2/27: mucosal surfaces, enterobacteriaceae-diarrheal diseases Flashcards
Name 3 members of the enterobacteriaceae family that cause diarrhea
- e. coli
- salmonella species
- shigella species
Mucosal surface definition and examples
any surface that interacts with air and has glands that secrete mucous
examples: oral cavity, respiratory tract, repro/urinary tract, GI
What are the defenses of mucosal surfaces?
innate immunity, adaptive immunity and non-specific barriers (the cells themselves, mucous are physical barriers against infection)
E. Coli 0104:H4 OUtbreak
caused by ____
3500 causes, 800 caused by ____
32 people died, surprising because ____
caused by alfalfa sprouts, cucumbers
800 cases associated with hemolytic uremic syndrome
32 death is surpsing because this is rare for e. coli infections
E. Coli 0:26 outbreak
caused by ____
produced ____ (associated with bloody diarrhea)
mortality?
caused by chipotle
produced shiga toxin (associated w/ bloody diarrhea)
50 cases, half hospitalized, nobody died
Why do oral healthcare practitioners care about GI diseases?
they originate in the ORAL CAVITY due to fecal matter contamination
How does it get there? 7 F’s
What are the 7F’s?
how fecal matter contamination enters the oral cavity
feces food fluids fingers fomites fornication
What is an inoculum size?
Low inoculum size range? spread by?
high inoculum size range? spread by?
inoculum size = amount of bacteria it takes to make someone sick (ID, infectious dose)
low ID: 50-100, usually spread by fomites or fingers so it doesn’t take as much
high ID: require millions of organisms to cause disease, so you would need bacteria to be in your food/drink
Name the 5 natural barrier defenses of the GI system
- natural anatomical and physiological properties
- acidity (and change in acidity) (stomach = 1-2, duodenum = 9)
- motility (chime moves through stomach and small intestine quickly, so bacteria need to be able to directly adhere to epithelium or mucous layer)
- mucous layer
- tight junctions hold epithelial cells together, prevent penetration of bacteria
normal flora in GI provides a physical barrier by ____
competing with pathogens for nutrients and oxygen
Name the 6 secretory antimicrobial compounds found in the GI system
- lysozymes
- lactoferrin
- cathelicidin
- alpha defensins
- beta defensins
- secretory Igs
Describe how lysozymes defend against bacterial invasion of GI tract
cleaves NAG and NAM linkage (although the murein isn’t directly exposed in gram Negs it still works)
Describe how lactoferrin defend against bacterial invasion of GI tract
sequesters/hides iron from bacteria
Describe how cathelicidin defend against bacterial invasion of GI tract
disrupts gram pos and gram neg membranes
Describe how alpha defensins defend against bacterial invasion of GI tract
made by ____
create pores in microbes
made by neutrophils and intestinal paneth cells
Describe how beta defensins defend against bacterial invasion of GI tract
made by ____
creates pores in microbes
made by epithelial cells
Describe how Igs defend against bacterial invasion of GI tract
secretes IgA specifically
What are the 3 ways that pathogenic bacteria overcome the innate barrier defenses of GI tract?
- acid resistance
- fimbriae/pilli
- bacterial structures
how does acid resistance help bacteria overcome innate barrier defenses in GI?
how does ID # play a role?
just enough acid resistance to get them through the stomach and into duodenum
microbes with low ID tend to be more acid resistant
How do fimbriae/pilli help bacteria overcome innate barrier defenses in GI?
helps microbe adhere to tissues
How do bacterial structures help bacteria overcome innate barrier defenses in GI?
bacteria can slightly change their cell membranes to evade bactericidal compounds, can incorporate cationic amino acids into cell membrane to reduce effect of cationic antimicrobial peptides
can sequester iron through siderophores
Macrophages are important for mucosa immunity because they recognize _____
TLR4 recognizes ____
macrophages recognize PAMPs and activate and kill many of the microbes
TLR4 recognizes LPS of gram negative bacteria
Describe the enteroibacteriaceae family general info
gram negative
range from coccobacilli to elongated rods
facultative aerobes
don’t form spores
ALL HAVE ENDOTOXIN LPS, some produce and secrete exotoxin
Enterobacteriaceae family all have cell wall components that are antigenic. 3 main types:
- O antigen (outer antigen, LPS)
- K antigen (polysaccharide capsule, not all have)
- H antigen (flagella)
What is a serotype?
Define e.coli O157:H7
variations within a bacterial species due to the difference in cell wall surface antigens
e.coli O157:H7 mean O-antigen LPS is type 157 and H-antigen flagella is type 7
Escherichia coli
most ferment ___
and produce ___
ferment lactose
produce indole
Escherichia coli serotypes are determined by ___ antigens
O, K, H
Most common type of pili on escherichia coli is ____
type 1
Type 1 pili on escherichia coli binds ____
d-mannose on epithelial cells
this has an on/off switch that turns ON in presence of ACID
The p pili on escherichia coli binds ____
digalactoside in urinary tract and in some erythrocytes
Other pili (not type 1 or p pili) on escherichia coli are common to _____ and bind to ____
common to diarheal strains
bind enterocytes
What are the 3 main toxins associated with scherichia coli?
- alpha-hemolysin
- CNF (cytotoxic necrotizing factor)
- shiga toxin
Alpha-hemolysin toxin of e.coli forms ___
pores
CNF (cytotoxic necrotizing factor) toxin of e.coli does what?
a-b toxin
produces g proteins
disrupts intracellular signaling
Shiga toxin of e.coli does what?
a-b toxin
blocks protein synthesis by modifying ribosomes
“Pathogenic e. coli is SELF LIMITING”
what does this mean?
bacteria are being flushed out and cell turnover is very high in the colon
so anything tha tattahces will be gone soon
What are exceptions to “pathogenic e. coli is self limiting”
EAEC = diarhea for weeks
EPEC = can be chronic
EHEC and EIEC = bloody diarhea bc shiga toxin
EPEC (enteropathogenic e. coli)
has ___ ID
causes ___
outbreaks occur in _____
high ID
affects SMALL INTESTINE
outbreaks in nurserys and developing countries
What are the pili for EPEC (enteropathogenic e.coli)
Bfp (bundle-forming pili)
adheres to distal small intestine enterocytes
EPEC (enteropathogenic e.coli) uses ___ secretion system
type III
injects e.coli secretion proteins into host cell
EPEC (enteropathogenic e.coli) uses specific protein intimin-Tir
What does this do?
it is injected into the cell, goes to the membrane and allows bacteria to attach to the cell
this facilitates actin polymerization to form a “pedestal” for the bacteria to sit in
What toxin does EPEC produce?
none.
doesn’t invade = doesn’t produce toxin
EPEC likely causes diarrhea due to ____
defacement of microvili and tight junctions
EHEC (enterohemerrhagic e.coli) has \_\_\_ ID causes \_\_\_ \_\_\_ toxin occurs in \_\_\_
low id shiga toxin causes bloody diarrhea occurs in developed countries comes from animal products or vegetables/fruits due to cow manure fetilizer
EHEC has shiga toxin which produces bloody diarrhea.
This can lead to _____
hemolytic uremic syndrome
EIEC (enteroinvasive e.coli) is similar to ____ infection
similar to shigella infections
causes milder form of shigellosis
EIEC (enteroinvasive e.coli) is acquired through ____
contaminated food/water
humans are the only reservoir
EIEC (enteroinvasive e.coli) attaches to the host cell and…..
evades the endosome
multiplies inside cytoplasm
uses host cell actin to push through neighboring cells
EAEC (enteroaggregative e.coli) leads to ____ that lasts ____
watery diarrhea that lasts up to 2 weeks
involved tight adherence of bacteria to epithelial cells in “stacked brick pattern”
E.coli o104:h7 was which strain of e.coli?
eaec
What is shigella?
specialized e.coli that only has O and K antigens
because no H antigen = no flagella (non motile)
All species of shigalla are einvasive and multiply within ___
epithelial cells
Do all forms of shigella produce the shiga toxin?
no
What are the 4 species of shigella?
shigella dysenteriae - type 1, most serious, bloody diarrhea
shigella flexner - most common
shigella boydii
shigella sonnei - common, no bloody diarrhea
Shigellosis
strictly infects ___
__ ID
___ resistant
strictly infects humans
ID = 10 low
acid resistant
Shigellosis pathogenesis:
attaches to __ cells via ___
attaches to M cells via Ipa (invasion plasmid antigens)
Shigellosis pathogenesis
Where in an M cell is it going to invade?
after shigella escapes the phagosome, it kills the macrophage.
now it can get to the LAMINA PROPRIA
Shigellosis uses ___ secretion system
this helps inject ____ into what part of an enterocyte?
type III
helps inject IpaA and IpaD into BASOLATERAL SURFACE OF ENTEROCYTE
Shigella injects IpaA and IpaD into ____ of enterocyte
basolateral surface of enterocyte
How does shigella get from the basolateral surface of enterocyte into the enterocyte?
it properls itself into the enterocyte using host cytoskeletal rearrangement
Once inside the enterocyte, how does shigella move around?
because no h antigen = no flagella = non motile
moves around using HOST ACTIN
When shigella-invaded cells die and are sloughed off, what hapepns?
ulcer is formed at site of enterocyte death
diarrhea results from infalmmation
presents as CLASSIC DYSTENTERY (small volume diarrhea + leukocytes + RBC)
Immunity against shigellosis?
produces antibodies
not protective over other serotypes
How do you diagnose shigellosis?
stool culture or O-antigen agglutination
Salmonella typhimurium causes ___
ID _____
acquired from ____
gastroenteritis
ID ranges from high to low
acquired from egg/poultry dishes
Which is more acid sensitive: shigella or salmonella?
salmonella
T/F: Salmonella typhimurium is transmitted via fecal-oral transmission from human to human
false
fecal-oral transmission from huamnd or animals
Salmonella typhimurium bacteria attaches to ___ cells
uses ___ secretion system to inject proteins into host
M cell
Type III secretion system
Salmonella typhimurium bacteria causes a ___ apperance of host cell
ruffled
as it uptakes the bacteria
Salmonella typhimurium bacteria remains in the host cell to multiply for hours.
it is then released into the ____, stimulating a ____ response
lamina propria
stimulating an inflammatory response
bacteria is then taken up by phagocytes (mostly macrophages)
If salmonella typhimurium escapes phagocytosis in the lamina propria, what does it do?
causes bacteremia
T/F salmonella typhi is strictly human pathogen that can have asymptomatic carriers
true
Where do salmonella typhi multiply?
how?
in macrophages
by inhibiting oxidative bursts
What immune response oes salmonella typhi cause?
th1 and th2
diagnosis of salmonella typhi?
stool sample or blood
to identify the O serogroup