BK - Lung Infection Flashcards
How do mechanical factors prevent infections? (3)
Mechanical factors form the first line of defense against pathogens:
- Epithelial surfaces: Skin acts as a barrier, while shedding of skin cells removes microbes
- Mucus and cilia: Mucus traps microbes, and cilia in airways move mucus upward for expulsion
- Flushing action: Tears and saliva help wash away microbes from the eyes and mouth
How do chemical factors hinder pathogens? (4)
Chemical factors create an unfriendly environment for pathogens:
- Antimicrobial substances: Lysozyme and phospholipase in tears, saliva, and elsewhere can destroy bacteria
- Low pH: Stomach acid creates an acidic environment that kills many bacteria.
- Fatty acids: Fatty acids in sweat inhibit bacterial growth
- Surfactants in the lung act as opsonins (aid phagocytosis)
How does normal flora protect against infection?
Normal flora, the resident microorganisms on skin and in the gut, compete with pathogens for space and nutrients, hindering their colonization
How does the lung clear inhaled particles? (3)
The lung has efficient clearance mechanisms:
- Mucociliary escalator: Mucus traps particles, and cilia move it upwards for expulsion.
- Coughing: A forceful expulsion of air that helps clear airways.
- Phagocytosis by alveolar macrophages: Phagocytes engulf and destroy particles in the alveoli.
How is particle clearance biphasic?
- fast (half life of minutes to hours) - tracheobronchial mucociliary clearance
- slow (half life days to thousands of days) - alveolar clearance
How does cystic fibrosis (CF) affect lung infections?
Shortly after birth of people afflicted with CF, mucus in the bronchial tree stagnates in the smaller bronchioles
leads to early infection with:
- Staphylococcus aureus
- Haemophilus influenzae
and later on (< 10 years) with:
- Pseudomonas aeruginosa
- Burkholderia cepacia (co-infection)
What are the characteristics of Pseudomonas aeruginosa?
Pseudomonas aeruginosa is a versatile, antibiotic-resistant bacterium that can cause severe infections in CF patients and others with compromised immune systems
- Habitat: Lives in water, soil, and vegetation.
- Virulence factors: Produces toxins that damage tissues and suppress immune responses.
- Biofilm formation: Forms biofilms in the lungs, promoting chronic inflammation.
What are some features of biofilms in vivo? (3)
“Slime” Glycocalyx
Adhesion
Protection from:
- macrophages etc
- biocides
- antibiotics
- bacteriophage
How do intracellular pathogens differ from extracellular pathogens?
- Intracellular pathogens live and replicate inside host cells, evading some immune defenses. Examples include viruses, some bacteria, protozoa, and fungi
- Extracellular pathogens live outside host cells, like Pseudomonas aeruginosa
How do macrophages defend against pathogens?
Macrophages are phagocytes that engulf and destroy foreign particles, including bacteria
What are 2 examples of Legionella-associated disease?
Legionnaires’ disease - acute fulminating pneumonia
- low attack rate (>12% fatalities)
Pontiac fever - mild, non-pneumonic, febrile infection
- high attack rate
What is the main source of legionella?
Outbreak source is usually a man-made water distribution system where the bacteria have multiplied in great numbers e.g. warm storage tanks where the water stagnates; piped water, especially hot water, in large buildings with long runs of pipework
What is a survival strategy of L.pneumophila within macrophages? (5)
- L. pneumophila triggers phagocytosis
- Establishes a replication-permissive vacuole (phagosome) during or shortly after initial contact
- (inhibits phagosome/lysosome fusion – no enzymes, free radical release).
- Formation of the vacuole is dependent on the bacterial icm/dot (intracellular multiplication/ defective organelle trafficking) genes
- Encodes a secretion apparatus related to type IV conjugation systems
How does Legionella pneumophila exploit macrophages for survival and replication? (6)
1) Ingestion: Legionella gets taken up by macrophages through phagocytosis.
2) Replicative vacuole formation: Instead of being destroyed in lysosomes, Legionella cleverly blocks the fusion of the phagosome with lysosomes. This creates a unique compartment suitable for its replication.
3) Amino acid depletion: Legionella utilizes the macrophage’s resources for growth, particularly amino acids.
4) Secondary messenger activation: Once amino acids become scarce, Legionella triggers the production of a secondary messenger called ppGpp.
5) Regulatory cascade: ppGpp initiates a signaling cascade involving proteins like LetA/LetS, RpoS, FliA, and letE.
6) Shifting gears: This cascade has two key outcomes:
- Entry into stationary phase: Legionella slows down its growth and prepares for a more stressful environment.
- Transmission traits activation: Genes for virulence factors like motility, IcmT (membrane pore former), legiolysin (lly gene), and a zinc metalloprotease (Msp) are expressed.
What are 4 features of Mycobacterium tuberculosis?
- Weakly Gram-negative
- Strongly acid fast aerobic rod
- Multi-lobate colony morphology
- 24-30 hour doubling time
