An overview of tuberculosis: infection, immune response and preventive strategies Flashcards
Describe the properties of Mycobacterium tuberculosis
*acid-fast bacilli (rods) - The high lipid content (mycolic acids) of their cell wall makes mycobacteria acid-fast.
*gram-positive bacterium
*grows slowly
* obligate aerobe - explain the causing disease in highly oxygenated tissues such as the upper lobe of the lung and the kidney.
*Cord factor (trehalose dimycolate) is correlated with virulence of the organism.
*relatively resistant to acids and alkalis. resistant to dehydration and therefore survives in dried expectorated sputum
Describe the transmission of Mycobacterium tuberculosis
- transmitted from person to person by respiratory aerosols produced by coughing
- Risk factors: household sharing and crowding
- The portal of entry is the respiratory tract
and the initial site of infection is the lung.
Describe the pathogenesis of Mycobacterium tuberculosis
Mycobacterium tuberculosis produces no exotoxins and does not contain endotoxin in its cell wall. The organism preferentially infects macrophages and other reticuloendothelial cells.
Mycobacterium tuberculosis survives and multiplies within a phagosome. The organism produces a protein called “exported repetitive protein” that prevents the phagosome from fusing with the lysosome, thereby allowing the organism to escape the degradative enzymes in the lysosome.
what are the outcomes of primary and secondary TB?
primary tuberculosis which typically results in a Ghon focus in the lower lung. Primary tuberculosis can heal by fibrosis, can lead to progressive lung disease, can cause bacteremia and miliary tuberculosis, or cause hematogenous dissemination resulting in no immediate disease but with the risk of reactivation in later life.
secondary tuberculosis with a cavity in the upper lobes. This can cause disease directly or result in reactivation disease in later life with central nervous system lesions, vertebral osteomyelitis (Pott’s disease), or involvement of other organs.
Where do LTBI bacteria reside?
- There is no clearcut evidence as to where LTBI reside
- It is thought that LTBI may consist of multiple bacillary populations, those growing rapidly and those metabolically inactive
- Conventional view is that the bacteria reside in lung macrophages
- Alternative view: extracellular localisation within lung tissue, similar to ‘persister’ bacilli during drug treatment
- However, some evidence suggests bronchial lymph nodes and tonsils
- Recent studies detected MTB in autopsies from spleen, liver and kidneys
- MTB DNA was also detected in adipose tissues surrounding stomach, heart, kidneys and skin
- Thus LTBI may represent a spectrum of asymptomatic conditions with varying risk of reactivation
Risk factors for reactivation of TB?
- Malnutrition
- Poverty
- Immunosuppression
- Diabetes
- Old age
- Poor health
- HIV
The difference between latent TB infection and active TB Disease?
Other than the lungs what are other sites infection?
-larynx
-lymph nodes
-kidneys
-brain & spine
-bones & joints
Describe the Ghon focus
Initial infection with Mycobacterium tuberculosis in an immunocompetent individual usually occurs in an upper region of lower lobe of the lung producing a lesion called a Ghon focus
Granulomatous involvement of peribronchial and/or hilar lymph nodes is frequent in primary tuberculosis due to lymphangitic spread from the Ghon focus.
The early Ghon focus together with the lymph node lesion constitute the Ghon complex
These lesions undergo healing and over time usually evolve to fibro- calcific nodules.
When does miliary TB occur?
Miliary tuberculosis, as seen here, typically occurs when resistance to mycobacterial
infection is poor and often in children as consequence of primary disease
what does Pulmonary Tuberculosis look like on a CT scan?
What does TB look like in the brain and meninges?
Name the disease for:
1. TB diseases of the spine
2.Lymph node TB
- Potts disease
- Scrofula
Immuno-Pathogenesis of MTB infection
- Inhalation
- Alveolar macrophages
- Lymph nodes
- Haematogenous spread to other parts of lung via lymphatics and capillaries
- A brief acute inflammatory response -
neutrophils, cytokine storms
macrophage recruitment and activation - recruitment of CD4, CD8 and NK cells - production of IFN-y
- Down regulation of acute inflammation → chronic inflammation
- Formation of granuloma - immune containment
- Caseation
- Liquefaction, cavitation and release
- Transmission
explain how the Immune response in TB is a ‘double-edged sward’
Good
➢Innate immunity: alveolar macrophages kill ingested bacilli
➢Th1 adoptive immune response: CD8 and CD4 T cells, IFN-gamma: essential for controlling infection
Bad
Excessive immune response leads to overproduction of TNF-alpha and healthy
tissue damage and fibrosis (immunopathology of TB).
Describe Killing by phagocytosis and phago-lysosome fusion
Most efficient phagocyte for killing MTB, but also shelter for bacteria (because
MTB evolved strategies for avoiding intracellular killi
What is the purpose and downside of Tuberculous Granuloma
Containment of infection but also leads to tissue damage
Describe the Granuloma composition
An immunological granuloma typically has a core of epithelioid cells and macrophages, sometimes with giant cells. In some diseases, such as tuberculosis, this central area may
have a zone of necrosis, with complete destruction of all cellular architecture.
The macrophage/epithelioid core is surrounded by a cuff of lymphocytes, and there may also be considerable fibrosis
(deposition of collagen fibers) caused by proliferation of fibroblasts and increased collagen synthesis.
TNF and the related cytokine, lymphotoxin-a, are both essential for the formation of granulomas during mycobacterial infections
the Liquefaction of granuloma and cavitation lead to transmission
What are the difficulties in testing TB vaccines in
animal models
