Immunological Aspects of Chest Diseases: The Case of Tuberculosis

Immunological Aspects of Chest Diseases: The Case of Tuberculosis

INTRODUCTION

The respiratory tract is one of the first portals of entry for many viral and bacterial microorganisms. The local defense systems are generally sufficient to handle most invading microorganisms in healthy individuals but if the lung is damaged by bronchiectasis or fibrosis, the infecting microorganisms are able to establish an infection, cross the epithelial layer, and cause invasive disease.

The respiratory tract has two main com-partments. The first is the airways, which extend from the nose to the terminal bron-chioli. The second area is the alveoli in the lung tissue. The airways’ defenses include many features such as ciliary movement, mucus, antimicrobial proteins, and rapid arrival of neutrophils whose combined action make it difficult for organisms to establish an infection. The access to the alve-oli is also generally limited to very small inhaled particles. In the alveoli, invading microorganisms encounter resident alveo-lar macrophages that play a major role in engulfing and killing invaders.

The lung has its own immune system, which is known as bronchus-associated lymphoid tissue. Antigen-specific immune responses are generated at these sites, which, similarly to the Peyer’s patches in the intestine, contain dendritic cells (DCs), which are the main antigen-presenting cells, as well as T and B cells, the latter

organized into B-cell follicles, as well as macrophages. Immune responses occur in response to infections or injury to the tract. The main antibodies found in respiratory tract secretions are IgA and IgG. However, B cells producing IgE and IgG are also found in the lung. Why IgE is present in this tissue is unclear but IgE may have a role in controlling parasites that reach the lung as it does in the intestines. IgE plays a major role in hypersensitivity reactions that occur in the respiratory tract, such as asthma and hay fever.

There are a variety of respiratory dis-eases including infectious diseases, inter-stitial lung disease, and allergic diseases. However, we will concentrate on tubercu-losis (TB), one of the most important global granulomatous diseases in the world today.

TB is arguably the single most success-ful pathogen humankind has ever known. The unparalleled penetrance of TB in the human population reflects the extraordi-nary ability of Mycobacterium tuberculosis to cause a lifelong persistent infection, a peculiarity that is likely the result of a long dynamic interaction with its host. Although microbial infections, including those caused by highly pathogenic bac-teria, tend to run an acute course, with infectious cycles of a few weeks, mycobac-terial infections such as leprosy and TB are unusually protracted due to these patho-gens’ proclivity to persist in their hosts.

Table 13.1 Genetic Immunodeficiency Syndromes that Predispose to Mycobacterial Infection

Persistence by M. tuberculosis can occur in the form of chronic active disease or latent infection; in either form, the biology of M. tuberculosis’ persistence is poorly understood. Because available antibiotics are inefficient in eradicating persistent bacteria, treatment must be extended, and often lasts between six and nine months. Despite the inherent difficulties in implementing these sorts of regimens, antibiot-ics have effectively reduced TB in most of the industrialized world. However, they have had less impact in the rest of the world, where lack of resources make implementing such cumbersome drug treatments considerably more difficult. Most people live in the developing world, and it is there – where poverty is extreme, public health deplorable, and malnutrition and overpopulation widespread – where TB relentlessly and inexorably continues to exact its deadly toll. Although it is clear that combating the current TB epidemic would be greatly facilitated by the devel-opment of new and more efficient drugs and vaccines, the major obstacle in deal-ing with TB and other major infectious diseases such as malaria and HIV is the uwillingness of the industrialized world to make the investments needed to facilitate the efficient distribution of already avail-able drugs, as well as the discovery of new ones.