7/25/2019 B1 H pylori 2

1/13

.

7/25/2019 B1 H pylori 2

2/13

.7

7/25/2019 B1 H pylori 2

3/13

IL-8

Proteolyticenzymes

O 2 radicals

Infection with H. pylori results in anacute inflammatory reaction

Epithelial cell

Polymorph

7/25/2019 B1 H pylori 2

4/13

AntibodiesAntibodies

Monocytesand

lymphocytes

Evasion of the host chronic inflammatory reaction by H. pylori leads to chronic active gastritis

7/25/2019 B1 H pylori 2

5/13

7/25/2019 B1 H pylori 2

6/13

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

7/25/2019 B1 H pylori 2

7/13

7/25/2019 B1 H pylori 2

8/13

Gastric metaplasia

7/25/2019 B1 H pylori 2

9/13

Natural $istory o% H.pylori

S.Suerbaum. N E J M 2002

7/25/2019 B1 H pylori 2

10/13

.

x

7/25/2019 B1 H pylori 2

11/13

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

7/25/2019 B1 H pylori 2

12/13

. 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

7/25/2019 B1 H pylori 2

13/13

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