Module 4.3

Question 1

Describe the pros and cons of the intestinal tract as a semi-permeable barrier.

Answer 1

Gastrointestinal tract (GIT):
- Open tube exposed to the external environment, part of the digestive system
- Important role in the uptake of material
Pros:
- Uptake in mucosal tissues that have small protrusions of villi that allow for increased surface area

Cons:
- Leaky Gut Syndrome: inflammation of the gut which causes redness, swelling, pain and loss of function

Question 2

Identify the role of different immune cells in the gastrointestinal environment.

Answer 2

• Salmonella is recognised and controlled by innate and adaptive immunity using different mechanisms
• Innate immunity
   Broad recognition: molecular patterns (e.g. flagellum, LPS) are commonly found on many Gram-negative bacteria; they are recognised by pattern-recognition receptors found on innate immune cells
   Direct killing of invading bacteria
   Rapid ‘danger and alarm’ response to initiate cascade of immune responses
   Activate adaptive immune cells
• Adaptive immunity:
   Specific recognition: specifically recognise antigens derived from the pathogen; this response takes a little while to develop upon first encounter but becomes more efficient upon re-encounter in life
   T-cells: recognise small peptide antigens (commonly 9-20 residues)
   Antibodies: recognise peptides and other biochemical structures

The mode of recognition highlights different functions of innate and adaptive immunity:
1. Innate immunity
- Dendritic cell: patrol the body and constanly monitor for the presence of foreign antigens
- Macrophage: kills microorganisms, removes dead cells, stimulates actions of other immune cells
- Mast cell: protect body from toxins and pathogens, are major producers of histamine
- Natural killer cell: destroy infected and diseased cells
- Granulocyte: an immune cell that has granules with enzymes that are released during infections, allergic reactions (asthma)
2. Adaptive immunity
- B cell: type of immune cell that makes antibodies
- T cell: direct fighters of foreign invaders
- Anitbodies: proteins that protect you when an unwanted substance enters the body

Question 3

Describe the role of diarrhoea during a gastrointestinal infection.

Answer 3

• Diarrhoeal syndrome:
• Involves the production of enterotoxins within the small intestine following ingestion of heat-resistant B.cereus spores
• Nhe – non-haemolytic enterotoxin
• HbI – haemolytic enterotoxin
• Both enterotoxins are heat labile
• Destroyed by cooking
• Both toxins are three-component toxins:
• Nhe – NheA, NheB and NheC
• HbI – L1, L2 B
• Both toxins are spore-forming toxins
• Induction of cell death pathways
• Cause cell lysis
• Causes fluid accumulation in the ileum
• Onset of diarrhoea

Question 4

Explain how microbes can contribute to gastrointestinal health and disease

Answer 4

• Mechanisms of infection:
• Arrival of a microbe at a site (encounter)
• Binding to a receptor or triggering uptake mechanisms (entry)
• Utilising host resources for multiplication (replicate)
• Release of new progeny (spread)
• Gastroenteritis:
• Inflammation of the gastrointestinal tract
• Symptoms include diarrhoea, vomiting, abdominal cramping
• Treatment involves rehydration therapy
   Most are self-limiting
• Can be infectious or non-infectious
   As a result of the microorganism
   Caused by the host response
• Inflammation and the gut:
• Five pillars: heat, redness, swelling, pain and loss of function

Question 5

Explain key features that can define a microbial pathogen.

Answer 5

• Pathogenic traits of microbes (what makes them bad):
• Promoting colonisation in novel places
• Niche settings of sterile locations
• Antagonising host defences
• Facilitating the spread of microbes
• Most will require a range of virulence factors

Question 6

Identify both viral and bacterial causative agents of gastroenteritis.

Answer 6

Bacterial agents:
- Salmonella enterica
- Clostridiodes difficile
- Bacillus cereus
Viral agents:
- Norovirus
- Rotavirus

Question 7

Explain how bacterial toxins can cause gastroenteritis.

Answer 7

• Gastroenteritis is mainly caused by bacteria
• Many different bacterial species are “enteropathogens” that cause gastroenteritis
• Many bacterial enteropathogens produce toxins
• Bacterial toxins are often responsible for the symptoms of gastroenteritis (strains that don’t produce toxins often don’t cause disease)
• Bacterial toxin-mediated gastroenteritis can be infectious or non-infectious
• A bacterial toxin is a toxic substance produced and released by a bacteria that causes damage to another cell
   Bacterial toxins are usually proteins but not always
   They come in different shapes and sizes
   They can damage different cells in different ways
• Example of enteropathogens causing gastroenteritis:
• Clostridiodes difficile
   Major hospital pathogen
   Causes gastrointestinal diseases known a CDI ranging from mild diarrhoea to life-threatening pseudomembranous colitis
   CDI is entirely toxin-mediated
   Monoclonal antibodies targeting the toxins alleviate symptoms of the disease
   TcdA and TcdB are the major toxins produced by C. difficile within the colonic niche
   The toxins are taken up by colonic epithelial cells
   Once inside the cell, the toxins target Rho-family GTPases causing cell death
   The toxins cause extensive tissue damage, GI bleeding, inflammation of the gut and fluid accumulation leading to the onset of diarrhoea
• Bacillus cereus
   Bacillus cereus is an important cause of food poisoning
   It is a spore-forming bacterium that is commonly found in soil, on vegetables and in many raw and processed foods
   It causes two different types of foodborne illness:
• Emetic (vomiting) - emetic toxin (intoxication)
• Diarrhoeal - similar to an enterotoxin
   Symptoms are generally mild and resolve untreated within 6-24 hours
   The type of symptom is independent of the toxins produced by bacteria

 Emetic Syndrome:
-Emetic syndrome is a non-infectious illness - it is an intoxication
* Involves the ingestion of pre-formed emetic toxin also known as cereulide
- Heat stable (toxin is resistant to heat, pH and proteolysis)
o Can survive cooking/baking
o Can survive passage through the stomach
* Exposure to cereulide leads to the destruction of mitochondria within intoxicated cells
* Nausea and vomiting is caused by the binding and activation of 5-HT3 receptors.
o Increased stimulation of the afferent vagus nerve
 Major nerve controlling stomach function

 Diarrhoeal syndrome:
* A diarrhoeal syndrome is a form of infectious gastroenteritis - caused by ingestion of bacteria
* Involves the production of enterotoxins within the small intestine following ingestion of heat-resistant B.cereus spores
o Nhe – non-haemolytic enterotoxin
o HbI – haemolytic enterotoxin
o Both enterotoxins are heat labile
 Destroyed by cooking
* Both toxins are three-component toxins:
o Nhe – NheA, NheB and NheC
o HbI – L1, L2 B
* Both toxins are spore-forming toxins
o Induction of cell death pathways
o Cause cell lysis
o Causes fluid accumulation in the ileum
o Onset of diarrhoea

Question 8

Explain the difference between localised gastroenteritis and systemic infection.

Answer 8

Systemic:
- The infection is present in the bloodstream and can affect entire body – multiple organs
* E.g. Salmonella invades sites that would otherwise be sterile (e.g. the spleen, liver, bone marrow and gall bladder)
Localised gastroenteritis:
- Affects specific organs

Question 9

Salmonella enterica - disease and host immunity

Answer 9

• Salmonella enterica is a faecal-orally transmitted bacterial pathogen and is a major food safety risk
• Pathogenic serovars of Salmonella enterica can cause several notifiable diseases in Australia
• Gut lumen:
• Luminal space provides an extracellular niche for Salmonella growth
• Faecal shedding is the natural route of transmission
• Interaction with other gut flora can affect disease pathology
• Systemic dissemination:
• Salmonella invades sites that would otherwise be sterile (e.g. the spleen, liver, bone marrow and gall bladder)
• Predominantly grows in intracellular niche (e.g. salmonella-containing vacuole) of infected cells
• Salmonella controlled by various host immune cells

Question 10

Summary of risk factors, assessment, diagnosis and prevention

Answer 10

• Bacterial gastroenteritis:
• Gastroenteritis refers to syndromes of diarrhoea or vomiting resulting from non-inflammatory infection in the upper small bowel or inflammatory infection in the colon
   It can be caused by bacteria, viruses or parasites (mainly bacteria)
• Risk factors:
   Weaning
   Age
   Gastric acidity
   Intestinal dysmotility
   Antibiotics
   Immunosuppression
   Genetic predisposition
   Overcrowded living conditions
   Poor sanitation
• Assessment and management:
   Rehydration
   Nutrition
   Empirical antibiotic therapy
   Hygiene and sanitation
• Diagnosis:
   Adjunctive therapy
   Notification
   Prevention of nosocomial transmission
• Prevention of gastroenteritis:
   Dietary awareness
   Non-antibiotic options
   Prophylactic antibiotics
   Vaccines