Lecture 15: Tuberculosis Flashcards
Describe the TB pandemic?
1/3 of the world population is infected with TB. Most of this is latent. 1.5million have disease/illness at any time and 96% of TB deaths are in the developing world.
Whats the classification of mycobacterium?
- TB
- Non-tuberculous mycobacterium
- Rapid growing
- Non-rapid growing
- Other
Describe steps 1-4 of TB infection
1) Aerosolised TB particle inhaled
2) Particle impacts in distal airway
3) TB is engulfed (phagocytosed) by pulm. alv. macrophage. ((TB cell wall constituents initiate phagocytosis + complement receptors + Mannose receptors))
4) TB resists lysis by lysosome
How does TB resist lysis by lysosome?
Array of factors that enable TB to survive intracellularly and to induce the macrophage to remain alive. i.e
- Blocks H pump of vesicles and alters fusion with phagosome i.e prevents macrophage lysis of TB.
- TB has tough cell wall, free radical scavengers, superoxide dismutase
- Stimulates LAM to decrease apoptosis and prevent antigen presentation through MHC 2.
Describe step five of TB infection (Early stages)
TB survives within macrophages.
- Mast cells activated by stimulated macrophage release TNFa
- TNFa recruits other macrophages and neutrophils which release further cytokines
- Local dendritic cells and histiocytes are activated
- Lots of chemokines are produced and further cells are recruited.
- Dendritic cells loaded with antigen head to lymph nodes and stimulate T cells (minutes to hours after bacteria inhaled)
i.e
In early TB the infection is carried to the local lymph nodes
Describe steps 6 and 7 of TB
6) In lymph node D.C release IL1-2 which causes T cell proliferation and differentiation into CD4 T cells.
7) In hours to days T cells traffic to sites where microcirculation has been altered by TNFa and other chemokines.
Describe step 8 of TB
8) Activated T cells interact with macrophages and IFNgamma and TNFa cause macrophage maturation.
- In days to weeks granulomas are formed. i.e Immune system cant quite kill TB and instead builds a prison of immune cells around it (granuloma).
Write some notes on what is present in the granuloma;
Macrophages surround necrotic tissue that has dormant / slowly replicating TB / persistant antigen. These epitheliod macrophages can fuse in spots becoming multinucleated.
The epitheliod macrophages are surrounded by T cells which release TNFa to keep the macrophages happy.
Give an overview / flow chart of TB (Refer to slides 14) good to reproduce….
Primary infection -> Primary complex ((granuloma)(Gohn focus))-> Immune containment-> No disease, latent TB infection.
-> Reactivation (Factors; Age, HIV, Cancer, Steroids, Anti-TNFa (Cus of CD4))
= Illness
What can TB lead to?
- Miliary TB (Dissemenated)
- Extra pulmonary TB (Adenitis, Osteomyelitis, kidney etc)
- Pulmonary/thoracic TB
Describe step 9 of TB
9) Outcome of primary infection
A) Primary focus (Gohns focus) = Lung + Node B) Pleural C) Cavitation D) Symptoms from increasing nodes E) TB bronchopneumonia F) Pericardial disease G) Miliary = Dissemenated
(Tends to be top of the lung because oxygen profile is higher, gravity, less blood flow therefore increased O2)
What are the risks of people for catching TB?
- Household contact
- Children
- Immune suppression
- Institutional care
- Healthcare workers
How should TB be diagnosed?
1) Suspicion (Fever, cough)
2) Chest X-ray
3) Sputum specimens (AFB)
4) TB PCR
5) TB culture (days to weeks)
Whats a feature of the mycobacterium cell wall? and whys it important in staining.
Has a fatty layer in the cell wall. Thus carbo-fuchsin stain sticks to lipid cell wall. Most other bacteria lose CF stain.
Acid fast staining
What is the Mann-2-test?
Tb protein PPD is given intradermally.
Reviewed in 72hrs and if inflammatory response is present the person is hypersensitive to TB antigen.
