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84 Cards in this Set
- Front
- Back
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Which organism causes tuberculosis?
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Mycobacterium tuberculosis causes TB. These acid-fast bacilli are obligate aerobes and facultative intracellular organisms.
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What percentage of HIV-positive persons worldwide harbour Mycobacterium tuberculosis bacteria?
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1/3
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What colour do acid-fast bacteria stain?
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Red
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Is M. tuberculosis aerobic or anaerobic?
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M. tuberculosis bacteria are obligate aerobic organisms, so it makes sense that they most commonly infect the lungs.
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What is mycolic acid?
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Mycolic acid is a very large fatty acid that forms the backbone of mycosides, which are important virulence factors for M. tuberculosis.
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What are mycosides?
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Mycosides are glycolipids composed of mycolic acid molecules bound to a carbohydrate molecules.
Mycosides such as cord factor, sulfatides, and Wax D are virulence factors for M. tuberculosis. |
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What is cord factor?
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Cord factor is a mycoside formed by the union of 2 mycolic acid molecules with the disaccharide trehalose.
The presence of cord factor causes M. tuberculosis to appear to grow in cords. Cord factor is a major virulence factor for M. tuberculosis. |
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What are sulfatides?
How do they add to M. tuberculosis virulence? |
Sulfatides are mycosides with sulfate groups attached to the carbohydrate (trehalose).
Sulfatides prevent phagosomes containing bacteria from fusing to the lysosomes that would degrade them, thus accounting for the factultative intracellular nature of early M. tuberculosis infection. |
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What is the name of the large fatty acid found in mycosides?
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Mycolic acid
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What is Wax D?
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...
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What is the disaccharide in cord factor and sulfatides?
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Trehalose
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What's the name of the glycolipid molecule present in M. tuberculosis virulence factors?
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These molecules, which are fusions of mycolic acid and carbohydrates, are called MYCOSIDES.
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What does PPD stand for?
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PPD stands for purified protein derivative. These antigenic protein particles are injected into a person's skin. If the body mounts a cell-mediated response against them it suggests that they have been previously infected with M. tuberculosis.
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What is the PPD test? Give two alternate names for the PDD test.
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The PPD test is the Mantoux test is the tuberculin test. They are the same. Purified protein derivative, or PPD, which consists antigenic protein particles, is injected intradermally. If the person's body mounts a cell-mediated immune response against the PPD it indicates that they have previously been infected with M. tuberculosis.
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What does the Mantoux test actually test?
How does it work? What's another name for the Mantoux test? |
The Mantoux test actually tests if a person has previously been infected with TB.
Purified protein derivative, or PPD, which consists of antigenic protein particles, is injected intradermally. If the person's body subsequently mounts a cell-mediated immune response against the PPD then it can be inferred that they have previously been infected with M. tuberculosis. |
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How long does it take for a type IV hypersensitivity reaction to occur after injecting PPD?
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48 hours
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What does a positive Mantoux test indicate?
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Excluding false positives, a positive Mantoux test indicates that the person has at some point been infected with M. tuberculosis. The person may thus have active TB, latent TB, or a previous TB infection that has been cured.
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What is the BCG vaccine?
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...
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What does BCG stand for?
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...
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For all persons infected with M. tuberculosis, what percentage go on to develop actual active TB?
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10% (5% primary, 5% reactivation)
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What are the chances that close contacts of someone with pulmonary tuberculosis will become infected with M. tuberculosis?
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About 30%
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How is M. tuberculosis transmitted?
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M. tuberculosis is usually transmitted via aerosolized droplet nuclei from the aersolized respiratory secretions of an adult with pulmonary tuberculosis. This adult will shower the air with these secretions when he coughs, sings, laughs, or talks.
The inspired droplets land in the areas of the lung that recieve the highest air flow: the middle and lower lung zones. A person must have active TB to be contagious. |
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What is primary progressive tuberculosis?
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...
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What is a granuloma?
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...
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What event precipitates reactivation or secondary tuberculosis?
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It is presumed that a temporary weakening of the immune system may precipitate reactivation.
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What is the risk of secondary (reactivation) tuberculosis in an infected individual?
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10% lifetime risk
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What is the most common site of reactivation (secondary) tuberculosis?
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Upper lobes of the lungs
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What is the most common extrapulmonary manifestation of tuberculosis?
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The most common extrapulmonary manifestation of tuberculosis is lymph node infection.
The cervical lymph nodes are usually involved. |
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What is scrofula?
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Scrofula is infection of lymph nodes with M. tuberculosis bacilli.
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What is the name given to infection of the lymph nodes by M. tuberculosis?
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Scrofula
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What does XDR-TB stand for?
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XDR-TB stands for extremely drug resistant tuberculosis. It can also stand for extensively drug-resistant TB, which is the same thing.
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What does MDR-TB stand for?
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MDR-TB stands for multi-drug resistant tuberculosis.
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What is the 5 year survival rate for untreated TB?
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Not good.
35-50% |
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What is caseous necrosis?
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Caseous necrosis is a form of cell death in which the tissue maintains a soft and white cheese-like appearance.
Frequently, caseous necrosis occurs in the centre of the granulomas formed in tuberculosis. |
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What are Type IV hypersensitivity reactions?
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Type IV hypersensitivity simply refers to the harmful aspects of cell-mediated immune responses.
Principle among these is excessive granuloma formation. Very numerous confluent granulomas can displace so much normal tissue that they interfere with normal function. |
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What are the principle cells recruited to the site of injection in a tuberculin/Mantoux/PPD test?
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Monocytes/macrophages and TH1 cells
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When and why do granulomas form?
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Granulomas form when cell-mediated immunity in the form of activated macrophages is unable kill intracellular pathogens in a timely fashion.
More macrophages and T lymphocytes are recruited and eventually arrive on the scene as a granuloma begins to form. The macrophages with their intracellular pathogens form the centre of the granuloma, with T cells building up around them, "walling off" the pathogens from the rest of the body. In the case of tuberculosis, granulomas begin to form because M. tuberculosis resists the killing mechanisms of macrophages, surviving within them. As more and more immune cells are recruited to the scene the lesion begins to form, building out from the centre. |
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What are granulomas?
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Granulomas are clusters of immune cells that develop when cell-mediated immunity is not able to finish of intracellular pathogens in a timely fashion.
Macrophages with intracellular pathogens form the centre of granulomas. Recruited T cells form the outer rings. The structure serves as a physical barrier to the spread of infection as the layers of immune cells have a "walling off" effect on the pathogens on the inside. The macrophages in the centre may coalesce to form epithelioid giant cells. In tuberculosis the granulomatous lesions that form as the immune system responds to M. tuberculosis are called tubercles. There are two fates possible for the material at the centre of the granuloma: On one hand, fibrosis and subsequent calcification may occur. On the other hand, the material may die (caseous necrosis) and liquefy, allowing the pathogens to leak out and spread. I don't think this last part is right. |
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What is a tubercle? What is the etymology of tubercle?
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In general, tubercle is a term used in biology to refer to a small rounded projection or protuberance.
In tuberculosis, the tubercles referred to are the granulomatous lesions that form as part of the immune response to M. tuberculosis. Tubercle comes from the Latin tuberculum, meaning small swelling, boil, or pimple. |
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Why is tuberculosis called tuberculosis?
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Tuberculosis is so-named because of the formation of tubercles, or granulomas, in patients infected with M. tuberculosis bacilli.
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Which part of the lung does primary TB occur in?
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Though primary TB may involve any lobe, it most commonly occurs in the lower or middle lobes.
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In what percentage of cases does primary TB infection result in clinical pneumonia?
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5%
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Describe the natural history of TB infection.
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1) Transmission (aersolized droplets reach lungs)
2) Primary TB -Asymptomatic (most cases) -Symptomatic (less frequent and mostly in the immunocompromised) -Symptomatic with primary progressive disease (uncontrolled primary disease with cavitation) 2) Latent TB -M. tuberculosis bacilli contained within granulomatous tubercles 3) Reactivation/secondary TB -bacilli break out of granulomas and spread within lungs or to lymph nodes, kidneys, bones, or the CNS -presents with chronic cough, low-grade fever, weight loss, and symptoms associated with other organ systems affected 4) Transmission to the next person |
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Describe the initial immune response to the arrival of M. tuberculosis in the lungs.
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M. tuberculosis is greeted, like all invaders that reach the alveoli, with phagocytosis by alveolar macrophages and a subsequent immune response involving PMNs followed by more macrophages.
M. tuberculosis bacilli, however, have virulence factors that allow them to avoid intracellular killing and survive inside macrophages |
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What are the two potential manifestations of primary tuberculosis infection?
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Primary tuberculosis infection can either be symptomatic or asymptomatic.
The majority of cases are asymptomatic. In these patients, cell-mediated defences kick in and the foci of bacteria become walled off in granulomas. The granulomas heal with fibrosis and calcification. The organisms in these lesions are decreased in number but remain viable. Symptomatic primary tuberculosis occurs far less frequently and only really in the immunocompromised (e.g. children, the elderly, and the HIV-positive). Even symptomatic primary TB will eventually be contained by cell-mediated immunity in most patients. A small portion of patients with symptomatic primary infection will develop progressive primary disease. This occurs when cell-mediated immunity cannot contain the infection and tissue damage occurs, leading to cavitation. |
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What is the name given to a calcified tubercle in the middle or lower lung zone?
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Ghon focus
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What is a Ghon focus?
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A Ghon focus is a calcified tubercle in the middle or lower lung zone.
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What is the name given to a Ghon focus accompanied by perihilar lymph node calcified granulomas?
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Ghon or Ranke complex
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What is a Ghon complex (also known as Ranke complex)?
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A Ghon or Ranke complex refers to a Ghon focus accompanied by perihilar lymph node calcified granulomas.
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What does primary progressive disease mean in the context of tuberculosis?
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Most cases of symptomatic primary TB will eventually be contained by the host's cell-mediated immune response, even if this response is somewhat weaker than in a normal person.
In some cases, however, the cell-mediated response does not contain the primary infection, and progressive consolidation and cavitation occur even in the course of the primary infection. Such cases are called "primary progressive disease." |
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Who first identified the bacteria responsible for tuberculosis?
What year did this happen in? |
Robert Koch (1882)
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About how long after initial infection does cellular immunity against M. tuberculosis develop?
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Cellular immunity develops around 2-10 weeks after the initial infection.
If primary symptomatic TB doesn't resolve after this point, primary progressive disease is present. |
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Describe the progression of a tubercle lesion from initial inflammation to calcification.
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Inflammation --> granuloma formation --> caseous necrosis --> liquefaction --> cavitation --> fibrosis --> contraction --> calcification
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Why do patients with advanced HIV have an atypical presentation of TB in which the organism is widely disseminated but there is little evidence of cavitation and fibrosis?
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Tissue damage in tuberculosis is caused by the cell-mediated immune response.
(Recall that damage caused by cell-mediated immunity is called type IV hypersensitivity) Much of the destruction that occurs during TB infection requires an intact cellular immune system. This is obviously lacking in patients with advanced HIV. This is a KEY concept. In tuberculosis it is the host's own immune system that causes the tissue damage. |
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What is directly responsible for the tissue damage seen in TB infection?
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The host's own cell-mediated immune system is what directly causes the tissue damage and cavitation.
This is why patients with advanced HIV have an atypical presentation of TB in which the organism is widely disseminated but there is little evidence of cavitation and fibrosis. |
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Where does TB typically reactivate? Why?
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Characteristic locations for reactivation tuberculosis are the apical regions of the upper lobes. These regions have high oxygen tension and relatively less perfusion and thus are believed to be particularly suitable for survival of the aerobic bacilli.
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Why was TB called "consumption"?
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Weight loss (cachexia) and loss of appetite (anorexia) are often features of active TB.
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What is the distinction made between tuberculous infection and tuberculous disease?
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Tuberculous infection is defined by a positive tuberculin skin test or a postive IFN-gamma release assay but no evidence of active disease. It is the consequence of primary exposure, by which the bacilli have become established in the patient; however, host defence mechanisms have prevented any clinically apparent disease.
Tuberculous disease (active TB, or just simply tuberculosis), on the other hand, is clinically apparent disease due to infection with M. tuberculosis. Tuberculous disease includes active symptoms or abnormal findings on chest radiograph |
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What are the symptoms of pulmonary tuberculosis?
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Systemic: fatigue, low-grade fever, night sweat, anorexia, and weight loss
Respiratory: chronic cough, hemoptysis, sputum production |
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What is the objective of anti-TB therapy?
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The objective of anti-TB therapy is twofold: to achieve a lifetime cure of the disease while preventing drug resistance.
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What is INH?
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Isoniazid
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What is RMP?
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Rifampin
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What is PZA?
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Pyrazinamide
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What is EMB?
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Ethambutol
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How is drug resistance prevented in anti-TB therapy?
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Drug resistance is prevented when ALL mycobacterial populations are eliminated.
Total elimination does not allow for the emergence of resistant organisms. |
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What is sputum?
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Sputum is the mucus and other matter brought up from the lungs, bronchi, and trachea that one may cough up and spit out or swallow. The word "sputum" is borrowed directly from the Latin "to spit." Called also expectoration.
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What is expectoration?
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Expectoration is another word for sputum, or mucous brought up from the airways.
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For a person with latent TB (tuberculous infection), what is the risk of developing active TB?
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Without risk factors, TB develops in about 10% of infected, otherwise healthy adults in their lifetime, 5% within 2 years of infection and 5% after 2 years.
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What percentage of healthy adults with latent TB will develop active TB within 2 years of the initial infection?
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5%
Without risk factors, TB develops in about 10% of infected, otherwise healthy adults in their lifetime, 5% within 2 years of infection and 5% after 2 years. |
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What does LTBI stand for?
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LTBI stands for latent tuberculosis infection.
LTBI is synonymous with latent TB and tuberculous infection. |
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What does TST stand for?
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TST stands for tuberculin skin test. This test is referred to variably as the tuberculin skin test (TST), purified protein derivative (PPD) test, and the Mantoux test.
They are all the same. |
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Would you ever initiate LTBI treatment in a person with a negative TST (<5mm)? When and why?
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-HIV infection with high risk of TB infection (contact with infectious TB, from high incidence TB country, abnormal chest x ray)
-other severe immunosuppression with high risk of TB infection -child less than 5 with high risk of TB infection |
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What does BCG stand for?
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Bacillus Calmette-Guerin
The BCG vaccine is a somewhat-effective vaccine against tuberculosus. |
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Give a 2 potential reasons why a positive TST might be a false positive.
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People from other countries may have received the BCG vaccine and thus have immunologic memory for TB without ever having been infected.
Alternately, infection with other mycobacteria may result in false positives. |
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Give a potential reason why a negative TST might be false.
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A positve TST requires a robust cell-mediated immune response against the introduced antigen. Immunosuppressed patients (steroid use, malnutrition, AIDS, etc...) may lack this response and test negative even if they have been infected with M. tuberculosis.
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What's the name of the vaccine against tuberculosis?
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The tuberculosis vaccine is called the Bacillus Calmette-Guerin vaccine, or BCG vaccine.
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Who is R.G. Ferguson?
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...
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What does IGRA stand for?
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IGRA stands for interferon-gamma release assay.
This is a test used to diagnose tuberculosis. |
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What are the advantages of IGRA over tuberculin skin testing?
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IGRA has higher specificity than a a tuberulin skin test. Why? A TST may be falsely positive in those who have received the BCG vaccine.
None of the antigens used in the IGSA test are present in the BCG vaccine. Therefore the host cells will only release IFN-gamma if they have previously encountered the full M. tuberculosis bacteria. In short, IGRAs facilitate the differentiation of latent TB from prior vaccination with BCG. |
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How does the interferon-gamma release assay work?
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Lymphocytes from the patient's blood are incubated with the antigens. If the patient has been exposed to tuberculosis before, T lymphocytes produce interferon γ in response.
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When is a TST result of betweeen 5 and 10 mm considered positive?
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•HIV-infected persons
•Recent contacts of a person with infectious TB disease •Persons with fibrotic changes on chest radiograph consistent with prior TB •Organ transplant recipients •Persons who are immunosuppressed for other reasons (e.g., taking equivalent of ≥15 mg/day of prednisone for 1 month or more or those taking TNF-α antagonists) |
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In whom is a TST reaction >10 mm but less than 15 mm considered positive?
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•Recent immigrants (within last 5 years) from high-prevalence countries
•Injection drug users •Residents or employees of high-risk congregate settings (prisons, jails, long-term care facilities for the elderly, hospitals and other health care facilities, residential facilities for patients with AIDS, and homeless shelters) •Mycobacteriology laboratory personnel •Persons with clinical conditions previously mentioned •Children younger than 4 years of age •Infants, children, or adolescents exposed to adults at high risk for TB disease |
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How large must the TST reaction measure for the test to be considered positive in a person with no known risk factors for TB?
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>15 mm
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