The bacteria usually attack the lungs, but TB bacteria can attack any part of the body such as the kidney, spine, and brain. Not everyone infected with TB bacteria becomes sick. If not treated properly, TB disease can be fatal. Skip directly to site content Skip directly to page options Skip directly to A-Z link. Tuberculosis TB. Section Navigation. Facebook Twitter LinkedIn Syndicate. The classical view of the mycobacterial cell wall structure has been revised thanks to the introduction of a new electron microscopy technique, cryo-electron tomography on vitreous section, that preserves cell wall organization by avoiding sample dehydration.
The outer and inner membrane form a periplasmic space, with the presence of a thin layer of peptidoglycan in the innermost side covalently linked to arabinogalactan and lipoarabinomannan which in turn are bound to mycolic acids. Isoniazid and ethambutol, two of the most effective anti-TB drugs, target the synthesis of the mycolic acids and arabinogalactan, respectively, highlighting the importance of the mycobacterial cell wall in Mtb biology.
Protein secretion systems are the main virulence factors of pathogenic bacteria and in Mtb five type 7 secretion systems were identified ESX Figure 1. ESX3 is involved in the acquisition of iron and zinc by Mtb and is essential for growth also in culture. ESX1 and ESX5 secrete different proteins involved in the virulence of Mtb: ESX1 secretes antigens that interfere with the integrity of the phagosomal membrane, leading to phagosomal rupture and bacterial emission into the cytosol.
ESX5 is present only in slow growing mycobacteria such as Mtb and M. ESX3 is involved in Zinc and Iron uptake and homeostasis and as such is essential for growth. Another group of proteins known to play an important role in pathogenesis are those under the control of the dormancy survival regulon Dos , which controls expression of more than 50 genes responsible for the Mtb hypoxic response.
Mtb infection occurs when few tubercle bacilli dispersed in the air from a patient with active pulmonary TB reach the alveoli of the host. Here, Mtb is quickly phagocytized by professional alveolar macrophages that most often can kill the entering bacteria thanks to the innate immune response Figure 2.
In this scenario, when, during latent infection, for unknown reasons, bacilli would start replicating inside this primary lesion, active disease would ensue. This hypothesis was challenged since the early 20 th century, when it was shown that viable and infective bacilli were found in unaffected portion of lung tissues of infected guinea pigs or human necropsy rather than from the central core of the tuberculous lesions.
Using similar experimental settings, Mtb was detected in the fat tissue surrounding several organs, residing intracellularly in adipocytes, where it can survive protected from the host immune response.
Tubercle bacilli are inhaled in aerosol droplets, enter into the lungs and, when the host innate immune defenses fail to eliminate the bacteria, Mtb start multiplying inside alveolar macrophages and then spreads to other tissues and organs through the bloodstream and lymphatics. During latent infection a dynamic equilibrium between the bacilli and host immune responses is established and any event that weakens cell mediated immunity may lead to active bacterial replication, tissue damage and disease occurs active TB.
Studies carried out in the non-human primate model of TB further corroborated these findings indicating that during latent infection Mtb is metabolically active and replicates in host tissues despite the lack of any clinical sign or symptom of disease. Based on the new understanding of the biology of Mtb , its different metabolic states, the dynamic host immune responses occurring during infection and on the spectrum of conditions that are observed during infection, it has been proposed that during latent infection most bacilli persist in a dormant state with fewer Mtb found in an active replicating state.
When, for any reason, host immune responses fail to control these scouts, uncontrolled bacterial replication promotes diseases manifestations and active disease ensues. Cancer patients, including those with haematological diseases, are also at increased risk of developing TB and in these patients clinical outcomes are usually very aggressive, may present as systemic infections with a high fatality rate and diagnosis is usually delayed.
Hence, it is very important to deploy proper and effective diagnostic protocols capable of detecting latent infection in these high risk groups and very sensitive assays to identify active disease when TB is suspected. Definitive diagnosis of TB requires the detection of Mtb from the biological sample by at least one of the current microbiological techniques: microscopical analysis, isolation in culture or molecular methods.
These assays form the basis for the microbiological diagnosis of TB and the clinicians may require detection of Mtb in one or more specimens depending on the clinical symptoms, if any. Detection of Mtb in the urine or stools could be used to detect systemic infections and recently new assays capable of detecting mycobacterial components lipoarabinomannan, LAM in the urine were shown to be helpful to diagnose TB in HIV-infected subjects and immunocompromised patients, but not to diagnose pulmonary TB in immunocompetent subjects.
The immunological diagnosis of TB has been historically performed by the Mantoux test or tuberculin skin test TST and the introduction in the last decade of the interferon-gamma release assays IGRAs , that measure T cell responses directed against Mtb specific antigens in peripheral whole blood, has provided a new and valuable tool in the diagnosis of Mtb infection. The concept of the TB spectrum discussed in this review provides the biological and immunological framework to support this statement.
Competing interests: The authorshave declared that no competing interests exist. National Center for Biotechnology Information , U.
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Author information Article notes Copyright and License information Disclaimer. Correspondence to: Prof. Largo A. Gemelli, 8 — — Roma. Received Oct 28; Accepted Nov Copyright notice. This article has been cited by other articles in PMC. Abstract Tuberculosis TB still poses a major threat to mankind and during the last thirty years we have seen a recrudescence of the disease even in countries where TB was thought to be conquered. Introduction Tuberculosis TB is one of the ancient and deadliest disease of mankind, still posing a major health, social and economic burden at a global level and primarily in low and middle income countries.
The Bacillus Mtb is a slow growing mycobacteria with a doubling time of 12—24 h under optimal conditions. Open in a separate window. Figure 1. TB Pathogenesis Mtb infection occurs when few tubercle bacilli dispersed in the air from a patient with active pulmonary TB reach the alveoli of the host.
Figure 2. TB pathogenesis Tubercle bacilli are inhaled in aerosol droplets, enter into the lungs and, when the host innate immune defenses fail to eliminate the bacteria, Mtb start multiplying inside alveolar macrophages and then spreads to other tissues and organs through the bloodstream and lymphatics. TB Diagnosis Direct diagnosis Definitive diagnosis of TB requires the detection of Mtb from the biological sample by at least one of the current microbiological techniques: microscopical analysis, isolation in culture or molecular methods.
Immunological Diagnosis The immunological diagnosis of TB has been historically performed by the Mantoux test or tuberculin skin test TST and the introduction in the last decade of the interferon-gamma release assays IGRAs , that measure T cell responses directed against Mtb specific antigens in peripheral whole blood, has provided a new and valuable tool in the diagnosis of Mtb infection.
Footnotes Competing interests: The authorshave declared that no competing interests exist. A rare form of transmission is the ingestion swallowing of unpasteurized milk from an infected animal — in this case the person becomes infected with Mycobacterium bovis , the animal form of the TB bacterium. This way of infection plays a role in rural places, where people drink milk straight from the cow.
To avoid this, milk should always be boiled before drinking — this way the bacteria and germs are killed. The milk that can be bought in supermarkets is usually already pasteurized. Usually TB cannot be transmitted from a pregnant mother to her baby, because it does not cross the placenta.
A rare exception is miliary TB, when the TB bacilli might break through the placenta to the fetus. However, babies can get infected during birth, if the instruments used are infected: for example, if a baby needs a mask to help her breathing, and this mask contains TB bacilli. TB recognizes no difference between color, race, social status or gender and anyone may become infected.
However, there are risk factors that make certain people more vulnerable to developing active TB after inhaling the TB bacillus. The strength of the immune system determines whether or not a person who gets infected with the TB bacillus will be able to fight the bacillus and keep it in check, or develop active TB.
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