What causes tuberculosis?

The causative agent of tuberculosis is Mycobacterium tuberculosis. Although "consumption" as a disease was known in ancient times, there was a long and persistent struggle of opinions among various scientists on the etiology of the disease before the causative agent of tuberculosis was discovered. The infectious nature of tuberculosis was experimentally proven long before the causative agent of the disease was discovered. In 1865, the French scientist Villemin infected rabbits with tuberculosis by subcutaneously injecting them with tissues of affected organs and by inhaling sprayed sputum from tuberculosis patients.

In 1882, Robert Koch managed to detect a bacillus in tuberculosis foci when staining the preparation with methylene blue and obtain a pure culture of the pathogen. Scientists have established that mycobacteria tuberculosis have high resistance to the effects of any physical, chemical and biological agents. Having found themselves in conditions favorable for their development, mycobacteria tuberculosis can maintain viability and virulence for a long time. They tolerate prolonged cooling and drying. In dry form, at low temperatures, in the dark, in sewage water, mycobacteria tuberculosis live for about 300 days. In corpses, they remain alive for up to 160 days, and under the influence of sunlight they die in just 6-8 hours. According to Yu.K. According to Weisfeiler, the tuberculosis mycobacterium reproduces 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 a cavern (the most active tuberculosis focus), this author discovered reproduction by simple transverse division. In the process of development, tuberculosis mycobacteria can change their morphological properties under the influence of the environment.

Based on modern data, a whole doctrine about the tuberculosis pathogen has been created, which has significantly expanded and in many ways changed the understanding of its role in the pathogenesis of the disease. The tuberculosis pathogen (according to modern classification) belongs to the order Actinomycetales, family Mycobacteriaceсae, genus Mycobacterium. The existence of various morphological forms of the tuberculosis mycobacterium and a large range of variability of their biological properties have been noted.

Based on differences in biological properties, especially pathogenicity for humans and different animal species, four types of tuberculosis pathogens have been differentiated:

• M. tuberculosis, M. bovis - highly pathogenic for humans;
• M. avium causes diseases in birds and white mice;
• M. microti (Oxford vole strain) is the causative agent of tuberculosis in field mice.

M. tuberculosis and M. bovis can cause disease in both humans and many species of animals: cattle, goats, sheep, horses, cats, dogs, etc. These mycobacteria have a feature: sick animals can infect humans, and vice versa. Tuberculosis of the respiratory organs in children is most often caused by the M. tuberculosis species. Infection of children with bovine mycobacteria occurs mainly when consuming raw milk from sick animals.

The disease develops as a result of complex interaction of microbial factor and macroorganism in certain social and environmental conditions. Social factors are especially important in the development of tuberculosis. Under certain conditions, the causative agent of tuberculosis penetrates the child's body in various ways. The entry points of infection are most often the oral mucosa, tonsils, and less often other organs. Accordingly, the primary focus of inflammation has different localizations. Intrauterine infection with tuberculosis is also possible with specific damage to the placenta against the background of widespread tuberculosis in pregnant women or at the time of childbirth when swallowing infected amniotic fluid. The skin is the organ most difficult to infect with tuberculosis. Mycobacteria can penetrate the lymphatic pathways only through damaged areas of the skin. Such cases of infection have been described in medical workers during autopsies of people who died from tuberculosis. Mycobacterium infection is possible when using poorly sterilized instruments (inoculated primary tuberculosis). In 1955, R. Radanov studied the health of 11 such children in Plovdiv (Bulgaria) after intramuscular administration of benzylpenicillin using poorly sterilized reusable syringes that had previously been used to administer the anti-tuberculosis vaccine. In 1985, 21 newborns in the Orenburg maternity hospital were infected with tuberculosis when immunoglobulin was administered with syringes that had been used to inject a child with congenital tuberculosis. In most children, 3-4 weeks after the administration of the drug, an infiltrate with damage to the regional inguinal lymph nodes developed at the injection site on the buttock, similar to a typical primary tuberculosis complex. Some children experienced lymphohematogenous dissemination, leading to the development of miliary tuberculosis.

Primary infection is most often accompanied by the development of a focus in the intrathoracic lymph nodes and lungs. Mycobacteria cause the development of a necrotic focus, around which an inflammatory process appears: migration of leukocytes, accumulation of epithelioid cells, giant Pirogov-Langhans cells and lymphocytes. Thus, an epithelioid tubercle with a necrotic center is formed. A zone of nonspecific inflammation appears along the periphery of this specific area. The reverse development of a tuberculous tubercle can be accompanied by complete resorption, but fibrous transformation and calcification often occur. Such an outcome is not considered complete healing, since calcifications often contain live mycobacteria of tuberculosis. Under unfavorable conditions, especially in cases of uneven calcification, the focus can become a source of exacerbation of the disease. Non-specific or para-specific tissue processes are characterized by diffuse and nodular macrophage reaction, histiocytic-lymphocytic infiltration, non-specific vasculitis, fibrinoid necrosis, developing in the lungs, lymph nodes, heart, kidneys, liver, endocrine glands, synovial membranes, nervous system and leading to the development of sclerosis.

Already in the early stages of primary tuberculosis, the neuroendocrine system suffers, which leads to profound functional shifts that aggravate the disorganization of the body's physiological processes. The occurrence of secondary (after primary) tuberculosis is possible both as a result of superinfection (exogenous route) and as a result of reactivation of old foci - the remnants of primary tuberculosis (endogenous route). The question of the endogenous and exogenous route of spread of secondary tuberculosis cannot be resolved unambiguously. In some cases, both routes have a certain significance in the occurrence of the disease. With repeated exogenous infection, conditions are created for exacerbation and progression of the tuberculosis process. 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:

• the lesion in the organ - the primary lesion;
• tuberculous inflammation of the draining lymphatic vessels - lymphangitis;
• tuberculous inflammation of regional lymph nodes - lymphadenitis.

In case of airborne infection in the lungs, the primary tuberculosis focus (affect) occurs subpleurally in the best aerated segments, most often the right lung - III, VIII, IX, X (especially often in segment III). It is represented by a focus of exudative inflammation, and the exudate quickly undergoes necrosis. A focus of caseous pneumonia is formed, surrounded by a zone of perifocal inflammation. The size of the affect varies: sometimes it is alveolitis, barely visible microscopically, but more often the inflammation covers an acinus or a lobule, less often a segment, and in very rare cases the entire lobe. Involvement of the pleura in the inflammatory process with the development of fibrinous or serous-fibrinous pleurisy is constantly detected.

Very quickly, the specific inflammatory process spreads to the lymphatic vessels adjacent to the primary focus - tuberculous lymphangitis develops. It is represented by lymphostasis and the formation of tuberculous tubercles in the perivascular edematous tissue along the lymphatic vessels. A path is formed 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 cecum, tuberculous tubercles with necrosis and subsequent formation of an ulcer in the mucous membrane are formed, considered as the primary affect. Then tuberculous lymphangitis occurs with the appearance of tubercles along the lymphatic vessels and caseous lymphadenitis of the regional lymph nodes to the primary affect.

There are three possible courses 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 ongoing primary tuberculosis).

Theoretical and methodological advances in immunology have enabled researchers to characterize systemic and local changes in immunological reactivity in the tuberculosis process quite fully. Primary tuberculosis infection causes immunological restructuring - the body becomes sensitive to tuberculin, and delayed-type tuberculin hypersensitivity develops. 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 encounter between mycobacteria tuberculosis and a macroorganism depends on the massiveness of the infection, the virulence of the infection, as well as the state of the immune system of the organism, its natural resistance. In most cases, during primary infection, the growth of mycobacteria is inhibited and they are destroyed. Mycobacterium tuberculosis is a facultative intracellular parasite; in the body, it is mainly located in the phagosome of macrophages. The complexity of the antigenic structure of mycobacteria (over 100 antigenic structures have been identified) and the change in its composition throughout the life cycle allow mycobacteria to effectively adapt to coexistence with the cells of the immune system of the host organism, to a long stay in the organism with a change in the phases of extra- and intracellular parasitism. Mycobacteria not only adapt to coexistence with the cells of the immune system, but also have a negative effect on it. It has been established that tuberculosis mycobacteria synthesize an enzyme that inhibits the fusion of phagosomes with lysosomes. The ability of mycobacteria to reduce the expression of antigens of the 1st and 2nd classes of the HLA system, to reduce the adhesive and proliferative properties of cellular elements has been revealed.

The clinical period of primary tuberculosis infection lasts 6-12 months from the moment of contracting tuberculosis, during which time the risk of developing the disease is highest. A distinction is usually made between an asymptomatic pre-allergic period - the time from the penetration of tuberculosis mycobacteria into the child's body until the appearance of a positive tuberculin reaction (6-8 weeks on average), as well as a turn in tuberculin reactions - the transition of a negative reaction to a positive one. Subsequently, the relationship between the micro- and macroorganism is determined by many factors, the most significant of which is the state of the child's body.