Lecture 4 - Infection - Helicobacter pylori Flashcards by Eleanor Nicklason

What are the main mechanisms of infectious agents causing disease?

Entry
Toxins:
• exotoxin
• endotoxin
• enzymes
Immunopathology

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How big are bacteria?

Generally

1-15 microns

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What are the various organisms that can cause disease in human hosts?

Bacteria
Viruses
Fungi
Parasites
(prions)

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What are the ‘non sterile’ areas on our body?

What does this mean?

Our body is largely colonised by micro-organisms
This is our microflora
 • skin
 • gut
 • mouth
 • nose
 • vagina

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Under which circumstances will microflora cause disease?

Antibiotic use wipes out microflora, pathogens can now colonise
immunocompromise
damage to barriers

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What factors determine virulence?

virulence factors
ability to evade immune system
ability to spread

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What are some barriers to infection?

Mechanical:
 • epithelium
 • flushing (urine, tears)
 • mucociliary elevator
Chemical:
 • lysozyme
 • phospholipase
 • pH
 • surfactant
 • mucous
Normal flora
 • occupying the niche

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What are the various sections of the stomach?

Cardia
Fundus
Corpus
Antrum

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What is the function of the cardia of the stomach?

Mucous secreting cells

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What is the function of the fundus of the stomach?

Acid and enzyme secretion

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What is the function of the corpus of the stomach?

Why is this significant? Explain the consequences

Acid and enzyme secretion

Cardia is inflamed
Decreased acid production
Gastric atrophy
Gastric ulceration

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What is the function of the antrum of the stomach?

Why is this significant?

Mucin and gastrin secretion

Antrum is inflamed
Increased acid production (because these cells produce gastrin)
Risk of duodenal ulcer

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What is the tissue structure of the stomach wall?

Mucosa:
 • Epithelium
 • Lamina propria
 • Muscularis mucosae
 • + Gastric pits

Submucosa

Muscularis propria
• Oblique
• Circular
• Longitudinal

Serosa

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Which is the most prevalent stomach cancer?

What is another, less common one?

Gastric adenocarcinoma (90%)

Gastric lymphoma (a MALToma, 5%)

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How were peptic ulcers treated originally?

How did this fall short, and why?

Blockage of gastric acid secretion
(blockage of proton pumps in parietal cells)

Ulcers would return unless acid suppression was continued. This is because the cause was not removed

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What is the cause of peptic ulcers?

Helicobacter pylori

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H. pylori was the first bacterium to be classed as a…

carcinogen

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What diseases does H. pylori cause?

peptic ulcer
chronic gastritis
gastric adenocarcinoma
gastric lymphoma

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Which countries are most affected by H. pylori infection?

Unindustrialised countries

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How does H. pylori enter the system?

Oral ingestion, usually in childhood

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How is H. pylori acid resistant?

Urase
• produces basic compounds (ammonia, urea)
• buffers the cytoplasm

Where does H. pylori hang out in the stomach?

• Adheres to the mucosa
(does not invade)
• In the mucous

Why is H. pylori so genetically diverse?

genetic drift
v. competent at transformation
high mutation rate

What are the virulence determinants of H. pylori?

vacA
babA
cagA

What is babA?

Protein allows adhesion of bacterium to gastric epithelium

What is cagA?

Gene that codes for a protein that is strongly associated with • peptic ulcers • gastric cancer through biochemical pathways in the host cell The gene is translocated into the host cell

What are some of the effects of the biochemical changes in response to cagA?

* paracellular leakage of gastric mucosa * motility * apoptosis * proliferation * cytoskeletal changes

Describe very generally the immune response to H. pylori

Considerable immune response launched | Ineffective at clearing the infection

How does H. pylori avoid immune responses?

* altered PAMPs that aren't recognised by PRRs | * Inhibit respiratory burst by macrophages

(General Question) | What are some important PAMPs in bacteria?

* flagellin | * LPS

Describe what happens when H. pylori initially adheres to epithelial cells

Cytokine release | → neutrophil infiltration

Who discovered the cause of peptic ulcers? | Why is this important?

Dr Barry Marshall and Robin Warren They challenged the accepted dogma despite criticism, and went on to win a Nobel prize for it

What is the symbol for macrophages?

Mφ

What are the later immune responses to H. pylori infection?

* Adaptive (B and T lymphocyte) induction * apoptosis of epithelial cells * disruption of mucous layer * increased gastrin released, increased acidity

Is H. pylori intra- or extracellular? | What does this mean for the immune response?

Extracellular • Humoral response is important • Th2 is important

Why don't all people with H. pylori get peptic ulcers?

• different strains • different host immune responses • genetic, environmental cofactors → NSAID use, smoking, alcohol

H. pylori was the first bacterium to be classed as a...

Carcinogen

What causes gastritis?

Disruption of normal balance between mucosal defences and damaging forces H. pylori is often responsible for this disruption

Gastritis often leads to...

Peptic ulcers

How can host polymorphisms affect predisposition to cancer?

``` Polymorphisms in genes for immunity • HLA • cytokines etc. affect the host response, and thus affect predisposition ```

What is vacA?

Pore proteins that affect endosomal compartments such as vacuoles Endosomal compartments, such as the mitochondria. Leads to release of cytochrome c from the mitochondria → apoptosis

How does smoking affect predisposition to peptic ulcer?

Impairs mucosal blood flow, and thus impairs the healing process

How is H. pylori infection treated nowadays?

* Antibiotics | * proton pump blocker to reduce acidity

What defences against infection are there in the stomach?

Acid Proteases Epithelial & mucous barrier

What is a peptic ulcer?

Breach of the mucosa | Extends from mucosa through to submucosa or deeper

What are the symptoms of a peptic ulcer?

Epigastric gnawing | Burning pain

Where do peptic ulcers occur?

Anywhere in the GIT exposed to gastric acid

Why is cure of infection a challenge?

• Antibiotic activity is altered at stomach pH

Where do H. pylori bacteria all attach?

They don't all attach, but some do attach to the gastric mucosa

What are the causal factors of Duodenal ulcers? | What are some other sequelae?

Increased acid in duodenal portion of small bowel This is a result of inflamed antrum (see below) 1. Inflamed antrum 2. Increased acid production 3. Acid in duodenum 4. Metaplasia of duodenal cells to gastric mucosal cells 5. The cells can be infected: colonisation of duodenum with H. pylori

Why does chemotaxis confer stability in the stomach to H. pylori?

It can move to the more pH neutral areas (the mucous)

H. pylori only bind to...

Gastric mucosa (in the stomach)