What causes tuberculosis?

The causative agent of tuberculosis is mycobacterium tuberculosis. Although "consumption" as a disease was known even in ancient times, for a long time a persistent struggle of opinions of various scientists on the etiology of the disease continued before the causative agent of tuberculosis was discovered. The infectious character of tuberculosis was experimentally proved long before the discovery of the causative agent of the disease. The French scientist Wilmen in 1865 infected rabbits with tuberculosis by subcutaneous administration of tissues of affected organs and by inhalation of sputum smear of tuberculosis patients.

In 1882, Robert Koch succeeded in detecting a rod in the tubercle foci when the drug was stained with methylene blue and obtaining a pure culture of the pathogen. Scientists have established that mycobacterium tuberculosis is highly resistant to the effects of any physical, chemical and biological agents. Having found themselves in conditions favorable for their development, mycobacterium tuberculosis can long remain viable and virulent. They tolerate prolonged cooling and drying. In dry form, at a low temperature, in the dark, in the sewage waters of mycobacterium tuberculosis live about 300 days. In the corpses remain alive up to 160 days, and under the influence of sunlight perish only 6-8 hours. According to Yu.K. Weisfaler, mycobacterium tuberculosis multiplies by simple transverse division under favorable conditions, in other cases - by disintegration into grains. Thus, from old calcified foci, M.B. Ariel isolated granular and acid-resistant forms, and in the wall of the cavern (the most active tubercle focus), this author discovered reproduction by simple transverse division. In the process of development, tubercle bacilli may change their morphological properties under the influence of the environment.

On the basis of modern data, a whole doctrine about the causative agent of tuberculosis has been created, which significantly expanded and in many ways changed the idea of its role in the pathogenesis of the disease. The causative agent of tuberculosis (according to modern classification) is referred to the order of Actinomycetales, to the family Mycobacteriaceae, to the genus Mycobacterium. The existence of various morphological forms of mycobacterium tuberculosis and a large range of variability of their biological properties are noted.

On the basis of differences in biological properties, especially pathogenicity for humans and various animal species, four types of tuberculosis pathogens are differentiated:

• M. Tuberculosis, M. Bovis - highly pathogenic for humans;
• M. Avium causes diseases in birds and white mice;
• M. Microti (Oxford vole strain) - agent of tuberculosis of field mice.

M. Tuberculosis and M. Bovis can cause disease in humans as well as in many animal species: cattle, goats, sheep, horses, cats, dogs, etc. These mycobacteria have a peculiarity: sick animals can infect humans, and vice versa. Tuberculosis of the respiratory system in children often causes the appearance of M. Tuberculosis. Infection of children with bovine mycobacteria occurs mainly with the consumption of raw milk from sick animals.

The disease develops as a result of the complex interaction of the microbial factor and macroorganism under certain social and environmental conditions. With the development of tuberculosis, the importance of social factors is especially great. The causative agent of tuberculosis penetrates the body of the child under various conditions in various ways. The entrance gates of infection are more often the mucous membrane of the mouth, tonsils, less often other organs. Accordingly, the primary focus of inflammation has a different localization. It is possible and intrauterine infection of tuberculosis with specific placenta damage against the background of widespread tuberculosis in pregnant women or at the time of delivery with ingestion of infected amniotic fluid. Skin is the most difficult organ of tuberculosis. Mycobacteria can penetrate into the lymphatic pathway only through the damaged areas of the skin. Such cases of infection are described by medical workers at the autopsy of people who died of tuberculosis. Infection with mycobacteria is possible with poorly sterilized instruments (inoculated primary tuberculosis). In 1955 R. Radanov studied the health of 11 such children in Plovdiv (Bulgaria) after intramuscular injection of benzylpenicillin using improperly sterilized reusable syringes, which had previously been administered an anti-tuberculosis vaccine. In 1985, 21 newborns in the Orenburg maternity hospital were infected with tuberculosis by injecting immunoglobulin with syringes, which were used for injections into a child with congenital tuberculosis. In most children 3-4 weeks after the introduction of the medicine on the buttock, an infiltrate with a lesion of the regional inguinal lymph nodes as a typical primary tuberculosis complex developed at the site of the injection. A part of children underwent lymphohematogenous dissemination, up to the development of miliary tuberculosis.

Primary infection is most often accompanied by the emergence of a lesion in the hilar lymph nodes and lungs. Mycobacteria cause the development of a foci of necrosis, around it there is an inflammatory process: the migration of leukocytes, the accumulation of epithelioid cells, the giant cells of Pirogov-Langhans and lymphocytes. Thus, an epithelioid tubercle with a necrotic center is formed. On the periphery of this specific area there is a zone of nonspecific inflammation. Reverse development of the tubercle tubercle may be accompanied by complete resorption, however, fibrosis transformation and calcification often occur. Such an outcome is not considered complete healing, as calcicates often contain live mycobacterium tuberculosis. Under adverse conditions, especially in cases of uneven calcification, the focus can become a source of exacerbation of the disease. Nonspecific or paraspecific tissue processes are characterized by diffuse and nodular macrophage reaction, histiocytic lymphocytic infiltration, nonspecific vasculitis, fibrinoid necrosis, developing in the lungs, lymph nodes, heart, kidneys, liver, endocrine glands, synovial membranes, nervous system and leading to development sclerosis.

Already in the early phases of primary tuberculosis the neuroendocrine system suffers, which leads to profound functional shifts, aggravating the disorganization of the physiological processes of the organism. The emergence of secondary (after primary) tuberculosis is possible both as a result of superinfection (exogenous pathway) and as a result of reactivation of old foci - the remains of primary tuberculosis (endogenous pathway). The question of the endogenous and exogenous pathways for the spread of secondary tuberculosis can not be solved unambiguously. In some cases, both ways have a definite value in the onset of the disease. With repeated exogenous infection, conditions for exacerbation and progression of the tuberculosis process are created. With massive reinfection, dissemination of mycobacteria and the formation of multiple foci in the lungs and other organs are possible.

The morphological expression of primary tuberculosis is the primary tuberculosis complex, consisting of three components:

• hearth lesions in the organ - primary focus;
• tuberculosis inflammation of the lymphatic vessels - lymphangitis;
• tubercular inflammation of regional lymph nodes - lymphadenitis.

When airborne infection in the lungs, the primary tubercular focus (affect) occurs subpleurally in the most well aerated segments, more often the right lungs - III, VIII, IX, X (especially often in the III segment). It is represented by the focus of exudative inflammation, and the exudate quickly undergoes necrosis. A focus of caseous pneumonia is formed, surrounded by a zone of perifocal inflammation. Dimensions of the affect are different: sometimes it is the alveolitis, barely discernible microscopically, but more often the inflammation covers the acinus or lobule, less often the segment, in very rare cases the entire lobe. Constantly detect involvement in the inflammatory process of the pleura with the development of fibrinous or serous-fibrinous pleurisy.

Very quickly, a specific inflammatory process spreads to the lymphatic vessels adjacent to the primary focus - tuberculous lymphangitis develops. It is represented by lymphostasis and the formation along the lymphatic vessels in the perivascular edematous tissue of tubercular tubercles. It forms a path from the primary focus to the basal lymph nodes.

In case of alimentary infection, the primary tuberculosis complex develops in the intestine and also consists of three components. In the lymphoid tissue of the lower part of the jejunum and the cecum, tubercle tubercles with necrosis and subsequent formation in the mucosa of the ulcer are formed, considered as a primary affect. Further, there is tuberculous lymphangitis with the appearance of tubercles along the lymphatic vessels and caseous lymphadenitis of regional lymph nodes to primary affect.

There are three possible variants of primary tuberculosis:

• attenuation of primary tuberculosis and healing of foci of the primary complex;
• progression of primary tuberculosis with generalization of the process;
• chronic course (chronically current primary tuberculosis).

Advances in theoretical and methodological immunology allowed researchers to characterize systemic and local changes in immunological reactivity in the tuberculosis process quite fully. Primary infection with tuberculosis causes immunologic reorganization - the body becomes sensitive to tuberculin, develops tuberculin hypersensitivity of delayed type. It is now recognized that delayed-type hypersensitivity, the main component of the cellular immune response, is the leading factor in immune mechanisms in tuberculosis.

The outcome of the meeting of mycobacteria tuberculosis and macroorganism depends on the massive infection, the virulence of the infection, as well as the state of the body's immune system, its natural resistance. At primary infection in most cases there is an inhibition of growth of mycobacteria and their destruction. Mycobacterium tuberculosis is an optional intracellular parasite, in the body it is mainly found in the phagosome of macrophages. The complexity of the antigenic structure of mycobacteria (more than 100 antigenic structures) and the change in its composition over the course of the life cycle allow the mycobacteria to adapt effectively to coexistence with the cells of the host's immune system, to prolonged stay in the body with a change in the phases of extra- and intracellular parasites. Mycobacteria not only adapt to coexistence with the cells of the immune system, but also have a negative impact on it. It has been established that mycobacteria of tuberculosis synthesize an enzyme inhibiting the fusion of the phagosome with lysosomes. The ability of mycobacteria to reduce the expression of antigens of the first and second classes of the HLA system is revealed, to reduce the adhesive and proliferative properties of cellular elements.

The clinical period of primary tuberculosis infection takes 6-12 months from the moment of infection with tuberculosis, at this time the risk of development of the disease is highest. Distinguish usually asymptomatic pre-inflammatory period - the time from the penetration of mycobacterium tuberculosis in the child's body before the emergence of a positive tuberculin reaction (averaging 6-8 weeks), as well as the turn of tuberculin reactions - the transition of a negative reaction to a positive one. In the future, the relationship between the micro- and macroorganism is determined by a variety of factors, the most significant is the state of the child's body.