Balance + regulation in the gut

Question 1

What bacteria are mostly present in the gut?

Answer 1

Bacteriodetes

Question 2

What are the main roles of the microbime?

Answer 2

GI immune system development
Break down of short chain fatty acids into useful molecules
Stop colonisation of pathogenic bacteria by out competition
Degrade toxins
Vitamin synthesis

Question 3

What are the 3 main roles of SCFA?

Answer 3

• Reduce inflammation by neutrophils
• Reduce obesity and insulin resistance
• used in the liver for gluconeogenesis

Question 4

What are the main anti inflammatory + inflammatory pathogens?

Answer 4

anti inflammatory = symbionts

inflammatory = pathobionts

Question 5

What are features of healthy gut microbiota?

Answer 5

• low gut permeabiltiy
• High useful molecule e.g SCFA
• low endotoxaemia
• high anti inflammatory cytokines
• increased insulin sensitivity

Question 6

What are the main components of the mucosal immune system?

Answer 6

Peyers patches 
Mast cells
Goblet cells 
Paneth cells 
IgA secreting plasma cells

Question 7

Describe the two mucous layers

Answer 7

Outer mucous layer: Non sterile degrading mucous, mucins are released which can be used by microbiota
Inner mucous layer: Sterile mucous rich in antimicorbial peptides and IgA

Question 8

What are some of the gut defences?

Answer 8

CD8 cytotoxic T cells
Effector T cells in the lamina propria secrete anti inflammatory cytokines
Th17 cells promote defensin production
There is more Th2 and less Th1

Question 9

How are bacteria recognised by PRRS?

What happens if bacteria reach the epithelium?

Answer 9

• TLR receptors are only present on the basolateral membrane
• Can only detect bacteria that have invaded the entire epithelium
• If these bacteria reach the epithelium NFKB is activated -> TLR recruitment -> pro inflammatory cytokines

Question 10

How do dendritic cells and macrophages maintain an anti inflammatory phenotype?
What do dendritic cells + macrophages produce?

Answer 10

• Gut epithelial cells produce TSLP + TGFbeta
• dendritic cells produce retinoic acid to recruit t + b cells via CCR9 chemokine
• T + B cells produce IL-10
• Maintains anti inflammatory environment and promotes IgA class switching

Question 11

How do we sample the gut lumen for potential pathogens?

Answer 11

m cells pump antigen from the gut lumen to dendritic cells for sampling

Antigens are up taken by dendritic cells, have pseudopodes to grab antigens from the mucous

Release IL-10

IL-10 activates T regulatory cells and antibody production

Pathogen is dragged through the epithelium and phagocytosed by the dendritic cells

T cells are activated by MHC presentation

Question 12

What happens if antigens are normal?

What happens is there is PAMPS + non self antigens?

Answer 12

• IL-10 and TGFbeta are released

- Dendritic cells will induce an immune response

Question 13

How does IgA secretion occur?

Answer 13

Independent of T cells

Dendritic cells produce APRIL + BAFF cytokines along with TGFbeta to promote B cells to produce IgA

Question 14

How can salmonella evade defences?

Answer 14

• Salmonella attaches to m cells damaging them and entering the deep layers
• Dendritic cells are recruited and release co stimulatory molecules
• IL-12 -> T cells -> Th1
• IFNy enhances macrophage killing
• Th17 cells produce IL-17 + IL-23 for defensin production and neutrophil recruitment

Question 15

What type of organism is C dif and how does it cause damage?

Answer 15

Opportunistic pathogen

Neutrophils and RBC leak into the gut lumen

Question 16

How do we have oral tolerance?

Answer 16

M cells take up soluble proteins from the food
Ingested food can pass into the tissues if there is a break in the epithelium
Dendritic cells present antigen but there are no DAMPS or PAMPS ( cant activate immune system)
IL-10 released to drive Treg production + TGFbeta release

Question 17

What HLA molecule is normally present in coeliac disease and what does it allow for?

Answer 17

HLA-DQ2/DQ8
Allows for the presentation of the gluten antigen
Gluten penetrates the tissues
Dendritic cells take up antigen and present
Transglutamine converts gluten -> gliadin
B cells recognise this complex
T cells activate B cells to produce antibodies