Tuberculosis: Videos & Practice Problems

Tuberculosis (TB), caused by the slow-growing, acid-fast Mycobacterium tuberculosis with a mycolic acid-rich cell wall and toxic cord factor, primarily infects the lungs via airborne transmission. The disease progresses through primary infection, latent infection with granuloma (tubercle) formation, and active infection, which is contagious and marked by symptoms like coughing blood. Diagnosis involves the Mantoux tuberculin skin test and chest X-rays showing Ghon complexes. Treatment requires intensive multi-drug regimens due to drug-resistant strains. The BCG vaccine offers variable protection, mainly in children, and TB’s pathogenesis highlights the immune system’s role in containment and disease progression.

Tuberculosis

Tuberculosis (TB) is a significant infectious disease primarily affecting the lower respiratory tract, caused by the bacterium Mycobacterium tuberculosis. These bacteria are characterized by their rod shape and unique cell wall containing mycolic acid, a waxy substance that makes them acid-fast and resistant to many common staining techniques. This mycolic acid-rich outer layer not only contributes to their slow growth but also plays a crucial role in their pathogenicity.

A key component of the M. tuberculosis cell wall is the cord factor, a glycolipid containing mycolic acid. Cord factor causes the bacteria to stick together in rope-like structures, which is visually distinctive under a microscope. More importantly, cord factor is toxic to mammalian cells and inhibits immune responses, particularly by suppressing neutrophil activity. This immune evasion mechanism contributes to the bacteria’s ability to persist in the host.

Transmission of tuberculosis occurs through respiratory droplets, making it a contagious airborne disease. While the lungs are the primary site of infection, M. tuberculosis can disseminate to other tissues, although initial infections outside the lungs are rare. Many individuals harbor the bacteria in a latent state, where the immune system contains the infection within granulomas called tubercles. These tubercles wall off the bacteria, preventing spread and symptoms, resulting in a latent TB infection that is non-contagious and asymptomatic.

When latent TB progresses to active disease, symptoms become apparent and include persistent cough, chest pain, difficulty breathing, and hemoptysis (coughing up blood). Historically, tuberculosis was known as "consumption" due to the severe wasting it caused in affected individuals.

Diagnosis of tuberculosis often involves the Mantoux tuberculin skin test, where purified protein derivative (PPD) is injected intradermally. A positive reaction indicates prior exposure or immune sensitization to TB antigens but does not distinguish between latent and active infection. Chest X-rays are also used to detect characteristic signs such as Ghon complexes, which represent calcified granulomas and lymph node involvement indicative of latent infection. Active TB may show more extensive lung damage on imaging.

Treatment of tuberculosis is challenging due to the bacteria’s slow growth, protective mycolic acid cell wall, and the presence of cord factor. Effective therapy requires prolonged, multi-drug regimens, typically including isoniazid and rifampin. However, the emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains complicates treatment, as these strains resist first-line antibiotics and are difficult to eradicate.

Immunity against tuberculosis can be partially conferred by the Bacillus Calmette-Guérin (BCG) vaccine, which is primarily administered in regions with high TB prevalence. The BCG vaccine offers strong protection against severe forms of TB in children but provides variable and often limited protection in adults, and immunity wanes over time.

Understanding the pathogenesis, transmission, diagnosis, and treatment of tuberculosis is essential for managing this persistent global health threat. The interplay between the bacterium’s unique cell wall components, immune evasion strategies, and the host’s immune response shapes the clinical outcomes and informs public health strategies to control TB.

Tuberculosis Example 1

When undergoing a tuberculosis (TB) screening, such as the Mantoux tuberculin skin test (also known as the PPD test), a positive result is indicated by an induration measuring 12 millimeters or more after 48 hours. This positive reaction signifies that the immune system has responded to the purified protein derivative injected during the test, suggesting prior exposure to the tuberculosis bacteria. However, a positive test does not necessarily mean the individual is contagious.

A positive PPD test can indicate several possibilities. One is an active TB infection, where the bacteria are actively multiplying and the person is contagious. This scenario, however, is less common. More frequently, a positive result reflects a latent TB infection, where the bacteria are contained within granulomas or tubercles in the lungs, preventing active disease and contagion. In this latent state, the bacteria remain dormant, and the individual typically does not spread TB to others. Another cause of a positive test could be prior vaccination with the Bacillus Calmette-Guérin (BCG) vaccine, which stimulates an immune response to TB antigens. This vaccine is generally administered in regions with high TB prevalence and is uncommon in countries like the United States.

To further evaluate a positive PPD test, a chest X-ray is often performed. The physician looks for characteristic signs of TB infection, such as Ghon complexes. A Ghon complex consists of a calcified tubercle in the lung tissue combined with an associated calcified lymph node, indicating a healed or latent TB infection. In cases of active TB, the chest X-ray may reveal more extensive abnormalities, including infiltrates, cavitations, or fluid accumulation in the lungs, reflecting ongoing infection and inflammation.

Understanding the distinction between latent and active tuberculosis is crucial for appropriate management and preventing transmission. The PPD test serves as a valuable tool for detecting immune sensitization to TB, but it must be interpreted alongside clinical findings and diagnostic imaging to determine the individual's infectious status and need for treatment.

Which of the following is required for M. tuberculosis to be virulent?

• A. Ghon complexes.
• B. Presence of neuraminidase enzyme.
• C. Infection by a phage.
• D. Presence of cord factor.

Answer: (D)

Tuberculosis can be especially difficult to treat for which of the following reasons?


I. It is slow-growing. 
II. Multi-drug-resistant strains are becoming more common.
III. The presence of mycolic acid and cord factor in the cell wall.

• A. I & II.
• B. I & III.
• C. II & III.
• D. I, II, & III.

Answer: (D)

Tuberculosis Pathogenesis

Tuberculosis (TB) progresses through three distinct stages: the initial (or primary) infection, latent infection, and active infection. The disease begins when Mycobacterium tuberculosis bacteria are inhaled and reach the alveoli, the smallest air sacs deep within the lungs. Here, alveolar macrophages attempt to engulf and destroy the bacteria. In individuals with strong immune systems or low bacterial loads, this process may successfully eliminate the infection. However, due to the bacteria’s unique features—such as their mycolic acid-rich cell wall and cord factor—they can survive and reproduce inside macrophages, eventually killing these immune cells and escaping back into the alveoli.

When the immune system cannot fully eradicate the bacteria, it shifts strategy to containment rather than elimination. Macrophages infected with M. tuberculosis cluster together, forming a tightly packed structure called a granuloma. In tuberculosis, this granuloma is specifically known as a tubercle. The tubercle is encased in collagen fibers, creating a barrier that walls off the bacteria and prevents their spread. Inside this structure, infected macrophages die, leading to a characteristic caseous (cheese-like) necrosis visible upon dissection. Despite the presence of live bacteria within the tubercle, the infection remains latent, and the person typically exhibits no symptoms. This latent infection can persist for a lifetime without causing disease or contagion.

Occasionally, the tubercle ruptures, releasing bacteria back into the lung tissue. This event can overwhelm the immune system, leading to active tuberculosis infection. During this stage, bacteria multiply extensively, forming new tubercles and causing lung tissue damage. Symptoms such as persistent cough, fever, and hemoptysis (coughing up blood) emerge. The presence of blood in sputum indicates alveolar damage and raises the risk of bacteria entering the bloodstream, potentially spreading to other organs like the spleen and liver. Active TB is contagious, especially when the infected person coughs, facilitating transmission to others.

This progression from initial infection to latent and then active disease highlights the complex interplay between M. tuberculosis and the host immune response. The granuloma or tubercle serves as a critical immunological structure that contains but does not eliminate the bacteria, balancing between bacterial survival and host defense. Understanding this pathogenesis is essential for recognizing why many infected individuals remain asymptomatic carriers, while others develop active, contagious tuberculosis.

Tuberculosis Example 2

An active tuberculosis infection involves Mycobacterium tuberculosis bacteria actively reproducing, but not within a tubercle. Instead, these bacteria spread throughout the lungs and potentially other parts of the body, overwhelming the immune system. A tubercle is a structure formed by the immune system to wall off the bacteria, containing them and preventing their spread. In latent tuberculosis infection, the bacteria remain contained within the tubercle, where their reproduction is minimal or halted due to limited space and resources, allowing them to persist for decades without causing active disease.

In most individuals infected with Mycobacterium tuberculosis, the immune system successfully walls off the bacteria within tubercles, preventing the disease from progressing beyond the latent stage. These tubercles effectively contain the bacteria, often resulting in a lifelong latent infection without symptoms or active disease.

While tuberculosis primarily affects the lungs, it can infect other regions of the body, such as the lymph nodes, bones, or kidneys. Contrary to some beliefs, extrapulmonary tuberculosis is generally considered a serious infection. The spread of tuberculosis beyond the lungs often indicates a more severe disease state and can be life-threatening if not properly treated.

Mycobacterium tuberculosis bacteria have the ability to reproduce inside alveolar macrophages, the immune cells that typically engulf and destroy pathogens. This intracellular survival is facilitated by factors like the cord factor, which helps the bacteria resist destruction. The bacteria multiply within macrophages, eventually killing them and contributing to the formation of tubercles, which serve to contain the infection but also indicate the ongoing battle between the immune system and the pathogen.

The exact progression of tuberculosis can vary based on the individual. For individuals that progress to severe disease, which of the following orders the stages of a tuberculosis infection correctly as most commonly experienced?

• A. Active infection à latent infection à dormant infection.
• B. Initial infection à dormant infection à latent infection.
• C. Dormant infection à active infection à latent infection.
• D. Initial infection à latent infection à active infection.

Answer: (D)

Which of the following statements about tuberculosis tubercles is correct?

• A. Tubercles can occur anywhere in the body infected by M. tuberculosis bacteria.
• B. Tubercles are formed when M. tuberculosis are packed together and surrounded by fibrin.
• C. Tubercles typically isolate M. tuberculosis over the short term, while a more stable granuloma can form.
• D. The presence of a “cheese-like” texture inside a tubercle indicates that the M. tuberculosis bacteria are no longer alive or active

Answer: (A)

Here’s what students ask on this topic:

What is the pathogenesis of tuberculosis and how does the disease progress in the lungs?

Tuberculosis (TB) pathogenesis begins when Mycobacterium tuberculosis bacteria are inhaled into the alveoli of the lungs. Alveolar macrophages attempt to engulf and kill the bacteria, but due to the bacteria's protective mycolic acid cell wall and toxic cord factor, they often survive and reproduce inside these cells. This leads to a back-and-forth battle where macrophages are killed and replaced. The immune system then walls off the infected macrophages by forming a granuloma called a tubercle, which isolates the bacteria in a latent infection stage. The bacteria remain alive but contained, and the person is asymptomatic and non-contagious. If the tubercle ruptures, bacteria spread, causing active infection with symptoms like cough, chest pain, and blood in sputum. This active stage is contagious and can lead to systemic spread, affecting organs like the liver and spleen.

How is tuberculosis diagnosed and what are the key tests used?

Tuberculosis diagnosis primarily involves the Mantoux tuberculin skin test and chest X-rays. The Mantoux test injects purified protein derivative (PPD) into the skin to check for an immune response. A positive reaction indicates exposure to TB bacteria but does not distinguish between latent or active infection or vaccination. Chest X-rays help identify lung abnormalities; in latent TB, Ghon complexes—calcified granulomas and lymph nodes—may be visible. Active TB shows more extensive lung damage. These tests together help determine if a person has been infected and if the infection is active, guiding further treatment decisions.

What makes Mycobacterium tuberculosis difficult to treat and what challenges exist with drug resistance?

Mycobacterium tuberculosis is difficult to treat because it is slow-growing and has a waxy, mycolic acid-rich cell wall that protects it from many antibiotics and immune responses. Additionally, the toxic cord factor helps the bacteria evade immune cells like neutrophils. Treatment requires intensive multi-drug regimens over several months to effectively kill the bacteria. However, drug-resistant strains have emerged, including multi-drug resistant (MDR) strains resistant to first-line drugs like isoniazid and rifampin, and extensively drug-resistant (XDR) strains that are nearly untreatable. These resistant strains pose significant challenges for TB control and require alternative, often more toxic and expensive, treatment options.

What is the role and effectiveness of the BCG vaccine in tuberculosis prevention?

The Bacillus Calmette-Guérin (BCG) vaccine is used to prevent tuberculosis, especially in regions with high TB prevalence. It provides good protection against severe forms of TB in children, such as TB meningitis and miliary TB. However, its effectiveness in adults is variable and generally less reliable. The vaccine does not provide lifelong immunity and is not commonly used in countries with low TB incidence, like the United States. While BCG vaccination can reduce the overall spread of TB, it does not guarantee complete protection, so other public health measures and treatments remain essential.

What are the symptoms of active tuberculosis and how does it differ from latent TB infection?

Active tuberculosis presents with symptoms such as persistent cough, chest pain, difficulty breathing, and coughing up blood (hemoptysis). Patients may also experience fever, weight loss, and night sweats. In contrast, latent TB infection is asymptomatic; the bacteria are contained within granulomas (tubercles) in the lungs and do not cause illness or spread to others. Latent TB can persist for years without symptoms, but it can reactivate into active TB if the immune system weakens, leading to contagious disease and symptoms.