Medical Micro - Lung/gut Flashcards
what are mechanical factors in the lung that act as a barrier to disease
epithelial surfaces
movement of cilia
trapping effect of mucus
what are chemical factors in the lung that act as a barrier to infections
fatty acids
lysozyme and phospholipase
low pH
surfactants in the lungs act as opsonins
what are the biological factors that prevent infections
normal flora in the skin/GI tract
what are the clearance mechanisms in the lungs
mucociliary escalator
coughing
phagocytosis via alveolar macrophages
particle clearance in the lungs is biphasic - what does this mean
fast (half life of minutes - hours) - tracheobronchial mucociliary clearance
slow (half life of days - years) - alveolar clearance
what is the rate and mechanism of particle clearance in the lung in part determined by
the site of particle deposition
what is the difference in mucus in a non-CF vs CF lung
non-CF - depth of periciliary fluid is normal, mucus floats to the top and is co-ordinated towards the mouth via cilia
CF - mucus is poorly hydrated and hypoxic, compacted mucus inhibits cilia beating
what happens shortly after birth to those born with CF
mucus in the bronchial tree stagnates in the smaller bronchioles
what are the early infections that CF leads to
staphylococcus aureus
haemophilus influenzae
what are the later on infections that CF leads to
pseudomonas aeruginosa
burkholderia cepacia
what is the main reason of death due to CF
progression of pulmonary diseases via bacterial infection
what are the main features of pseudomonas aeruginosa
motile
aerobic
gram-negative
where does P. aeruginosa live
almost any environment
primarily in water, soil and vegetation
what type of pathogen is P. aeruginosa
opportunistic pathogen
infects individuals with immune system deficiencies
common for cancer/burn patients
what are the P. aeruginosa virulence factors
produces toxins that kill host cells
extensive tissue damage via degrative enzymes
alginate production causes thick biofilms which causes chronic inflammation response
where do intracellular bacteria live and replicate
either in endosomal compartments
or in cytosol of diverse amount of host cells
what are classified as intracellular pathogens
all viruses
many bacterial pathogens
certain protozoa and fungi
how are particles cleared from the alveoli
cleared by phagocytic cells
including alveolar macrophages
what are the features of legionnaires disease
acute fulminating pneumonia
low attack rate (>12% fatalities)
features of pontiac fever
mild
non-pneumonic
febrile infection
high attack rate
how is legionella contracted
by breathing water droplets containing legionella bacteria
what is the main thing legionella infects
lung macrophages
after phagocytosis into the macrophage, what are the survival strategies used by L. pneumophila inside the macrophage
establishes a replication-permissive vacuole
during/shortly after initial contact
inhibits lysosome/phagosome fusion - no enzyme/free radical release
what is formation of the vacuole in macrophages by L. pneumophila dependant on
bacterial icm/dot (intracellular multiplication/defective organelle trafficking) genes
what are pilin genes required for
attachment to host cells and biofilms
intracellular growth
what is type IV secretion icm/dot complex and what is required for it
membrane spanning
translocates effector molecules into host cells
requires ATPase DotB
what do DotA/B mutants still infect
A. castellani
name the virulence determinants for invasion and growth
flagella expression
type IV secretion
pilin genes
macrophage infectivity protein (Mip)
KatA/KatB
where are KatA/B located
KatA - periplasm
KaB - cytosol
what happens when L. pneumophila converts to replicative form
it is acid tolerant
stops expressing virulent traits
what happens once L. pneumophila is ingested by a phagocyte
is converted to a replicative form
merges with the lysosome and replicates in there because it is a nutrient rich environment
what happens once the amino acids in the lysosome are depleted by L. pneumophila
secondary messenger - ppGpp coordinates entry into stationary phase
what does entry into stationary phase for L. pneumonia lead to
transmission traits to exit and invade new phagocyte
host cell implodes
features of TB
weakly gram negative
strongly acid fast aerobic rod
multi-lobate colony morphology
24-30 hour doubling time
what is unusual about the mycobacterium (i.e. TB) cell wall
unusual cell wall lipids
thick layer of mycolic acids
what is mycolic acid composed of
polymer sugars
N-acetylglucosamine
amino acids
what is the function of the mycolic acid layer
gives resistance to:
biocides
detergents
antibiotics
name some infections caused by mycobacterium
TB
leprosy
BCG
where do tubercle bacili implant themselves upon inhalation
bronchioles
alveoli
what occur to the bacili after attachment in the lungs
they are engulfed by neutrophils/macrophages
what happens to bacili after they are engulfed by phagocytes
multiply intracellularly
spread to lymph nodes, blood and distant organs
what happens 2 weeks after tubercle bacili multiple and spread
forms ghon tubercle:
epithelial cells merge with macrophages forming a granuloma
what surrounds Ghon tubercle
lymphocytes
what happens to the central portion of the ghon tubercle
undergoes necrosis
gets a cheesy appearance
what is the effect of the necrosis that the ghon tubercle undergoes
liquefies and spills into connecting bronchus
forms a cavitvy
what are the sites of primary/secondary biofilm infections
mouth
subvenous cathether
artificial hip implant
what does plaque flora affect and what does it cause
teeth:
malodour
tooth decay
gum disease
loss of teeth
what are the similarities/differences between H. pylori and E. coli/C. difficile
similarities - effect stomach intestine colon
differences:
H. pylori - causes gastric ulcers
others - cause gastroenteritis
what does P. aeruginosa affect and what does it cause
upper respiratory tract:
cystic fibrosis - death
what does streptococci/yeasts/fungi affect and what does it cause
heart valves:
endocarditis - death
what does gonococci/candida/treponema affect and what does it cause
urethral/cervical epithelium:
gonorrhoea
thrush
syphilis
death
what does staphylococci/streptococci/baciluss/proteus affect and what does it cause
bone:
deep seated abscess
osteomyelitis
septicaemia
death
what does dental plaque inflammation lead to
gingivitis
periodontal disease
what are the physical barriers for dental health
keratinized epithelium
mucin production
salivary flow
what are the chemical barriers for oral health
salivary enzymes
antibacterials
gingival fluid secretions
what is a non-chemical/physical oral defence system
inflammatory reaction
what is caries
its a dental disease associated with poor hygiene and high sugar diet
results in holes in teeth
what are periodontal diseases
it is a non-destructive gingivitis
caused by poor hygiene
leads to inflamed and bleeding gums
what is destructive periodontitis
usually occurs as people get older
leads to gum and bone loss
what are saccharolytics
metabolise sucrose and other sugars
what are the difference between acidogenic and aciduric
acidogenic - ferments to produce lactic/acetic/formic acids to lower pH
aciduric - metabolise and grow at low pH
what are the differences between gluco/fructotransferase as a streptococcal virulence factor
gluco - EPS glucan/mutan to form biofilm
fructo - EPS frucatn/insulin to form plaque biofilm
what are the virulence factors of streptococcal in carious plaque
saccharolytics
glucosyltranferase
fructosyltransferase
acidogenics
acidurics
features of veillonella
gram-negative anaerobic cocci
thrives in the acidic environment of caries
slows down the formation of caries
converts lactic acid to less acidic products
features of lactobacillus
gram-positive, anaerobic
normally a part of the gut flora
some strains cause carious lesions
its a ‘‘microbial indicator of disease state’’
normally spirochetes and fusiform bacilli live in the mouth flora, what happens in the case of fusospicrochetes
when there is bleeding in the oral cavity
the bacteria can cause infections and diseases to the oral cavity
what are the big 3 responsible for periodontisis
T. denticola
P. gingivalis
A. actino…mitans
features of treponema denticola
gram negative anaerobic
motlie
highly proteolytic
contributes to tissue degradation
features of porphyromonas gingivalis
gram-negative anaerobic
big factor for periodontitis in adults
produces alot of well known virulence factors
features of aggregatibacter actino…mitans
gram-negative facultative
non-motile
big factor in adolescent aggressive periodontitis and bone loss
outline the virulence factors of A. actino…mitans
leukotoxins - kills PNMs and monocytes
cytolethal distending toxin
immunosuppression factors - inhibit blastogenesis, antibody production and activates T-suppressors
what is interspecies bacterial cell-cell communication mediated by
dihydroxypentaedione (DPD)
autoinducer-2 (AI-2)
outline baterial intraspecies cell-cell communication and what does it lead to
gram positive bacteria produce small peptides such as: competence stimulating proteins
help promote single species biofilm formation
how can periodontal pathogens be prevented from joining the biofilm
attachment blockers
detachment signals
how does helicobacter pylori colonise the gut and what does it cause
penetrates mucin lining
then produces urease to neutralise stomach pH
causes - stomach ulcer and cancers
outline attachment of helicobacter pylori to the mucin lining and how it survives
survives in the very acidic environment by producing urease - converts urea into basics and buffers
cannot be killed by the immune system
outline the effect of toxin production of H. pylori
VacA kills cells in the lining of the stomach
decreases competition for nutrients for the bacteria
how does H. pylori protect itself from the host immune system
invade inner layer of the stomach lining to nest there
kills the cells they invade - creates holes
leads to formation of ulcers
functions of TlpA/D
TlpA/D - independent acid sensors
TlpD only - meditates attraction towards basic pH
function of omeprazole
blocks acid production
increases colonisation of glands
what can ureolytic activity cause
production of ammonia
when close to the gastric epithelium it causes cell damage and inflammation
difference between breast-fed and formular-fed babies in terms of gut flora
breast-fed - becomes dominated by bifidobacteria
formula - more diverse flora
what are the 3 types of enterotypes
type 1 - high levels of bacteriodes
type 2 - low levels of bacteriodes but prevotella are common
type 3 - high level of ruminococcus
what are the symbiotic benefits of the gut flora
ferment unused energy substrates
train immune system
prevent growth of pathogenic bacteria
regulate gut development
produce vitamins - biotin/vitamin K
produce hormones to store fats
function of pattern recognition receptors (PRR)
allow the intestine to distinguish between pathogenic and commensal bacteria
what are the 3 main immunosensory cells in the gut
surface enterocytes
M cells
dendritic cells
function of toll-like receptors (TLR) in the gut
help repair damage due to injury (via radiation)
what is nucleotide-binding oligomerisation domain/caspase recruitment domain isoform (NOD/CARD)
cytoplasmic proteins that respond to endogenous/microbial molecules or stress
forms oligomers that activate inflammatory caspase
what is the result of NOD/CARD performing their funtion
inflammatory caspase results in cleavage and subsequent activation of important cytokines and NF-kB signalling pathways
induces inflammatory response
what are capsular polysaccharides
polysaccharides that provide a mucous-like barrier for the bacteria on its surface
what do 2 of the 8 polysaccharides of capsular polysaccharides exhibit
a zwitterionic structure
(positive and negative charge on each sugar)
difference between T helper 1/2 cells
1 - activate cellular arm of the immune system - cytokines, killer T cells, macrophages
2 - activate humoral arm of the immune system - produces B cells
outline how the balance between Th1/2 cells can be achieved in germ-free mice
introduction of B. fragilis or PSA increased IFNγ to normal levels
reduced Th2 cytokine levels
what do Th17 cells produce
IL-17
potent inflammatory cytokine
implicated with every known autoimmune disease
