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H. p y l o r i

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R.P. H.Logan. BMJ 20

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.

H e l i c o b a c t e r p y l o r i

T.Yamada; Textbook of Gastroenterology 3rdEdition

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Helicobacter pylori (electronmicroscope)

.

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R.P.H.Logan. BMJ 200

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Urea breath tests (C13 and C14)

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A.J.Wood. EJ! "##$

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H.pylori - F r e e r a d i c a l s

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.

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.7

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IL-8

Proteolytic

enzymes

O2radicals

Infection withH. pylori results in anacute inflammatory reaction

Epitelial cell

Polymorp

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!ntibodies!ntibodies

"onocytesand

lympocytes

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

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Helicobacter pylori % g a s t r i c m & c o s a

'.'&erba&m. E J ! ())(

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Two major patterns ofH. pylori gastritisPattern of Gastric Acid Duodenal Peptic ulcer

gastritis pathology output pathology risk

Gastric

metaplasia

Acti,e c-ronic

inflammation

*&odenal &lcer -ronic inflammation

/olymorp- acti,ity

-ronic inflammation

/olymorp- acti,ity

Atrop-y

0ntestinal metaplasia

ormal Gastric &lcer

Pan-#astritisPan-#astritis

!ntr$m-!ntr$m-predominantpredominant

A l ( B) i i

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Antral (type B) gastritis

G t i t l i

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Gastric metaplasia

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at&ral -istory of H.pylori

'.'&erba&m. E J ! ())(

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Faktorchemotaxis monocyte

Gangguanmikrosirkuler

Cytotoxin

NH3 Urea

Urease

O2O2

-

MP

O

H2O2

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H.pylory - #astric m$cosa in%$ry

H.pylori

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. Figure 2 (facing page). athogen!"ost Interactions in the athogenesis

of "elicobacter pylori Infection.

The host response to ". pylori participates in the induction of damage to the gastric epithelium and therefore has an integral

role 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 of

interleuin!

and other chemoines$ such as

2. epithelial!cell!derived neutrophil!activating peptide * (E+&!*) and

,. growth!related oncogene a (-/!a)$

by epithelial cells.

+uclear factor!% (+F!%) and the early response transcription!factor activator protein ' (&!') are the intracellular messengers involved in this process.

The chemoines secreted by epithelial cells bind to the proteoglycan scaffolding$

generating a gradient along which polymorphonuclear cells (0+) are recruited.

The chronic phase of ". pylori gastritis

associates an adaptive lymphocyte response with the initial innate response.

1ymphocyte recruitment is facilitated by chemoine!mediated epression of vascular addressins such as 3

'.vascular!cell adhesion molecule ' (45&0!') and

2.intercellular adhesion molecule ' (I5&0!') that are re6uired for lymphocyte etravasation.

0acrophages that participate in interleuin!

production produce proinflammatory cytoines involved in the activation of the recruited cells$ in particular T helper cells (Th7$ Th'$ Th2)$ that respond with a biased

Th' response to ". pylori.

In turn$ Th'!type cytoines such as interferon!g (I+F!g) induce the epression of class II major histocompatibility complees

(0"5) and accessory molecules %*!' and %*!2 by epithelial cells$ maing them competent for antigen presentation.The cytotoin 4ac&! and Fas!mediated apoptosis induced by tumor necrosis

factor a (T+F!a) leads to disruption of the epithelial barrier$ facilitating translocation of bacterial antigens and leading to further activation of macrophages. 5ytoines

produced by macrophages can also alter the secretion of mucus$ contributing to ". pylori!mediated disruption of the mucous layer.

5ytoines produced in the gastric mucosa induce changes in gastric acid secretion and homeostasis (dashed lines).

T+F!a$ interleuin!'b$ and interferon!g increase gastrin release$ stimulating parietal

and enterochromaffin cells and thus acid secretion.

T+F!a also induces a decrease in the number of antral # cells$ leading to decreased somatostatin production and indirectly enhancing acid production.

18 denotes lipopolysaccharide.

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Figure 1. The cag athogenicity Island.0ost H. pylori strains that cause disease (so!called type I

strains) contain the cagpathogenicity island$ a chromosomalregion with about ,*$777 bp and 29 genes$ whose location is

indicated by the arrows.

The 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. 0ost of the

cag genes are probably involved in the assembly of secretorymachinery that translocates the protein 5ag& into the

cytoplasm of gastric epithelial cells.

Five genes (mared 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 interleuin! production by gastrice itheli l ell d the t l ti f 5 & f the