Introduction to TB
What is TB?
Tuberculosis is caused by an infection with Mycobacterium tuberculosis, rod-shaped bacteria that are spread mostly through air-born droplets or dust microparticles of dried sputum. Once inhaled, the body's immune system typically reacts by engulfing the bacteria, forming a tubercle that contains the bacteria to help keep it from spreading. In most cases, the bacteria will die; in others, however, the bacteria can survive, become dormant, and the infected individual may develop active disease at a later date, sometimes soon after infection, sometimes years later.
Those who develop active pulmonary tuberculosis experience a range of signs and symptoms, including chest pain, cough, weight loss, pallor, fever, and night sweats. People with suppressed immune systems, such as persons with HIV and AIDS, are much more likely to develop active tuberculosis.
Only those with active TB are able to spread it, by coughing or sneezing. These actions release the bacteria from the lungs into the air, where it can be inhaled by others. The bacteria are able to survive in the air for several hours, but are weakened by direct sunlight.
Animals and humans are also affected by other related bacteria in the Mycobacterium tuberculosis complex, such as Mycobacterium bovis. The bacteria infect cows, buffalo, deer, and elk, among others. It can be transmitted to humans through unpasteurized milk and cheeses. The recognition of this led many governments to regulate dairy herds and the pasteurization of milk in the early twentieth century.
TYPES OF TB
Although Mycobacterium tuberculosis or bovis are typically inhaled or ingested, once in the body the bacteria are able to migrate to different areas if they are left untreated. Their location affects the signs and symptoms of the disease.
Click on one of the following types of TB to find out how it affects the body.
When tuberculosis attacks the adrenal glands they become inefficient at producing hormones, such as cortisol, causing adrenal insufficiency. Symptoms include weakness, muscle fatigue, weight loss, nausea and vomiting. When Dr. Thomas Addison first diagnosed adrenal insufficiency, in 1849, tuberculosis was the cause of 70-90% of the cases. Today TB accounts for 20% of the cases of adrenal insufficiency in developed countries. e.g. Addison's Disease
Central Nervous System
When the meninges, the membranes that surround the central nervous system (i.e. spinal cord, brain), are infected they become inflamed, which can affect brain and motor function. Fever and headache are the most common signs and symptoms. This tubercular infection is usually fatal and affects children more frequently than adults. e.g. Tuberculous meningitis
If the tuberculous bacteria spread to the heart, they most commonly affect the pericardium, the sac that contains the heart and part of the major blood vessels. The presence and growth of the tubercles can cause fibrosis, and a hardening of the pericardium, which can restrict the action of the heart. e.g. Tuberculous pericarditis
Tuberculosis of the genitor-urinary system can manifest in a variety of symptoms depending on the location of the infection and its severity. Infection can produce fibrosis, which in turn can cause ureter stricture and other blockages. It can also cause infertility, genital ulcers, and kidney malfunction.
Representing approximately 75% of all tuberculosis cases, pulmonary TB is the most common form of the disease. Although the body forms a tubercle around the invading bacteria, they can continue to replicate inside, causing the tubercle to grow. As it gets larger, it may invade different parts of the lung, affecting the ability to breathe, or entering blood supply lines. Eventually the tubercle may grow so large that it bursts, spreading the bacteria that were inside.
When the lymph nodes are infected, in the neck or elsewhere in the body, they swell. Other symptoms may include fever and sweating. e.g. Scrofula
When TB affects the joints or the spine, it causes a softening of the bones. As the bones soften, they can compress. In the spine this may cause a hunchback, while in the joints this can present with arthritis-like symptoms. e.g. Pott's disease
When tuberculosis affects the skin it presents as lesions and growths that can persist for years and often leave scarring. e.g. Lupus vulgaris
Whether caused by the ingestion of tainted food products, or by swallowing infected sputum from the lungs, TB in the digestive tract produces ulcer-like lesions. Signs and symptoms include abdominal pain, diarrhea, and blood in the stool.
Miliary tuberculosis refers to a tuberculosis infection that has spread to multiple locations in the body through the blood stream or lymph system. It is characterized by the presence of multiple, small seed-like collections of bacilli, rather than larger granulomas.
HOW IT WORKS: cycle of bacterial infection
The bacteria are inhaled. The majority of the bacteria will become lodged in the upper respiratory tract, namely the nose and throat, where their survival is difficult. Some of the smaller particles, though, will make it into the lungs and alveoli where infection sets in. Alternatively, the bacteria might be ingested, for example through infected milk products.
2. Bacteria multiplication
In the alveoli, the bacteria are engulfed by unactivated macrophages - white blood cells present within tissues - where they multiply until the macrophage bursts. The Mycobacterium tuberculosis replicates very slowly, only once every twenty four hours, and takes up to one month to form a colony; in comparison, the E. coli bacteria form a colony in only eight hours.
3. T-cell activation
Dendritic cells are a key part of the mammalian immune system. They are present in our bodies where our tissues are in contact with the external environment, such as the skin and the lung alveolae. When dendritic cells detect foreign substances entering the body, they engulf them, process them into small molecular fragments (potential antigens) and bring them to the lymph nodes where they present the antigens to certain white blood cells called T-cells. If the T cell has a specific receptor for the presented antigen it will become activated to release potent molecules, such as interferon-gamma and tumour necrosis factor, which in turn stimulate macrophages and other T cells to produce a cell-mediated response against the bacteria carrying those antigens. Because it takes 48-72 hours to produce a cell-mediated response in the skin of an already sensitized individual, this reaction is called "delayed hypersensitivity."
4. Tubercle Formation
The T-cells return to the site of infection through the blood stream, where they contribute to the formation of a tubercle, or granuloma. The TB tubercle is made up of a core of infected macrophages, a surrounding ring of foamy macrophages (so named because the macrophages have ingested LDL cholesterol, causing them to appear foamy), and an outside ring of T-cells, all enveloped in a fibrous shell.
In some cases, an individual's immune system is unable to defend against the bacteria by creating a tubercle to isolate it. Primary progressive tuberculosis occurs as a result. This is mostly seen in young children or individuals with very suppressed immune systems.
When contained inside the granuloma the bacteria are inactive and the case of tuberculosis is considered to be latent. The bacteria are contained in the granuloma until the immune system is weakened, breaking down the outer ring of the tubercle, releasing the bacteria inside. In this situation, the case of tuberculosis has been reactivated and is known as secondary progressive tuberculosis. Only approximately 3-5% of immuno-competent individuals will develop secondary progressive tuberculosis within two years of the primary infection, and a further 3-5% will develop it after two years.
5. Cavitation and Tubercle break-down
In some cases, the damaged cells at the centre of the granuloma liquefy. The bacteria grow well in this liquid, multiplying outside of macrophages, their typical hosts. As they multiply, the tubercle enlarges. This can cause nearby tissue in the lungs to die and rupture, forming a cavity, or the tubercle to burst spreading bacteria further around the lungs or the body. This would also be considered a case of secondary progressive tuberculosis. The immune system will respond as per steps 3 & 4 when the bacteria are recognized in their new locations.