Exam 3: Respiratory Viruses and Bacteria Flashcards
consists of ciliated epithelial cells, goblet cells, and dendritic cells
conducting airway
- move bad things out
- synthesize antimicrobial peptides
ciliated epithelial cells
produce mucus (protein called mucin with polysaccharide modification)
goblet cells
- hydrophilic
- keep epithelia hydrated
- made by goblet cells
mucin
what are the different types of mucin?
- membrane anchored mucin
- polysaccharide secreted mucin
- intraepithelia
- carry out surveillance
dendritic cells
consists of type 1 epithelial cells, type 2 epithelial cells, and macrophages
alveoli
- thin for gas exchange
- provide the most coverage
type 1 epithelial cells
- rounded
- produce surfactant
type 2 epithelial cells
- made by type 2 epithelial cells
- protein + lipids
- attached or secreted
surfactant
- carry out antigen presentation
- phagocytosis to keep airway clear
alveolar macrophages
love the lipids in the airway
mycobacterium tuberculosis
how do the lungs of germ free mice compare to conventional mice?
have less mature alveoli
what happens if you give germ free mice Lactobacillus into the nose?
- develop normal lungs and normal # of alveoli
- having bacteria in lungs helps develop structure
what happens during the flu in relation to resistance against bacterial infections?
decrease resistance against bacterial infections during flu
naked virus
non-enveloped virus
virus enclosed in membrane
enveloped virus
naked RNA of virus
icosahedron
*picornarvirus
~ssRNA
~icosahedron
rhinovirus
coronavirus
SARS (severe acute respiratory syndrome)
paramyxovirus
RSV (respiratory synctial virus)
involves replication of genome and proteins
virus replication
what are the steps of virus replication?
- attachment to host receptor
- entry (at least genome)
- synthesis - genome replicates and viral protein synthesis in host (in cytosol)
- assembly of stuff that was synthesized
- assembled virus particle needs to be released
virus particle with all its parts
virion
- goes from upper respiratory tract to lower tract
- icosahedral capsid
- +ssRNA
- naked
- positive sense
- cellular tropism = respiratory epithelial cells
rhinovirus
what are the host receptors on respiratory epithelial cells that rhinovirus binds to?
- ICAM-1 (intercellular adhesion molecule)
- LDLR (low density lipoprotein receptor)
increases during inflammation
ICAM-1
viral ligands of rhinovirus that bind receptors
-capsid proteins
~VP 1/2/3
- conducting airways—>alveoli
- pleomorphic
- -ssRNA
- enveloped
- tropism = ciliated epithelial cells
RSV (respiratory synctial virus)
what is the host receptor for RSV?
CX3CR1 (chemokine receptor)
what are the viral ligands for RSV?
-surface G & F proteins
~surface glycoproteins
- in alveoli
- coronavirus
- pleomorphic/spherical
- +ssRNA
- enveloped
- tropism = pneumocytes (type 1 & 2 epithelial cells)
SARS (severe acute respiratory syndrome)
what is the host receptor for SARS?
ACE-1 (angiotensin converting enzyme 1)
-secretes ADH
what is the viral ligand for SARS?
spike protein(s)
what is the life cycle of rhinovirus?
- receptor binding to viral ligand
- receptor mediated endocytosis
- endosome (decreased pH)
- endosome releases +ssRNA into host
- can be used directly for protein synthesis (-RNA–> +RNA)
- +ssRNA goes to ribosomes on rough ER
- viral proteins and +RNA join in virus in cell
- cell lysis to release virions
what is the life cycle of RSV?
- G & F viral ligands bind with host cell receptor
- membrane fusion
- -ssRNA can’t be used for translation directly
- makes +RNA—> -RNA
- +RNA goes to rough ER which results in viral proteins
- viral proteins and -RNA in capsid
- viral proteins go to cell surface
- budding
what is the life cycle of SARS?
- ligand binds host cell receptor
- receptor mediated endocytosis
- endosome (decreased pH)
- membrane fusion —> release +RNA
- makes -RNA—-> +RNA
- +RNA goes to rough ER —> viral proteins
- viral proteins and +RNA join in endosome
- exocytosis
where is an infection most dangerous?
alveoli because there is no cilia
- enzyme that changes +RNA–>-RNA–>+RNA
- error prone~no proofreading
- antigenic diversity due to errors
RNA dependent RNA polymerase
how do infected epithelial cells start the immune response?
- induce apoptosis
- inflammation
- type 1 interferon response
- gram +
- catalase -
- beta hemolysis
- found on skin
- aerotolerant
- bacitracin sensitive
- have capsule
- have pili
- have hemolysin
- M protein (surface)
Group A strep (Streptococcus pyogenes)
what can kill Streptococcus pyogenes?
*Bacitracin (bacitracin test–>antibiotic)
what is the capsule of Streptococcus pyogenes made of?
hyaluronic acids
what hemolysin does Streptococcus pyogenes have?
streptolysin S and O
- facultative anaerobe
- beta hemolysis- beta hemolysin
- bacitracin resistant
- found in intestine or vaginal tract
- have capsule
- pili
- HvgA (hyper virulent GBS adhesin)
Group B strep (Streptococcus agalactiae)
what is the capsule of Streptococcus agalactiae made of?
sialic acid
- alpha hemolysis
- causes pneumonia
- found in nasopharynx
- facultative anaerobe
- have capsule
- pili
- hemolysin
- phosphororylcholine teichoic acid
Streptococcus pneumoniae
what is the capsule of Streptococcus pneumoniae made of?
- polysaccharide
- composition gives rise to serotypes
what is the hemolysin of Streptococcus pneumoniae?
pneumolysin
what do capsules play a role in?
- opsonization
2. phagocytosis
what do pili play a role in?
- attachment
2. adherence
what do hemolysins produce?
pore forming toxins (proteins)
what does the capsule of Group A strep inhibit?
- inhibits phagocytosis
- avoids recognition by own cells
what does streptolysin S and O of Group A strep lead to?
- damage
- inflammation, invasion, spread
- strep throat or skin infection
what does the pyrogenic exotoxin (super antigen) of Group A strep cause?
toxic shock syndrome (scarlet fever)
what does the M protein of Group A strep result in?
- adhesion
- epitopes mimic our self epitopes
-autoimmune diseases - antibodies and T cells recognize/against M proteins
-cross reactivity with myosin, sarcolemma membrane, neuronal gangliosides
~arthritis, carditis, rheumatic fever, sydenham chorea, kidney failure
what happens if a virulence factor of Group A strep is lost?
it may become less virulent and require more LD 50
- a virulence factor that can be produced by certain species of Streptococcus
- help them gain entry into a host by counteracting the host’s defences
- Group A strep
M protein
what are the steps of Group B strep invasion?
- intestines/vaginal tract
- cross mucosal barrier
- evade immune defenses
- cross blood-brain barrier
how does Group B strep cross the mucosal barrier?
- adhesins - pili
- paracellular translocation
- tight junctions
- hemolysin transcellular translocation?
How does Group B strep evade immune defenses?
- capsules
- degrade complement proteins
- bind Ig at fc
- D-ala (+) modification to teichoic acids
- inhibit AMP?
- superoxide dismutase inhibits ROS?
what happens when Group B strep crosses the blood-brain barrier?
- meningitis
- beta hemolysin and HvgA (adhesin binds to host receptor)
-leads to neurotropism
~microvascular endothelium
caused by Group B strep, Listeria monocytogenes
infant meningitis
caused by neisseria meningitis and/or streptococcus pneumoniae
older kids/adult meningitis
what is the path of Streptococcal pneumoniae?
- upper respiratory tract (asymptomatic carrier)
- lower respiratory tract
- alveoli
- blood
- brain
disease caused when streptococcal pneumoniae reaches the alveoli
pneumonia (liquid in lungs)
disease caused when streptococcal pneumoniae reaches the brain
meningitis
what doe streptococcal pneumoniae use to infect host?
- neuraminidase
- adhesins
- pneumolysin
- streptococcal pyruvate oxidase
- capsule
cleaves glycoconjugates on mucin ~ breaks mucosal barrier
neuraminidase (of Streptococcal pneumoniae)
adhesins that streptococcal pneumoniae use to attach to epithelium
pili
-form pores on epithelial cells
~inflammation
-inhibit mucocilliary action
pneumolysin of streptococcal pneumoniae
synthesizes hydrogen peroxide (H2O2)
streptococcal pyruvate oxidase
- PC-teichoic acid
- taken up by endothelium and dump at other side?
capsule
- aerobic
- rod-shaped
- high GC content
- Gram +
- phylogeny = actinobacterium
- very fatty bacterium
- has peptidoglycan layer and phospholipid
- mycolic acid
- slow grower
- classical intracellular pathogen
- hard to find/diagnose
mycobacterium tuberculosis
what percent of mycobaterium tuberculosis’ genome is dedicated to fatty acid synthesis or rmetabolism?
30%
what percent of mycobacterium tuberculosis’ dry weight is lipids?
40%
in an ideal lab condition what is the doubling time for mycobaterium tuberculosis?
15 hours
how is mycobacterium tuberculosis treated with antibiotics?
- long term antibiotic treatment
- bacteria needs to grow for abx to work
- abx sensitivity decreases if m. tuberculosis is not growing
what types of resistance does m. tuberculosis have?
- phenotypic resistance
- genetic resistance
- horizontal gene transfer is rare
- genome mutations for most part
cellular tropism is alveolar macrophages - likes to grow in host cell
mycobacterium tuberculosis
how does mycobacterium affect immune system?
-once infection happens, it elicits immune response
~disease/damage caused by immune response
what are the common tests to diagnose mycobacterium tuberculosis?
- TB skin test
2. Blood test
involves a skin injection with tuberculin(protein extract of Mtb), which serves as an antigen
TB skin test
what is the infection process for TB?
1.primary infection
-innate immune response
~clearance OR adaptive immne response
2. secondary infection
-adaptive immune response (t and b cells)
~clearance OR active TB (disease/infectious) OR granuloma latent infection
3. granuloma latent infection
-active TB OR clearance
how does granuloma latent infection trigger active TB?
- trriggers weakened immune defense
- steroids
- age
- malnutrition
- HIV~ comprimises T cell response
what is the result for TB test during primary infection?
negative skin test
what is the result for TB test during secondary infection or adative immune response?
positive skin test
- model environmental opportunistic pathogen
- very good at adapting to its environment
- 3 kinds of motility
- have capsules
- make different pigments depending on conditions
- priority 1 (critical) for WHO priority pathogen list for R+D of new antibiotics
Pseudomonas aeuroginosa
what are the 3 types of motility of Pseudomonas aeuroginosa?
- swimming (flagella)
- twitching (type 4 pili)
- swarming (flagella + pili)
what the capsules of Pseudomonas aeuroginosa like?
-form mucoid colonies
~polysaccharide capsule
-avoid immune recognition
produced by Pseudomonas aeuroginosa in low phosphorus conditions
pyocyanin (green)
produced by Pseudomonas aeuroginosa in ample phosphorus conditions and it is fluorescent
pyoverdin (green/yellow)
what is the pathogenesis process for Pseudomonas aeuroginosa?
- adhesion
- damage
- immune recognition
- biofilm composition
- antibiotic resistance ~ mcr-1 inhibits colistin
what does Pseudomonas aeuroginosa use for adhesion?
-LasA protease
-elastase protease
~both proteases degrade proteins of extracellular matrix
-flagella and type 4 pili to bind to cell surface
what does Pseudomonas aeuroginosa use to cause damage?
- pyocyanin
- ExoU
- ExoS
-causes oxidative damage
-secretes exotoxin A
~inhibits translation
~uses type 3 secretion to get protein into cytosol of host cell
pyocyanin of Pseudomonas aeuroginosa
phospholipase that degrades membrane
ExoU of Pseudomonas aeuroginosa
enzyme that adds ADP to RAS that results in disruption of actin cytoskeleton
ExoS of Pseudomonas aeuroginosa
what is involved in immune recognition of Pseudomonas aeuroginosa?
-toll like receptor 5 that recognizes flagellum
-LPS in outer membrane recognized by TLR4
~both lead to inflammation
how is the biofilm of Pseudomonas aeuroginosa formed?
-goes from planktonic (moving) to sessile
~builds biofilm structure
-cells stick together through extracellular polysaccharides
what are the extracellular polysaccharides that help cells stick together to form biofilm?
- Psl
- Pel
- Alginate
what else is in biofilm that helps cells stick together?
DNA
- helps resist antibiotics
- creates gradient
biofilm
what are the different sides of the gradient like formed by biofilms?
- metabolic processes occur outside the gradient
- on the inside there is low metabolic and respiratory activity
how do Pseudomonas aeuroginosa resist abx?
- modify gyrase + tophomerase to inhibit fluoroquinolones
- enzymes degrade abx
- eflux pump to transport abx out of cell
- outermembrane proteins stop expression of abx or cause mutations
-inhibits colistin
-adds phosphoethanolamine to lipid A
~modifies charge and substrate so it can no longer bind
mcr-1
MDR
multidrug resistance
HIV
human immunodeficiency virus
- genus=lentivirus
- enveloped
- 2 copies of ssRNA
- 9 genes~18 proteins
HIV
how are there 9 genes but 18 proteins for HIV?
-overlapping open reading frames
~forms polyproteins –> cleaved by both host and viral proteases to functional proteins
what are the genes of HIV?
- Gag
- pol
- env
- rev
- vif
- Vpr
- tat
- Vpu
- net
all 3 genes together make polyprotein
- Gag
- pol
- env
encodes core structural proteins
Gag
encodes integrase, protease, reverse transcriptase
pol
encode glycoproteins on envelope (gp120 & gp41)
env
what are the targets of HIV?
- macrophages CD4 and CCR5
- net protein down regulates MHC
- super infection
what happens if reverse transcriptase makes a mistake?
*mutations
-GP120 binds Cd4 and CXCR5 instead of CCR5
~called type switching
~new target is CD4+ T cells
why is HIV a superinfection?
- same person can have multiple versions of HIV
- mutation rate in HIV is much faster than adaptive immune response
- first stage of HIV infection
- weeks
-acute infection
- provirus
- need drugs during this stage to inhibit integrase and reverse transcriptase
latent infection
- final stage
- 0-3 years till the end of life
AIDS
- gram -
- Neisseria gonorrhoeae
- inner and outer membrane, lipooligosaccharides (LOS)
- facultative anaerobe
gonorrhea
- weak outside of host
- sensitive to environmental stresses
- humans are reservoirs
gonorrhea
how does gonorrhea infect a host?
-attach to vaginal or urethral epithelium
~surface proteins
~type 4 pili (twitching)
~LOS
how does gonorrhea evade immune defenses?
- *antigenic variation
- gene assortment/recombination
- phase variation
always modifying whats on the outside
antigenic variation of gonorrhea
expression of protein is sometimes on or sometimes off
phase variation
- caused by Treponema pallidum
- gram -
- spirochete
- no oxidative phosphorylation, no electron transport chain, no TCA cycle, no LPS
- small genome
- spread by sex
syphilis
what is the progression of syphilis?
sex–> primary syphilis (mild symptoms)–>secondary syphilis (treponema spreads) –>latent syphilis (3-30 yrs)–>tertiary syphilis (death)
serotype is a classification scheme defined by…..?
host immune response
true or false: all human pathogens grow best at human body temperature of 37 degrees celsius
false
what is the most ideal host to demonstrate rhinovirus as the causative agent of respiratory infections?
epithelial cells derived from lung tissues
true or false: a person with rhinovirus may still be contagious after his/her symptoms are gone
true
true or false: the main cause of symptoms in respiratory viral infections is immunopathological
true
what is the main reason why it is hard to develop a RSV vaccine?
immune immaturity of the target population
what specific step in viral replication does the drug Palivizumab block?
adhesion and entry
causes strep throat
Streptococcus pyogenes
causes rheumatic fever
cross-reacting antibodies
true or false: The LD50 for encapsulated Streptococcus pneumoniae is higher than non-capsulated Streptococcus penumoniae.
false
non-sporulating
Streptococcus pneumoniae
Beta-hemolytic
Streptococcus pyogenes
true or false: Mycobacterium tuberculosis had two phospholipid bilayer membranes
false
The host tropism of Mycobacterium tuberculosis is…
alveolar macrophages
does NOT exhibit rapid onset of symptoms
tuberculosis
- contained by cell-mediated immunity
- can be treated with antibiotics
- transmitted through respiratory route
tuberculosis
true or false: Tuberculosis can be effectively treated with a 2-week course of antibiotics
false
true or false: Mycobacterium tuberculosis without mycolic acids will have a higher LD50 value than Mycobacterium tuberculosis with mycolic acids
true
uses swimming, twitching and swarming motility
Pseudomonas aeruginosa
true or false: The only route of transmission for Pseudomonas aeruginosa is through inhalation of contaminated water droplets
false
- It is recognized by TLR4 on host cells
- It can facilitate interactions with CFTR on host epithelial cells
- It is a structural component of Gram negative bacteria outer membrane
LPS
true or false: Type three secretion system transports proteins from bacterial cytoplasm to the host cytoplasm.
true
Which of the following are SECRETED PROTEINS from Pseudomonas aeruginosa?
- elastase
- phospholipase C
an intracellular pathogen
HIV
when HIV is inserted into a host chromosome, it is called a….
provirus
For people with a mutated version of CCR5 that doesn’t bind to GP120, what would the LD50 for HIV be?
Higher than LD50 in people with wildtype copy of CCR5
true or false: People who die from AIDS are dying from secondary infections or cancer, not directly from HIV.
true
the bacterium that causes the sexually transmitted disease gonorrhea
Neisseria gonorrhoeae
Syphilis is caused by the bacterium…..?
Treponema (genus) pallidum (species)
