Pathogenesis of TB

• Define facultative.

  The ability of an organism to adapt to different environmental conditions. They can utilise the resources of the host cell to their advantage, but they are also capable of living independently
• Define non-motile.

  Organisms or cells that are not capable of movement on their own

  Do not possess means to move through their environment independently (lack flagella)
• What is an obligate aerobe?

  Organism that requires O2 to survive & grow
• What is a Ghon focus?

  1-2cm, cheese looking, white pulmonary parenchymal nodule with a nectrotic centre

  Usually close to the pleura
• What is a Ghon complex?

  Ghon focus associated with enlarged hilar lymph nodal involvement
• What is a Ranke complex?

  Ghon complex undergoes progressive fibrosis & calcification
• What is the doubling time of TB?

  18 - 24 hours
• What does the mycobacterium cell wall look like?

  Not gram positive or gram negative

  Has a peptidoglycan layer that is not as thick as gram +ve, but thicker than gram -ve

  Have a unique & complex outer cell wall - rich in mycolic acids
• All mycobacterium tuberculosis complex organisms are notifiable to Public Health England under Health Protection Regulations. Has to be reported within 3 days.
• The majority of people infected with Mycobacterium tuberculosis never develop any clinical symptoms.
• What are the infection sites of TB?

  Pulmonary TB - 85% of cases, may spread to other parts of the body

  Extrapulmonary TB - 15% of cases, occurs more in immunosuppressed people
• What are the most common sites of extrapulmonary TB?

  Miliary (disseminated)

  Lymph nodes

  Peritoneal TB

  Spine, bones & joints (Pott's disease)

  neuroTB

  Skin

  Genitourinary
• Define non-sporing.

  Does not produce spores
• What is an obligate anaerobe?

  Requires O2 to survive & grow
• What are the features of mycobacterium tuberculosis complex?

  Non-motile

  Non-sporing

  Obligate anaerobe

  Facultative intracellular organism

  Can remain dominant for decades

  Slightly curved bacillus, 1-5 µm
• What is another name for cord factor?

  TDM

  Trehalose dimycolate
• What is so different about the TB cell wall?

  Not gram -ve or +ve

  High lipid content (60%)

  Contains;

  • mycolic acid
  • peptidoglycan
  • arabinogalactan
  • trehalose dimycolate (cord factor)
• What is mycolic acid?

  Waxy coat

  Makes cell less permeable & highly resistant to antibiotics
• Peptidoglycan in TB cell wall

  Confers rigidity & maintains shape
• Arabinogalactan in TB cell wall

  Helps the bacteria to survive inside macrophages
• Why does cord factor help TB survival?

  Helps evade immune response

  Triggers cytokine release

  Causes chronic granulomas
• What is shown in this image?

  Cord factor

  
• 1/3 world's population are infection with TB and at risk of developing active TB
• Fill in the blanks

  A) Infection

  B) No infection

  C) Active TB

  D) Latent TB

  E) Latent

  F) Active

  
• What is Potts disease?

  Spinal tuberculosis
• What is miliary TB?

  Widely disseminated form of TB
• What is lupus vulgaris?

  Skin tuberculosis
• What is lymphadenitis?

  Enlargment of 1 or more lymph nodes
• What is opisthotonos?

  Spasm of the muscles causing backward arching of head, neck & spine
• What are the 4 potential fates of inhaled TB bacilli?

  Initial host response kills all bacteria -> no chance of active TB developing

  Organisms begin to multiple immediately -> primary TB

  Bacilli become dormant & never cause disease -> latent TB

  Latent organisms eventually grow with resultant clinical disease -> reactivation TB
• How are sputum samples used to diagnose TB?

  At least 2 separate sputum samples (ideally early morning samples)

  Specimens can be contaminated with resident flora, so need a decontamination step before culture
• What are the symptoms of TB?

  Persistent cough

  Fever

  Night sweats

  Weight loss

  Chets pain

  Fatigue

  Loss of appetite

  Coughing blood
• What does TB look like in culture?

  Colonises dry, raised, irregular, white or yellow

  
• What is MALDI-TOF? How is it used?

  Matrix assisted laser desoprtion ionisation - time of flight

  Analyses 16s ribosomal proteins & compared test strains against known resistance strains

  Only used in some labs
• What is WSG? How is it used?

  Whole Genome Sequencing

  Determines the complete DNA sequance of an organism's genome

  Only available in specialist labs on request
• What is IGRA?

  Interferon-Gamma Release Assay

  Blood test used to detect TB infection

  Pt is given synthetic antigens -> measure amoutn of IFN-y (produced by T cells)

  Cannot differentiate between latent infection & active TB disease
• What is TST?

  Tuberculin Skin Test

  Skin test

  Inject small amount of TB antigen under the skin & measure immune response after 48-72 hours

  Cannot differentiate between latent infection & active TB
• Initial infection of TB

  Inhalation of droplet nuclei expectorated from respiratory tract of an active TB suffered

  Only droplet nuclei of 1 - 5 µm in diamter (containing 1 - 3 bacilli) to reach alveoli

  Larger particles are trapped by the nasopharynx & upper respiraoty tract
• What are the risk factors of TB?

  Socioeconomic status - poverty, overcrowding, poor living conditions, malnutrition, lack of adequate healthcare, incarceration

  Overall health/immune system status - immunosuppression, HIV, diabetes, TB within last 2 years, transplant patients, malignancy

  Alcoholism

  Smoking

  Drug users

  Mental health

  Healthcare workers

  Genetic predisposition
• 1. Immune system eliminates bacteria

  Phagocytosis of bacteria by alveolar macrophages (via various receptors) -> bacteria with fuse with lysosome -> death of bacteria -> no TB