2.3 Etiology and Immunity. The latent infection

The morphological and biochemical components of microbial cells cause various reactions in the host. The basic biochemical components of МВТ are proteins, carbohydrates and lipids. Protein (tuberculoproteid) is the basic carrier of antigenic properties МВТ.

Tuberculin – one of the tuberculoproteids, widely used in practice for revealing MBT infection.

Delayed-type hypersensitivity (DTH).
The substances, which are included in structure of MBT wall, induce tissue specific inflammation reaction and granuloma formation, with development of the delayed-type hypersensitivity (DTH), which could be detected by reaction on tuberculin test, and weak antibody formation. In general, term DTH is used for characteristics of a type IV immune response (induration at the site of intradermal injection of tuberculin develops after 48 hours) among individuals who infected with Mycobacterium tubercu¬losis. DTH is to be concerned as an immune response from the damaged tissue factors.

Relationship between the immune response and pathogenesis.

Local and general lesions causes by tuberculosis in the organism determine by the defensive responses, that the host’s immune system mounts against the bacilli in its tissues. In the description of this most complex process, we will limit ourselves to the simple enumeration of the events, proceeding from the moment of primary penetration of MBT into the alveoli, to the results of true battle between the macroorganism and the MBT. This process determines fate, at least, third of population of world, which is infected with mycobacterium tuberculosis. The cycle of the development of tuberculosis from the infection of organism by mycobacterium tuberculosis, clinical manifestations of disease and spreading of MBT, in the environment, can be conditionally divided into 5 stages. Each of these stages in turn consists of a large quantity of the events.

Stages.

1. Spreading of infection.
2. Beginning of infection, proliferation and dissemination in an infected host.
3. Formation of immune reaction of the host.
4. Formation of caseous necrosis, proliferation of bacteria.
5. Secoundory spreading of infection (ability to infect).

Brief description of each stage.

Stage 1. Spreading of infection.

1. Patient produce aerosol that contains MBT.
2. Smaller particles of aerosol dehydrate to form droplet nuclei.
3. Droplet nucleus containing mycobacterium is inhaled by man.
4. Droplet nucleus penetrate through bronchi and is deposited in alveolus.
5. Mycobacterium swallowed by the alveolar macrophages of the non immunized organism.
6. If alveolar macrophages are able to kill the MBT; Infection not occurs.

Stage 2. Beginning of infection, proliferation and dissemination.

1. MBT survive within alveolar macrophages and proliferate.
2. Proliferating MBT kills alveolar macrophages and destructed macrophages release chemokines, freed chemokines interact with the new cells.
3. New alveolar macrophages and monocytes catch and ingest MBT.
4. Killer cells, and T lymphocytes begin to appear in lesions.
5. MBT continue to proliferate, killing host cells and spreading locally.
6. MBT transported to intrathoracic lymph nodes and from there they spread systemically.

Stage 3. Formation of immune reaction of the host.
Formation of process of tuberculosis in the Stage 3 can occur in two variants.

Variant 1. Most patients who enter Stage III develop sufficient immunity to control the tuberculosis for lifetime.

1. MBT proliferation is halted and the bacillary population falls substantially.
2. The primary lesion and metastatic foci involutes, leaving minimal residuals.
3. The tuberculin skin test becomes reactive; it’s indicated the hidden, latent infection.

Variant 2. During insufficient immune response develops progressive tuberculosis process. This situation is often observed among the children, AIDS patients and also among others who have predisposition to the tuberculosis. However, some undergo REACTIVATION of latent infection: may occur at extrapulmonary site(s) or in lung. Reactivation of disease may end with tissue lesions, cavity formation and secondary MBT proliferation.

On the cell level Stage 3 characterizes by following processes.

1. Immune response of macro organism: macrophages submit tuberculosis antigens to T lymphocytes; T cells release cytokines.
2. Cytokines recruit and activate macrophages; results immune response includes protective cellu-lar and tissue-lesions.
3. These response limit proliferation and/or kill, MBT, resulting in involution of the primary lung lesion and the remote, extrapulmonary foci, or
4. If the host fails to mount effective response, progression of primary disease proceeds, localized in lung and/or extrapulmonary sites.

Stage 4. Caseation and accelerated bacillary proliferation

1. Pulmonary focus reactivates and undergoes necrosis (Caseation) with cavity formation.
2. MBT located in the extracellular space exponentially multiplie.

Stage 5. Retransmission of the infection.

1. Patient expectorates MBT in sputum; another person inhales them; epidemiological process of tuberculosis becomes completed.

Conclusion.
The complex of the contributing factors is necessary for development of clinical manifestations of tuberculosis. It is known, that frequently among healthy people virulent tuberculosis mycobacterium are found out, however not all of them being their carriers manifest clinical symptoms of tuberculosis. Only at presence of complex numerous adverse external and internal contributing factors, sharply lowering of a host resistance, tubercular infection can proceed in disease – tuberculosis. At the same time, the tubercular contamination can be ended by the so-called latent infection.

The latent infection.

As the latent infection it is accepted to consider such infectious process, at which there are no clinical displays of illness at presence viable mycobacteria in the host The existence of process at the latent infection can be established by means of pathomorphological examination or with the help immunobiological reactions. The tuberculosis latent infection is a consequence:

• of the undeveloped primary infection, at which MBT continue to remain in a host;
• of the unfinished process of the transferred tuberculosis in past.

The tuberculosis latent infection can develop in both situations. In any case MBT exist in a host, but conditions of the latent infection occurrence are different. In the first situation the latent infection arises at presence of some inherent of the host’s resistance, due to what the infectious focus does not develop. In second – it is a consequence of developed immunity during illness, when there is a latent focus. In both cases the reaction of the host is unsufficient to destroy MBT.

Hence, the occurrence of the tuberculosis latent infection depends both on a degree of MBT virulence, and from a condition of host’s tolerance and immunobiological reactivity. The influence of external environment has been also important.