L13. Benefits and Mischiefs of Normal Microbiota 2

Question 1

The intestinal microbiota interacts with the immune system to affect the functionality and development of it. What are the 4 major ways it does this?

Answer 1

1. Production of the mucous layer
2. Renewal and development of epithelial cells
3. Development of lymphoid structures
4. Development of specialised lymphoid subsets

Question 2

What are bacteriocins?

Answer 2

They are proteinaceous toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s) - protective.

Question 3

What is the indirect way that the microbiome affects the immune receptor distribution in the gut epithelium?

Answer 3

Pattern Recognition Receptors (PAMPs) are localised and compartmentalised in ways that only when bacteria enter compartments, does it initiate the immune response [limits unwanted activation to normal microbiome]

Question 4

Describe the distribution of some pattern recognition receptors on enterocytes

Answer 4

TLR 2 and 4 are expressed highly before birth but downregulated after and are expressed on the microvilli

TLR 3,7,9 are expressed in the endosomes (RNA and DNA antigens)

TLR 5 (flagellin) is on the baso-lateral surface

Question 5

What happens upon pamp recognition and signalling?

Answer 5

Proliferation of crypt enterocytes and paneth cells
Release of more antimicrobials
Induced cytokine production and secretion

Question 6

Describe the development of the lymphoid structures

Answer 6

Peyers patches and the mesenteric lymph nodes develop PRE-NATALLY

The LTi cells, ILFs develop POST-NATALLY as a result of microbiome signalling.

However microbes entering via the M cells leads to further development of the peyer’s patches post-natally.

Question 7

When does the development of the Lymphocyte subsets occur?

Answer 7

Upon the acquisition of intestinal microbiota occurs (after PAMP interactions)

• PAMP interactions promote IL-22 producing NK-22 cells
• Restricts differentiation of invariant NK T cells
• Cause the production of MAIT cells
• Induces cytokines like TGFb and others to influence the DCs to produce the non-inflammatory responses

Question 8

What is physiological inflammation in the gut? How is this different to pathological inflammation?

Answer 8

Physiological inflammation is when normal microbiota acts on MALT to produce an effective, chronic innate and adaptive response without damage to the host.

Pathological inflammation is in response to pathogenic organisms through PAMP recognition and causes damage to the host

Question 9

How is the microbiota hypothesised to be involved in Obesity?

Answer 9

High fat diets = decreased diversity of microbiome = higher levels of insulin resistance, serum triglycerides, cholesterol and insulin.

Can transfer obesity if you transfer the microbiome

Question 10

Obesity is a low grade inflammatory disorder. What is meant by this?

Answer 10

Obesity is associated with induction of inflammatory cytokines and increase in mast cells, T cells and macrophages.
This kind of signalling desensitises insulin receptor and leptin receptors

Question 11

How can the microbiome be detrimental to the host?

Answer 11

Escape the GIT and cause infections in extra-intestinal sites such as the UT, RT, wounds, peritoneum and blood stream

This usually requires an abnormality in the host function such as altered immunity, anatomical changes (eg. surgery)

Question 12

What is the risk of the microbiome in terms of resistence?

Answer 12

As they are able to survive in the host, they have certain evasion mechanisms to the host. They are in risk of transferring their DNA to another, pathogenic host making it very dangerous.

Conversely, pathogenic bacteria may transfer their resistance or pathogenicity to commensal flora.