first dividing the patients into two groups that represent the different forms, will yield random results.