Inflammation of the intestinal mucosa caused by H. pylori

Faculté des Sciences de Tunis Département de Biologie

realized by: Draoui Jihéne Abdslem Ghayith Saidi Nasreddine:

Plan

The interface of the pathogen H.Pylori and the host immune system

The normal response of the mucosal immune

Ulcer disease

Immune effectors of the intestinal mucosa

Definition

Summary

Definition

Inflammation is the body reaction against injury or irritant is not synonym for infection. Only affects living tissue

Main Types of Inflammation:

Acute• Rapid onset and of

shorter duration

Chronic• Slowest onset with

protracted duration

Immune effectors of the intestinal mucosa

Epithelium: • enterocytes • Goblet cells • Paneth cells • Intra-Epithelial

Lymphocytes

Lamina propria: • CD4 + T / T CD8 + • Plasma IgA + • DC • macrophages • Innate Lymphoid cells

Peyer's patches: DC CD4 + T / T CD8 + B lymphocytes

Innate immunity non specific barrier:

Mucosal barrier: tight junctions

There are four major types of junctions in epithelial cells.

Some encircle the cell like a belt, attaching it to it's neighbors on all sides. Others are more like 'spot welds' that tie two cells together at a specific region or form a tunnel connecting the cytoplasm of adjacent cells.

Tight junctions also help to distinguish the apical and baso lateral domains of the cell by acting as intracellular barriers to macromolecules and proteins between these two regions

Globet cells mucin Paneth cells α-defensins

There are two types of α-defensins: DEFA5 and DEFA6 are expressed in Paneth cells of the small intestine, where they may regulate and maintain microbial balance in the intestinal lumen.

Mucin glycoproteins are thought to play an important role in protecting the intestine from chemical or physical injury but the mechanisms of protection and the possible relationship between mucin structure and function are incompletely understood.

Antigen presentation

dendritic cells "M" cells

IEL EnterocytesαEβ7 E-cadherin

Intra epithelial lymphocytes:T CD8 + αβ and γδ T

Strategically located to respond to antigenic stimulation

Most T-cells are CD8+

Mainly αβ TCR (In mice, γδ TCR predominates).

Innate Lymphoid CellsT γδ, iNKT, LTi-like, NKp46+…

Production of IL-17 and IL-22

Many studies have shown that γ δ T cells and the IL-17 that these cells produce are important in early defense against bacterial infection.

IL-17A and IL-17F play protective roles in host defense against certain pathogens at epithelial and mucosal barriers.

IL-22 is a member of the IL-10 cytokine family, described as having pro inflammatory activities on liver, pancreas, intestine and skin.

Lamina propria

Lymphocytes T CD4+Th17

Plasma IgA + CD4 + T lymphocytes

What Is an Ulcer?

An ulcer is a sore, which means it's an open, painful wound. Peptic ulcers are ulcers that form in the stomach or the upper part of the small intestine, called the duodenum. Peptic ulcers are actually very common.

What Causes an Ulcer?

In 1982, two doctors — Barry Marshall and Robin Warren — discovered a certain kind of bacteria that can live and grow in the stomach, Helicobacter pylori (or H. pylori)

The bacterium causes peptic ulcers by damaging the mucous coating that protects the stomach and duodenum.

Damage to the mucous coating allows powerful stomach acid to get through to the sensitive lining beneath.

The stomach acid and H. pylori irritate the lining of the stomach or duodenum and cause an ulcer.

Although H. pylori are responsible for most cases of peptic ulcers, these ulcers can happen for other reasons, too.

What are the symptoms of a peptic ulcer?

•Stomach pain is the most common symptom of an ulcer.•It usually feels like sharp aches between the breastbone and the belly button. •loss of appetite•nausea•burping •weight loss•vomiting •bloody or blackish bowel movements

Emergency Symptoms•sharp, sudden, persistent, and severe stomach pain•bloody or black stools•bloody vomit or vomit that looks like coffee grounds•bleeding—when acid or the peptic ulcer breaks a blood vessel•perforation—when the peptic ulcer burrows completely through the stomach or duodenal wall•obstruction—when the peptic ulcer blocks the path of food trying to leave the stomach

How Are Ulcers Diagnosed?

Blood test Urea breath test

Endoscopy Upper gastrointestinal (GI) series

Non invasive

Techniques

Invasive Techniques

In the absence of inflammatory stimuli, the normal response of the mucosal immune system to foreign antigens is tolerance

There are two possible and opposite outcomes of exposure to foreign antigens entering through the mucosa of the gut.

These are tolerance in the case of food antigens, which is contrasted with a vigorous antibody and T-cell response after exposure to pathogens.The essential difference between antigenic challenge by food compared with that by pathogens is that the pathogens cause inflammation, whereas food does not.

Both the antigens within food and the antigens within pathogens are presented by antigen presenting cells to T lymphocytes , but the contexts in which these two sources of antigen are presented are quite different.

Three different responses of T cells to the presentation of peptides derived from foods and other antigens delivered via the mucosa may account for the phenomenon of oral tolerance

The first is the deletion of antigen -specific T cells by the induction of apoptosis.

The second response is anergy, in which T cells presented with peptide in the absence of co-stimulatory signals become refractory to further stimulation with antigen

The third response involves the development of regulatory T cells , which can actively suppress antigen -specific responses following rechallenge with antigen.

1

2

3

The interface of the pathogen H.Pylori and the host immune system

H. pylori binds to gastric epithelial cells through BabA and other adhesins.

In strains that carry the Cag pathogenicity island (Cag-PAI), a type IV secretory apparatus allows translocation of effector molecules such as CagA into the host cell production of interleukin (IL)-8 and other chemokines by epithelial cells.

The secreted chemokines lead to the recruitment of polymorphonuclear cells (PMNs), resulting in inflammation.

CagA might cause disruption of the epithelial barrier and dysplastic alterations in epithelial-cell morphology.

Tumour-necrosis factor-alpha (TNF-alpha)-mediated apoptosis may also lead to disruption of the epithelial barrier.

The chronic phase of H. pylori Cytokines produced by macrophages, particularly IL-12, activate recruited cells such as helper T cells (TH0, TH1 and TH2) and B cells.

Cytokines also alter the secretion of mucus, which contributes to H. pylori-induced disruption of the mucous layer, as they induce changes in gastric-acid secretion and homeostasis.

H. pylori inhibits the host immune response by blocking the production of (NO) by macrophages and through the ability of VacA to interfere with the IL-2 signalling pathway in T cells by blocking transcription of the genes encoding IL-2 and IL-2R

1 2

3 4

5

6

6

The key distinction between tolerance and the development of

powerful protective adaptive immune responses is the context

in which peptide antigen is presented to T lymphocytes in the mucosal immune system.

Summary

Mucosal immune system needs to selectively respond to pathogens

Humoral immune response is IgA dominated.

Unique lymphocyte repertoire and cytokine environment limit inflammation

Thank you for your attention

references

• http://www.bio.davidson.edu/people/kabernd/berndcv/lab/epithelialinfoweb/Tight%20Junctions.html

• http://www.biocarta.com/Catalog.aspx?cid=35045&mid=-1• http://cochin.inserm.fr/Departements/ih/equipe-bomsel• http://sciencedesprobiotiques.ca/les-bacteries-et-votre-sante/systeme-de-defense-de-l

organisme/les-trois-lignes-de-defense/• http://blog.therabreath.com/tag/helicobacter-pylori/• https://microbewiki.kenyon.edu/index.php/Gastritis_and_Peptic_Ulcer_Disease_Cause

d_by_Helicobacter_pylori• http://www.nature.com/nrmicro/journal/v2/n9/fig_tab/nrmicro955_F3.html• http://www.nature.com/nrm/journal/v2/n6/fig_tab/nrm0601_457a_F1.html• http://www.nature.com/mi/journal/v5/n1/full/mi201155a.html• http://www.ncbi.nlm.nih.gov/books/NBK27169/• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/I/Inflammation.html