**1. Introduction**

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Pharmacology 2010; 66 749–754.

126 Tuberculosis - Current Issues in Diagnosis and Management

#### **1.1. Inflammatory process of tuberculosis**

When many infectious units of 1-3 bacilli are inhaled, a phenotypically hardy bacillus is likely to be among them. In addition, the alveolar macrophages apparently vary in their capacity to destroy bacilli [1]. Staining for acid-fast bacilli is very useful for demonstrating *M. tuberculo‐ sis* (A). Fig. 1 reveals histologic manifestation of tuberculosis over the time course. Histologi‐ cally, tuberculosis displays exudative inflammation (B), proliferative inflammation (D) and productive inflammation (C) depending on the time course. Using animal experiments and an inhalation exposure system, the pathologic condition of the infected animals was followed up for one year. Exudative inflammation was observed for the first 10 days. Thereafter, granulo‐ mas, which corresponded to foci of proliferative inflammation, were formed. Cavity formation was not recognized in animal tuberculosis, except for rabbits. Using rabbit models, Dr. Arthur Dannenberg described the pathology of tuberculosis in detail [2, 3]. There are five stages: onset, symbiosis, early stages of caseous necrosis, interplay of cell-mediated immunity and tissue damaging delayed-type hypersensitivity, and liquefaction and cavity formation. In stage 1, tubercle bacilli are usually destroyed or inhibited by the mature resident alveolar macrophages that ingest them. If bacilli are not destroyed, they grow and eventually destroy the alveolar macrophages. In stage 2, bacilli grow logarithmically within the immature nonactivated macrophages. These macrophages enter a tubercle from the bloodstream. This stage is termed symbiosis because bacilli multiply locally without apparent damage to the host, and macro‐ phages accumulate and divide. In stage 3, the stage at which caseous necrosis first occurs, the number of viable bacilli becomes stationary because their growth is inhibited by the immune response to tuberculin-like antigens released from bacilli. Stage 4 is the stage that usually determines whether the disease becomes clinically apparent. Cell-mediated immunity plays a major role in this situation. The cytotoxic delayed- type hypersensitivity immune response

© 2013 Shi and Sugawara; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

kills these macrophages, causing enlargement of the caseous center and progression of the disease. If good cell-mediated immunity develops, a mantle of highly activated macrophages surrounds the caseous necrosis. In stage 5, bacilli evade host defenses. When liquefaction of the caseous center occurs, the bacilli multiply extracellularly, frequently attaining very large numbers. The high local concentration of tuberculin-like products derived from these bacilli causes a tissue-damaging delayed-type hypersensitivity response that erodes the bronchial wall, forming a cavity.

exposed to *M. tb*. Fig. 2 shows typical chest X-ray before (A) and after (B) chemotherapy. Fatigue, malaise, weight loss, low-grade fever, night sweats, cough, sputum, are the main symptoms. The sputum may also be streaked with blood. Hemoptysis can be due to destruc‐ tion of a patent vessel located in the wall of the cavity [7]. Extrapulmonary disease occurs in more than 20% of patients. The most serious location is the central nervous system, where infection may result in meningitis, which could be fatal in most cases. Another fatal form is infection of the blood stream by mycobacteria, this form is called disseminated or military tuberculosis. The most common extrapulmonary tuberculosis is lymphatic tuberculosis. Other

Pathophysiology of Tuberculosis http://dx.doi.org/10.5772/54961 129

**Figure 2.** Chest X‐ray of pulmonary tuberculosis and cured Tuberculosis A. before chemotherapy with rifampicin, iso‐

In human, a TB index case may infect a contact person through cough and expectoration, so the lung is the primary route of infection and often the main tissue exhibiting TB. Infec‐ tious droplet nuclei are deposited in the alveolar spaces of the contact person where *Myco‐ bacterium tuberculosis (M. tb)* can be phagocytosed by alveolar macrophages, epithelial cells, dendritic cells (DC) and neutrophils [8, 9]. Alveolar macrophages and DC are then believed to transport *M. tb* to local lymph nodes where T cell activation occurs and expand. Activa‐ tion of the phagocytic host cell is much required to limit growth of *M. tb*; as in the absence of activation, disease outcome is extremely poor. Effective phagocyte activation requires a specific cellular response, as infected hosts lacking specific components of the acquired re‐ sponse have a poor outcome [10]. While acquired cellular protection is expressed rapidly

niazide, ethambutol and pyrazinamide, B. after chemotherapy. Apical shadow (dotted circle) disappears.

**3. T cell activation against** *Mycobacterium tuberculosis*

possible locations include bones, joints, pleura, and genitourinary system [4].

A B

**Figure 1.** Histologic appearance of tuberculosis A. Staining for acid‐fast bacilli, B. exudative stage, C. productive stage with cavity formation (→), D. proliferative stage with a multinucleated giant cell.
