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What is the primary characteristic of latent tuberculosis?
What is the primary characteristic of latent tuberculosis?
What distinguishes extrapulmonary tuberculosis from pulmonary tuberculosis?
What distinguishes extrapulmonary tuberculosis from pulmonary tuberculosis?
Which of the following represents a major risk associated with latent tuberculosis?
Which of the following represents a major risk associated with latent tuberculosis?
Which form of tuberculosis is characterized as a potentially widespread disease?
Which form of tuberculosis is characterized as a potentially widespread disease?
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Which mycobacterial infection is primarily associated with swollen, nontender lymph nodes?
Which mycobacterial infection is primarily associated with swollen, nontender lymph nodes?
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What was the approximate number of new cases of tuberculosis reported in 2016?
What was the approximate number of new cases of tuberculosis reported in 2016?
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Which of the following factors contribute to the emergence of drug-resistant tuberculosis?
Which of the following factors contribute to the emergence of drug-resistant tuberculosis?
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What is the leading cause of death globally resulting from a single infectious agent since 2014?
What is the leading cause of death globally resulting from a single infectious agent since 2014?
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What characteristic of Mycobacterium tuberculosis contributes to its classification as acid-fast?
What characteristic of Mycobacterium tuberculosis contributes to its classification as acid-fast?
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Which of the following describes the morphology and staining characteristics of Mycobacterium tuberculosis?
Which of the following describes the morphology and staining characteristics of Mycobacterium tuberculosis?
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What is the primary mode of transmission for Mycobacterium tuberculosis?
What is the primary mode of transmission for Mycobacterium tuberculosis?
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Which population is at an increased risk for contracting tuberculosis due to a weakened immune system?
Which population is at an increased risk for contracting tuberculosis due to a weakened immune system?
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Which staining method is commonly used to identify acid-fast bacilli like Mycobacterium tuberculosis?
Which staining method is commonly used to identify acid-fast bacilli like Mycobacterium tuberculosis?
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What is the role of mycolic acids in Mycobacterium tuberculosis?
What is the role of mycolic acids in Mycobacterium tuberculosis?
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What is a less common method of transmission for Mycobacterium tuberculosis?
What is a less common method of transmission for Mycobacterium tuberculosis?
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What is the primary characteristic of Mycobacterium tuberculosis's respiratory pathogenicity?
What is the primary characteristic of Mycobacterium tuberculosis's respiratory pathogenicity?
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What is the purpose of the virulence factors released by mycobacteria?
What is the purpose of the virulence factors released by mycobacteria?
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What is a Ghon's complex?
What is a Ghon's complex?
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How long does it typically take for adaptive cellular immunity to develop after tuberculosis infection?
How long does it typically take for adaptive cellular immunity to develop after tuberculosis infection?
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What characterizes a Ranke complex in tuberculosis?
What characterizes a Ranke complex in tuberculosis?
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What role do granulomas play in tuberculosis infection?
What role do granulomas play in tuberculosis infection?
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Which group of individuals is considered more susceptible to tuberculosis due to a weaker immune system?
Which group of individuals is considered more susceptible to tuberculosis due to a weaker immune system?
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What can occur if the cell-mediated immunity fails to clear the initial tuberculosis infection?
What can occur if the cell-mediated immunity fails to clear the initial tuberculosis infection?
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What factor is closely linked to tuberculosis as a disease of poverty?
What factor is closely linked to tuberculosis as a disease of poverty?
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What is the role of the mycobacterial urease in tuberculosis virulence?
What is the role of the mycobacterial urease in tuberculosis virulence?
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Which cells are primarily responsible for the protective immune response against M. tuberculosis?
Which cells are primarily responsible for the protective immune response against M. tuberculosis?
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What is the effect of lipoarabinomannan (LAM) on macrophages during tuberculosis infection?
What is the effect of lipoarabinomannan (LAM) on macrophages during tuberculosis infection?
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What does the presence of cord factor in M. tuberculosis correlate with?
What does the presence of cord factor in M. tuberculosis correlate with?
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What is the importance of activated macrophages in the response to M. tuberculosis infection?
What is the importance of activated macrophages in the response to M. tuberculosis infection?
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What cellular structure is formed from fused macrophages in a granuloma during tuberculosis infection?
What cellular structure is formed from fused macrophages in a granuloma during tuberculosis infection?
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Which cytokines are crucial for an effective immune response against M. tuberculosis?
Which cytokines are crucial for an effective immune response against M. tuberculosis?
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What is the initial barrier M. tuberculosis must overcome after inhalation?
What is the initial barrier M. tuberculosis must overcome after inhalation?
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Study Notes
Objectives
- Describe the properties, pathogenesis, and clinical significance of Mycobacterium tuberculosis as respiratory pathogens.
Mycobacterium tuberculosis
- Mycobacterium tuberculosis was first identified by Robert Koch.
- There are more than 100 species of mycobacteria.
- The name "mycobacteria" means fungus-like bacteria, derived from their mold-like appearance when grown in liquid media.
- They are also called acid-fast because they resist decolorization by dilute mineral acids due to the rich lipid content (mycolic acids, waxes, and phosphatides) in their cell walls.
Morphology
- Size: 3 microns in length and 0.3 microns in width.
- Shape: Straight or slightly curved rod.
- Arrangement: Singly, pairs, or small clumps.
- Nonmotile, nonsporing, and non-capsulated.
- Staining reaction: Ziehl Neelsen staining.
- Acid fastness, beaded forms commonly seen.
- Fluorescent stain: Auramine Rhodamine stain.
Pathogenesis - Mode of Infection
- Almost all M. tuberculosis infections result from inhaling droplet nuclei (infectious particles) from a person with pulmonary TB (coughing, sneezing, talking).
- These dried droplet nuclei remain airborne and reach the terminal air passages.
- The infection occurs by inhaling aerosolized bacilli contained in droplet nuclei of expectorated sputum.
- Coughing, sneezing, etc., release about 3000 droplet nuclei.
- Processing clinical specimens in the lab and other procedures can lead to infection.
- Ingestion can also occur by infected milk (e.g., M. bovis).
Transmission
- Person-to-person via the air.
- Less frequently through ingestion of unpasteurized milk products.
- Laboratory accidents can also lead to infection.
Environmental Factors
- Concentration of infectious droplet nuclei: Higher concentration increases transmission probability.
- Space: Exposure in small, enclosed spaces increases transmission risk.
- Ventilation: Inadequate local or general ventilation reduces dilution and removal of infectious droplet nuclei.
- Air circulation: Recirculation of air containing infectious droplet nuclei increases transmission risk.
- Specimen handling: Improper procedures generate infectious droplet nuclei.
- Air pressure: Positive air pressure in infectious patient rooms can cause M. tuberculosis to flow to other areas.
Virulence Mechanisms
- Ability to survive within macrophages.
- Phagosome acidification: Mycobacterial urease helps prevent acidification, limiting the effectiveness of bactericidal enzymes.
- Phagosome-lysosomal fusion: The organism produces an exported repetitive protein to prevent fusion, allowing it to escape degradative enzymes in the lysosome.
- Cord formation (trehalose dimycolate): Correlates with virulence. A cord factor inhibits leukocyte migration and causes chronic granulomas.
- LAM (lipoarabinomannan): Inhibits macrophage activation by interferon gamma.
- The organism secretes various antioxidants (superoxide dismutase, catalase) to detoxify reactive oxygen species generated by phagocytes.
- Phosphatidase plays a role in caseous necrosis.
Immunology
- TB requires a cellular immune response for control.
- Effective immune response relies on CD4+ T cells and cytokines (interleukin-12, interferon-gamma, tumor necrosis factor).
- CD4+ Th1 cells secrete interferon-gamma, crucial for the protective immune response against M. tuberculosis.
- Activated macrophages accumulate high concentrations of lytic enzymes and reactive metabolites, increasing mycobactericidal competence.
- Epithelioid cells (characteristic of tuberculous granuloma) are highly stimulated macrophages.
- Langhans giant cells are fused macrophages oriented around TB antigens.
- Cellular immune responses also cause tissue damage and pulmonary cavity formation.
Mechanism
- After inhalation, M. tuberculosis must bypass mechanical barriers (ciliated respiratory epithelial cells, mucins) to reach alveolar spaces.
- In alveoli, M. tuberculosis is phagocytized by alveolar macrophages.
- Alveolar macrophages sometimes successfully kill M. tuberculosis through phagosome maturation and lysosome fusion.
- Alternatively, M. tuberculosis may release virulence factors to delay phagosome maturation.
- M. tuberculosis uses several strategies to survive within macrophages while delaying or preventing an effective immune response
Primary Tuberculosis
- Initial infection, unrestrained replication for weeks in the initial focus and lymphohematogenous metastatic foci.
- Delayed adaptive cellular immunity development (4-8 weeks).
Pathogenesis of Tuberculosis
- After 3 weeks of infection, cell-mediated immunity develops, forming epithelioid granulomas (with T cells, macrophages, and giant cells); central caseation and peripheral fibrosis (called Ghon focus).
- Ghon focus location: Upper part of the lower lobe or lower part of the upper lobe is typical.
- Ghon's complex: If Ghon's focus involves adjacent lymphatics and hilar lymph nodes, it is known as Ghon's complex or primary complex.
- Ranke complex: If Ghon's complex undergoes fibrosis and calcification, it is referred to as a Ranke complex.
Macrophages and Granulomas
- Macrophages, epithelioid cells, T lymphocytes, and fibroblasts aggregate to form granulomas with lymphocytes surrounding infected macrophages.
- Fused macrophages form giant multinucleated cells in the alveolar lumen.
- Granulomas prevent dissemination of M. tuberculosis.
- Bacteria can become dormant in granulomas, leading to latent infection.
Spread of Mtb in the Body
- A tubercle can erode into a bronchus, emptying caseous contents and spreading organisms to other lung portions, or the gastrointestinal tract if swallowed.
M.tuberculosis as an Opportunistic Organism
- Decreased immunity (e.g., HIV, chronic steroid use) increases susceptibility to tuberculosis.
- Children, elderly, and pregnant women are more prone due to a weaker immune system.
- TB is closely linked to overcrowding and malnutrition.
Burden of Tuberculosis
- M. tuberculosis infects about one-quarter of the world's population.
- Approximately 10.4 million new TB cases and 1.7 million deaths in 2016.
- Leading cause of death worldwide (above HIV).
- Immunocompromised individuals (e.g., HIV-infected) are at high risk for TB.
Atypical Mycobacteria
- Mycobacterium tuberculosis, M. leprae, and other atypical mycobacteria (e.g., M. avium-intracellulare complex, M. kansasii) cause tuberculosis-like disease.
- Mycobacterium chelonae is a rapidly growing atypical mycobacterium.
- More than 170 Mycobacterium species exist.
Clinical Significance of Tuberculosis
- Pulmonary TB: Chest pain, coughing up blood or sputum, fatigue, weight loss, anorexia, fever, night sweats.
- Extrapulmonary TB : Central nervous system (tuberculous meningitis), lymphatic system (scrofula), genitourinary system, bones and joints (Pott disease).
Scrofula
- Cervical lymphadenitis (swollen, nontender lymph nodes, usually unilateral) caused by TB.
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Description
This quiz covers the properties, pathogenesis, and clinical significance of Mycobacterium tuberculosis, a crucial respiratory pathogen. It includes details about its morphology, staining techniques, and infection mode. Test your understanding of this important bacterium.
