Lung infections

Question 1

what do surfactants do in the lungs

Answer 1

stop lungs sticking together and release opsonins that help phagocytosis

Question 2

how many alveoli are there and what is their approximate total surface area

Answer 2

approximately 300 million alveoli and their total surface area is about 140 m2

Question 3

what important clearance mechanisms are present in the lung

Answer 3

– the mucociliary escalator,
– coughing
– phagocytosis by alveolar macrophages.

Question 4

what are the two parts biphasic particle clearance

Answer 4

– fast (half life of minutes to hours) - tracheobronchial mucociliary clearance
– slow (half life days to thousands of days) - alveolar clearance

Question 5

the site of particle deposition determines……

Answer 5

…..the mechanism and rate of particle clearance

Question 6

particles of what size are able travel down to the alveoli

Answer 6

<5 microns

Question 7

what are the differences in the mucocilliary escalator in non CF and CF airways

Answer 7

in non cf airway - the depth of periciliary fluid is normal, islands of mucus float on top and are propelled towards to mouth by coordinated beating of cilia

in cf airway - decreased depth of periciliary fluid, the mucus is poorly hydrated and hypoxic. the compacted mucus inhibits cilia beating stopping the escalator. lower mucosal oxygens levels are good for some bacterial growth.

Question 8

what are some features of the cystic fibrosis lung

Answer 8

More fatty deposits, tissue disruption and redder colour

Question 9

give examples of the early and later colonisers of the CF lung

Answer 9

Early colonisers: Staphylococcus aureus, Haemophilus influenzae
Later colonisers: Pseudomonas aeruginosa, Burkholderia cepacia

Question 10

what bacterium appears to exacerbate lung infections

Answer 10

Burkholderia cepacia

Question 11

give four examples of bacterial pathogens that cause progression of pulmonary disease

Answer 11

Bulkholderia cepacia, Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus

Question 12

give some features of Pseudomonas aeruginosa

Answer 12

aerobic, motile, Gram-negative rod.
Able to grow and survive in almost any environment: lives primarily in water, soil, and vegetation.
Noted for its environmental versatility, ability to cause disease in susceptible individuals, and its resistance to antibiotics.

Question 13

what is the most serious complication of cystic fibrosis

Answer 13

respiratory tract infection with an Extracellular pathogen (goes into the body and doesn’t invade cells, reaping havoc) (eg Pseudomonas aeruginosa)

Question 14

what types of infections can be caused by Pseudomonas aeruginosa

Answer 14

ventilator-associated pneumonia, urinary and peritoneal dialysis catheter infections, bacterial keratitis, otitis externa, burn wound infections

Question 15

give examples of P. aeruginosa Virulence factors:

Answer 15

elastase, phospholipase C, protease A, exotoxins and cytotoxins, flagella and pili, pigment production, and QS regulatory system proteins

– biofilm structure & dynamics: aliginate, rhamnolipids
– immune evasion: elastase, alkaline protease
– antibiotic resistance: efflux pumps, modifying enzymes
– cytotoxicity: pyocyanin, T3SS, exotoxin A, HCN
– iron scavenging: proteases, siderophores
– Cell-associated/ motility (flagellum, pilus, non-pilus adhesins, lipopolysaccharide endotoxin [LPS])

Question 16

what is aliginate

Answer 16

alginate is an eps, helps form thick masses of biofilm, resides for long periods, and can trigger a big response. has the ability to scavenge host innate-immune reactive specie

Question 17

how are particles cleared in alveoli

Answer 17

there is no mucociliary clearance so particles are cleared by phagocytosis by alveolar macrophages

Question 18

what cells do intracellular pathogens commonly live and replicate in

Answer 18

– macrophages, dendritic cells, neutrophils,

– fibroblasts, epithelial or endothelial cells or erythrocytes.

Question 19

when was the first Legionnaires outbreak

Answer 19

21 July 1976 in Philidelphia (among american servicemen who attended a conference) - 221 people developed pneumonia and 34 died

Question 20

what are the Legionella-associated diseases

Answer 20

Legionnaires’ disease - acute fulminating pneumonia, low attack rate (>12% fatalities)
Pontiac fever - mild, non-pneumonic, febrile infection, high attack rate (resolves spontaneously and often goes undiagnosed.)

Question 21

what are most cases of legionella caused by

Answer 21

• 85% due to L. pneumophila sg 1

Question 22

what feature of Legionellaceae aids its waterborne spread

Answer 22

it remains motile at low temperatures

Question 23

what is the main outbreak source of Legionella

Answer 23

man made water distribution systems

Question 24

give some examples of other sources of legionella

Answer 24

– Circulating water droplets in air-conditioning and cooling systems.
– Showers (even baths as water splashes up)
– Whirlpool spas and other warm-water baths.
– Decorative fountains.
– Cooling towers. -specifically
– Nebulizers and humidifiers if topped up with contaminated tap water.
– Potting compost was the source of several outbreaks in Australia (L. longbeachae).

Question 25

what is a key feature of the legionella disease and why does it occur?

Answer 25

infects lung macrophages
previously in its evolution it was consumed by amoebae, so now when phagocytosed by macrophages they think they are in the amoebae and establishes a replication-permissive vacuole during or shortly after contact

Question 26

what virulence factors help legionella/ protozoa survive inside lung macrophages

Answer 26

KatA (periplasm) and KatB (cytosol) catalase/peroxidase maintain critically low H2O2
have a type 5 secretion ICM/DOT (intracellular multiplication/ defective organelle trafficking) complex that translocates effector molecules into host cells (requires ATP DotB) - also helps vacuole formation
Mip - macrophage infectivity protein

Question 27

describe the steps of L. pneumophilia pathogenesis and exit

Answer 27

• Ingestion by phagocytes, establish phagosomes completely isolated from endosomal pathway but surrounded by endoplasmic reticulum.
• Converts to replicative form that is acid tolerant but stops expressing virulence traits, including blocking membrane fusion
• Merges with lysosomes, provide nutrient rich replication niche
• Once deplete amino acids, secondary messenger ppGpp coordinates:
– entry into stationary phase (regulatory cascade involving LetA/LetS, RpoS, FliA, letE)
– transmission traits to exit and invade new phagocyte e.g. motility, IcmT membrane pore former, legiolysin (lly gene) and a zinc metalloprotease (Msp)

Question 28

give some features of Mycobacteria tuberculosis

Answer 28

weakly gram-negative, strongly acid-fast aerobic rod, multilobate colony-forming morphology with a 24-30 hour doubling time. have lipid-rich cells walls. resists biocides detergents and antibiotics

Question 29

give examples of 3 mycobacterial species and the diseases they cause

Answer 29

Mycobacterium tuberculosis causes tuberculosis
Mycobacterium leprae cause leprosy
Mycobacterium bovis causes tb in cows (BCG vaccine)

Question 30

what is BCG (vaccines)

Answer 30

Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against human tuberculosis but also for leprosy - made from M. bovis

Question 31

what is the infectious dose of M. tuberculosis

Answer 31

10 cells

Question 32

what are the classic symptoms of tuberculosis

Answer 32

chronic cough with blood-tinged sputum, fever, night sweats, weight loss

Question 33

who originally identified tuberculosis as consumption

Answer 33

Hippocrates in 460BC

Question 34

how does TB spread from person to person

Answer 34

infectious aerosol

Question 35

how does Legionella spread

Answer 35

in water/ water droplet inhalation

Question 36

what other organs can TB develop in other than the lung

Answer 36

kidney, genitourinary tract, joints, subarachnoid space.

Miliary TB: disseminates throughout body

Question 37

what are the three stages of M. tuberculosis infection

Answer 37

initial infection -> persistant or primary acute infection -> secondary acute infection

Question 38

describe teh three stages of M.tuberculosis lung infection

Answer 38

The first stage of M. tuberculosis infection involves the innate immune system, ingestion by resident macrophages and then multiplication of the bacterium within them.
Acquired immunity is involved in the second stage of the infection, here is where granulomas start to form with CD4+ CD8+ T cell recruitment as well as further macrophage activation. At this point, the immune system can control bacillary growth and prevents dissemination of the bacteria.
Immune suppression marks the beginning of the third and final stage which includes reactivation and rapid bacillary growth. After the hematogenous dissemination that spreads the pathogen all over the body comes secondary transmission the last occurrence before the bacterium take over and cause death of the patient

Question 39

what are granulomas and what’s their role in TB

Answer 39

Organized aggregates of mononuclear inflammatory immune cells that surround foci of infected tissues; limits further dissemination of M. tuberculosis but also provides a survival niche

Question 40

describe the progression of pulmonary tuberculosis (from implantation of tubercule bacilli)

Answer 40

• Tubercle bacilli on inhalation implant on bronchioles or alveoli through bronchial system
• Phagocytes (neutrophils and macrophages) engulf bacilli
• Bacilli multiply intracellularly and spread to lymph nodes, blood, and distant organs.
• In 2 weeks epithelial cells merge with macrophages forming granuloma (Ghon tubercle)
• Lymphocytes surround Ghon tubercle
• Central portion undergoes necrosis; cheesy appearance
• Liquefies and sloughs into connecting bronchus forming a cavity
(may enter tracheobronchial system – airborne transmission)
• Healing by resolution, fibrosis and calcification
• Scar formation around tubercle (Ghon complex)

Question 41

Why is M. tuberculosis such a successful pathogen?

Answer 41

factors that regulate the course and outcome of infection are manifold and involves a complex interplay between the immune system of the host and survival strategies by the bacteria
in host phagocytic cells like macrophages, M. tuberculosis interferes with the phagosome maturation pathway and thereby avoids destruction in the lysosome

Question 42

what TB control mechanism is recommended by WHO?

Answer 42

Directly observed treatment, short-course (DOTS)

Question 43

what are the components of TB-DOTS

Answer 43

Government commitment (including political will at all levels, and establishment of a centralized and prioritized system of TB monitoring, recording and training)
Case detection by sputum smear microscopy
Standardized treatment regimen directly of six to nine months observed by a healthcare worker or community health worker for at least the first two months
Drug supply
A standardized recording and reporting system that allows assessment of treatment results

Question 44

what are the cellular components of granulomas (in TB)

Answer 44

activated macrophages, multinucleated giant cells, CD4+ lymphocytes, Mycobacterium tuberculosis, CD8+ lymphocytes, epitheloid cells

Question 45

what is the chief mucus producing cell in the airway epithelium and what other cell aids the mucociliary clearance?

Answer 45

Goblet cells and ciliated cells aid