Exploring Biomedicine 2024: Gastroenteritis

What are the pros of the intestinal tract as a semi-permeable barrier

• absorbance of nutrients for function

• create an immune system where peyer’s patches can sample what is in the intestinal lumen

What are the cons of the intestinal tract as a semi-permeable barrier?

What is the role of different immune cells in the GI environment?

Describe the role of diarrhoea during a GI infection

Explain how microbes can contribute to gastrointestinal health

• Protective functions

• Structural functions

• Metabolic functions

What are metabolic functions of good microbes?

control IEC differentiation and proliferation

• metabolise dietary carcinogens

• synthesise vitamins

• nutrient uptake

• ferment non-digestible dietary residue and endogenous epithelial derived mucus

• ion absorption

• salvage of energy

What are structural functions of good microbes?

• barrier fortification

• induction of IgA: induce antibody formation

• apical tightening of tight junctions

• immune system development

What are protective functions of good microbes?

• pathogen displacement: prevents pathogenic strains from reaching layers

• nutrient competition

• receptor competition

• production of anti-microbial factors e.g. bacteriocins, lactic acids

• commensal bacteria: immune system recognises these are good

explain how microbes can contribute to gastrointestinal disease

• hide inside other cells

• use host machinery to spread further

• damages host

• goal: gain enough nutrients to spread genetic info

What are examples of bacteria contributing to GI disease?

Bacillus cereus

salmonella enterica

escherichia coli - dependent on how they replicate to fit the niche by chance causes damage

What are examples of viruses contributing to GI disease?

Norovirus (2 bucket disease)

Rotavirus (common in children)

What are examples of parasites contributing to GI disease?

Giardia intestinalis

entamoeba histolytica

What are the 3 ways pathogens can leave the gut to the body?

1. express virulant factors to infect epithelial cells

2. come to gut lumen and fight for space/nutrients where eventually M cells are infected

3. passively captured by dendritic cells where they are collected by lymph nodes and cause sepsis when they enter the blood

What is the ‘natural route of transmission?

faecal shedding

What are the metabolic functions of good microbes?

• control IEC differentiation and proliferation

• metabolise dietary carcinogens

• synthesise vitamins

• nutrient uptake

• ferment non-digestible dietary residue

• ion absorption

• salvage of energy

What are structural functions of good microbes?

• barrier fortification

• induction of IgA: antibody formation

• apical tightening of tight junctions

• immune system development

What are the protective functions of good microbes

• pathogen displacement: prevents pathogenic strains from reaching layers

• nutrient competition

• receptor competition

• production of anti-microbial factors (lactic acids)

• commensal bacteria recognised by immune system

Where is microbe diversity highest?

in the colon

then jejunum then ileum

What is microbe distribution and diversity affected by?

tissue and host condition

disease can change biodiversity

• less in one type and more in another

• shift depends on health

Explain key features that define a microbial pathogen

Promoting colonisation in novel places

• niche settings of sterile locations (e.g. blood/urine)

• Antagonising host defenses (stop host defenses from functioning to preserve own life)

• Facilitating spread of microbes

• require a range of virulence factors (control cell, affect proteins, inject genomic info)

What are the steps in the mechanism of infection?

1. arrival of microbe at the site (encounter)

2. binding to a receptor or triggering uptake mechanisms: set up niche to start performing actions (entry)

3. utilising host resources for multiplication (replicate)

4. release of new progeny (spread)

identify both viral and bacterial causative agents of gastroenteritis

bacillus cereus, salmonella enterica, Escherichia coli

norovirus, rotavirus

Where are immune cells found in the GI tract?

lamina propria which need to differentiate between good and less good microbes

What is non-infectious gastroenteritis?

host response to just the toxin being ingested

• emetic (vomiting)

• ingestion of preformed emetic toxic

• can be resistant to heat, pH, and proteolysis

• destorys mitochondria of intoxicated cells

• vomiting caused by binding and activation of receptor causing increased stimulation of afferent vagus nere which controls stomach function

What is infectious gastroenteritis?

The presence of the microorganism and the toxin causing the disease

diarrhoea

production of enterotoxins

Nhe and Hbl punch hole through cell membrane

Pore forming bacteria: induction of cell death and fluid accumulation in the ileum

What is treatment for gastroenteritis?

rehydration therapy: self-limiting as most people don’t have access to resources for treatment

What are symptoms of gastroenteritis?

• diarrhoea

• vomiting (loss of fluid)

• abdominal cramping

What are the mechanisms of inflammation?

heat: more blood flow to area and heat can help remove pathogens or cause more damage

redness: more blood flow to the area

Swelling: causes leaky gut

• movement across the faulty tight junctions

• fluid from blood leaks into interstitial spaces causing swelling

• dilation of blood vessels - causes loss of tight junctions between cells = redness

Pain: impinging nerves

Loss of function: so much damage in the area

What is gastroenteritis?

Inflammation of the GIT

explain how bacterial toxins can cause gastroenteritis

• commonly a protein

• different shapes and sizes

• damage range of cells - colonic epithelial cells or haemocytes in liver

• damage cell in different ways - punch a hole or taken up and inhibit cellular pathway

Only strains of bacteria that produce a toxin cause disease

What is localised gastroenteritis?

localised gastroenteritis is when the pathogens remain in intestine and do not infect anywhere further

What is systemic gastroenteritis?

When the pathogen invades sites which would otherwise be sterile (spleen, liver, bone marrow, gall bladder). Can be protected for years before being released back throughout body

mostly grows in intracellular niches of infection cells allows for greater survival rates but limited space

What is innate immunity?

• rapid response

• short lived

• initial defense

• need to have to survive infection

• broad

• context

• dendritic cells, macrophage, mast cells, natural killer cell, granulocyte

• recognised by pattern recognition receptors and involve a direct killing of invading bacteria for rapid ‘danger and alarm’ response to initiate cascade of immune responses which activates adaptive immune system

What is the benefit of the innate immunity and adaptive immunity working together?

for infection control to maintain a healthy balance

What is adaptive immunity?

• takes hours/days to occur

• highly specialised and coordinated response

• specifically targets toxins

• secondary response - has memory of past infections

• specificity

• B-cell, T-cell, CD4*T-cell, CD8*T-cell, antibodies

• specifically recognise ANITIGENS derived from pathogen

• T-cells: recognise small peptide antigens

• Antibodies: recognise peptides and other biochemical strutures