In vitro Immunomodulation of a whole blood IFN gamma release assay enhances T cell responses in subjects with latent TB infection Flashcards

Question 1

Q

What is latent tuberculosis? Detail the host-pathogen interaction and why the organism becomes latent. Why is it important to diagnose latent tuberculosis?

Answer

A

A diagnosis of Latent tuberculosis means a patient is infected with Mycobacterium tuberculosis, but the patient does not have active tuberculosis disease. Active tuberculosis is contagious while latent tuberculosis is not. The main risk of having Latent TB is that a subset of patients will go on to develop active tuberculosis at a later stage of their life. This is particularly dangerous for individuals that are immunocompromised. It is therefore vitally important to be able to diagnose and treat Latent TB.

TB becomes latent when the immune system isn’t able to keep Mycobacterium tuberculosis in check. The presence of the bacteria causes an inflammatory response in which white blood cells are recruited to sites of infection. They form a walled off lesion, known as a “tubercle” or “granuloma.” The bacteria within the tubercle can survive for decades, and conditions leading to a weakened immune response can allow the bacteria to break out of the lesion and reactivate to develop into active TB. This gives rise to the prototypic symptom of TB – a persistent cough with blood in the sputum. At this point, the patient is highly infectious, spreading the bacteria by aerosol.

Question 2

Q

Describe the immunological basis of the tuberculin skin test.

Answer

A

The basis for the tuberculin skin test is T cell-mediated responsiveness to mycobacterial antigens. The test, however, lacks specificity due to cross-reactions with the M. bovis BCG vaccine and environmental mycobacteria.

Question 3

Q

What are pattern recognition receptors? List some of the agonist of pattern recognition receptors.

Answer

A

Pattern recognition receptors (PRRs) are a primitive part of the innate immune system (IIS). Toll-like Receptors (TLR’s) are the best characterized group of PRR’s. They are proteins expressed by cells of the IIS and are used to identify pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens. Some of the agonist of TLRs include polyinosine-polycytidylic acid, lipopolysaccharide, and imiquimod.

Question 4

Q

Describe the pathogenesis of active TB.

Answer

A

Infection occurs when a person inhales droplet nuclei containing tubercle bacilli that reach the alveoli of the lungs. These tubercle bacilli are ingested by alveolar macrophages; the majority of these bacilli are destroyed or inhibited. A small number may multiply intracellularly and are released when the macrophages die. If alive, these bacilli may spread by way of lymphatic channels or through the bloodstream to more distant tissues and organs. This process of dissemination primes the immune system for a systemic inflammatory response that is responsible for much of the suffering that TB patients suffer through.

Question 5

Q

What is IGRA? Do you think IGRA has advantages over the the tuberculin skin test? If so, please describe the major advantage. Are there disadvantages to this assay?

Answer

A

Interferon-Gamma Release Assays (IGRAs) are whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis infection. One disadvantage of the test is that it does not help differentiate latent tuberculosis infection from active tuberculosis disease. The test is also fairly expensive for developing nations. Two IGRAs that have been approved by the U.S. Food and Drug Administration (FDA) are commercially available in the U.S:

QuantiFERON-TB Gold In-Tube test (QFT-GIT);
T-SPOT.TB test (T-Spot)

IGRAs work by measuring IFN-γ released from antigen-specific T cells upon stimulation with M. tuberculosis antigen. IGRAs are attractive alternatives to TST for their improved specificity, pre- and post-analytical standardization, and logistical advantages.

Question 6

Q

Describe the laboratory methods to confirm active TB.

Answer

A

a) The AFB sputum smear - Sputum specimen is spun in a centrifuge and a small amount of the concentrate is “smeared” on a glass slide. The slide is then stained and washed with an acid solution. Finally, the slide is examined under a microscope.
b) Culture a sputum sample on a broth or medium that is favorable for TB growth.
c) Quantiferon Gold assay or TSpot assay
d) DNA amplification methods
e) PCR – Used to distinguish M. tuberculosis from other mycobacteria.
f) Fluorescent microscopy

Brainscape's Knowledge GenomeTM

In vitro Immunomodulation of a whole blood IFN gamma release assay enhances T cell responses in subjects with latent TB infection Flashcards

Brainscape's Knowledge Genome^TM