BMS2052 Study Guide - Final Guide: Helicobacter Pylori, Atrophic Gastritis, Peptic Ulcer
4 May 2018
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Helicobacter pylori
Causes chronic gastritis and peptic ulcer.
Increases risk of gastric cancer MALT
lymphoma B cells involved.
H.pylori only infects humans.
High acid: antral predominant, increased risk
of duodenal ulcer.
Low acid: pan gastritis all over, increased
risk of gastric cancer.
CLINICAL MANIFESTATION
Gastric cancer occurs in around 1% of
patients. There are pre-disposing factors such
as cag PAI and host factor IL-1B gene
polymorphism. There are two types of cancer.
Follicular gastritis MALT lymphoma (B-
cells) and atrophic gastritis intestinal
hyperplasia dysplasia gastric
adenocarcinoma.
Has Urease which catalyses the hydrolysis of
urea into carbonic acid and ammonia. Flagella
work with urease to get into the mucus.
H.pylori uses chemotaxis towards a high pH,
urea, bicarbonate and aa which are associated
with mucin.
CheA – kinase
CheY – reponse regulator which changes
direction of motor rotation.
TIpB – chemoreceptor – detects urea
These proteins are needed for colonisation.
ChA/Y KO mutant cannot colonise. TIpB
mutant can colonise but cannot persist.
Adhesins – to adhere to epithelial cells. These
are required for persistence. BabA (blood
group antigen binding adhesion) which binds
to surfaces of gastric epithelium - LeB. SabA
mediated binding to LeX antigen. These can
be switched on or off to allow bacteria to
dissociate itself from WBC.
OUTER MEMBRANE VESICLES
Have PG and Vacuolating cytotoxin A (VacA)
OMVs induce innate (NOD-1 – cytosolic PRR)
and adaptive IMM
OMVs can be secreted even when the
bacteria are not tightly adhered to the
epithelium.
VacA is a secreted toxin that forms oligomeric
structures that insert into the host
membrane. They are not encoded in the
CagPAI. There are two domains in each toxin
and S and M, eg S2 is not cytotoxic but
S1M1 is associated with carcinoma. When
VacA binds to the plasma membrane VacA
forms an anion-sensitive channel allow
water into cell. Notw that VacA can also:
casue cell damage, disrupt tight junctions,
block T cell response and serve as an ashesin.
Forms of diagnosis of H.pylori include urea
breath test, faecal antigen test, endoscopic
tests, histological test, urease based – CLO
test (yellow is negative, red is positive).
Treatment is with PPI and 2 antibiotics
(Amoxicillin and clarithromycin).
PATHOGENESIS
H.pylori strains with CAG PAI are more severe
– has T4SS, CagA and PG. They have the T4SS
in genome. T4SS allows entry of CagA and PG
into host cell. It binds with the CagL protein at
the top of the pilis to a5B1 integrin on the
host. Generally binds at lipid rafts.
CagA causes RAS-MEK pathway activation
apoptosis and abnormal cell growth. Also
causes cytoskeletal changes and cell motility
hummingbird phenotype. These cells are
pre-cancerous.
PG causes NOD-1 activation NF-kB which
causes IL-8 increase causes neutrophil
induction. Note that PG is also in OMVs.
Neutrophils IL-1B and TNF-a act on parietal
cells to decrease acidity (better conditions for
growth) can lead to gastric cancer
T4SS induces cell scattering in epithelial cells.
CagA can be phosphorylated.
Phosphorylated effects: eg by SARC kinase
then able to interact with host proteins such
as SHP-2. This increases proliferation and
Document Summary
Increases risk of gastric cancer malt lymphoma b cells involved. High acid: antral predominant, increased risk of duodenal ulcer. Low acid: pan gastritis all over, increased risk of gastric cancer. Gastric cancer occurs in around 1% of patients. There are pre-disposing factors such as cag pai and host factor il-1b gene polymorphism. Follicular gastritis malt lymphoma (b- cells) and atrophic gastritis intestinal hyperplasia dysplasia gastric adenocarcinoma. Has urease which catalyses the hydrolysis of urea into carbonic acid and ammonia. Flagella work with urease to get into the mucus. H. pylori uses chemotaxis towards a high ph, urea, bicarbonate and aa which are associated with mucin. Chey reponse regulator which changes direction of motor rotation. Baba (blood group antigen binding adhesion) which binds to surfaces of gastric epithelium - leb. These can be switched on or off to allow bacteria to dissociate itself from wbc. Omvs induce innate (nod-1 cytosolic prr) and adaptive imm.
