b1 h pylori 2
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IL-8
Proteolyticenzymes
O 2 radicals
Infection with H. pylori results in anacute inflammatory reaction
Epithelial cell
Polymorph
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AntibodiesAntibodies
Monocytesand
lymphocytes
Evasion of the host chronic inflammatory reaction by H. pylori leads to chronic active gastritis
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Dixon 199
Two major patterns of H. pylori gastritisPattern of Gastric Acid Duodenal Peptic ulcer
gastritis pathology output pathology risk
!astricmetaplasia
"cti#e c$ronicin%lammation
Duo&enal ulcer '$ronic in%lammation (olymorp$ acti#ity
'$ronic in%lammation (olymorp$ acti#ity "trop$y )ntestinal metaplasia
Normal !astric ulcer
Pan-gastritisPan-gastritis
Antr m-Antr m-predominantpredominant
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Gastric metaplasia
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Natural $istory o% H.pylori
S.Suerbaum. N E J M 2002
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Faktorchemotaxis monocyte
Gangguanmikrosirkuler
Cytotoxin
NH 3 UreaUreas
e
O 2O 2 -
MPO
H 2 O 2
HOCINH 2 CI
monochrolamine
NH 3
I -!
immunitas Com"lex
I - !
Neutro"hil
Mastsel
Ga ngguan#N$%
#N$ %
!.pylory - gastric m cosa in" ry
H.pylori
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. Figure 2 (facing page) !athogen"#ost Interactions in the !athogenesisof #elicobacter pylori Infection
The host response to # pylori participates in the induction of damage to the gastric epithelium and therefore has an integralrole in # pylori pathogenesis
$uring the early phase of the infection% binding of # pylori to gastric epithelial cells% in particular through &ab' and by strains harboring the cag pathogenicity island% results in the production ofinterleu in"*and other chemo ines% such as2 epithelial"cell"derived neutrophil"activating peptide +* (E,'"+*) and- growth"related oncogene a (./0"a)%
by epithelial cells
,uclear factor" & (,F" &) and the early response transcription"factor activator protein ('!" ) are the intracellular messengers involved in this process
The chemo ines secreted by epithelial cells bind to the proteoglycan scaffolding%generating a gradient along which polymorphonuclear cells (!1,) are recruited
The chronic phase of # pylori gastritisassociates an adaptive lymphocyte response with the initial innate response
ymphocyte recruitment is facilitated by chemo ine"mediated expression of vascular addressins such as 3vascular"cell adhesion molecule (45'1" ) and
2 intercellular adhesion molecule (I5'1" ) that are re6uired for lymphocyte extravasation
1acrophages that participate in interleu in"* production produce proinflammatory cyto ines involved in the activation of the recruited cells% in particular T helper cells (Th7% Th % Th2)% that respond with a biasedTh response to # pyloriIn turn% Th "type cyto ines such as interferon"g (I,F"g) induce the expression of class II major histocompatibility complexes(1#5) and accessory molecules &+" and &+"2 by epithelial cells% ma ing them competent for antigen presentation
The cytotoxin 4ac'" and Fas"mediated apoptosis induced by tumor necrosisfactor a (T,F"a) leads to disruption of the epithelial barrier% facilitating translocation of bacterial antigens and leading to further activation of macrophages 5yto ines
produced by macrophages can also alter the secretion of mucus% contributing to # pylori"mediated disruption of the mucous layer
5yto ines produced in the gastric mucosa induce changes in gastric acid secretion and homeostasis (dashed lines)
T,F"a% interleu in" b% and interferon"g increase gastrin release% stimulating parietaland enterochromaffin cells and thus acid secretionT,F"a also induces a decrease in the number of antral $ cells% leading to decreased somatostatin production and indirectly enhancing acid production
!8 denotes lipopolysaccharide
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Figure 1. The cag !athogenicity Island1ost H. pylori strains that cause disease (so"called type I
strains) contain the cag pathogenicity island% a chromosomalregion with about -+%777 bp and 29 genes% whose location isindicated by the arrowsThe figure shows the arrangement of genes in strain 2::9;%whose genome se6uence was the first to be published The island is split into two parts in some strains 1ost of thecag genes are probably involved in the assembly of secretorymachinery that translocates the protein 5ag' into thecytoplasm of gastric epithelial cellsFive genes (mar ed in orange) are similar to components of thetype I4 secretion system of the plant pathogen
Agrobacterium tumefaciens (4ir proteins)!roteins encoded by the island are involved in two major
processes% the induction of interleu in"* production by gastrice ithelial cells and the translocation of 5a ' from the