Balance and Regulation in the Gut Flashcards
What can be found in the mucosal immune system?
- intraepithelial dendritic cell
- CD4 and CD 8 T cells
- IgA secreting plasma cell
- Paneth cells (secrete defensins)
- macrophages
- goblet cell
- mast cells
- Peyers patches:
(which are clusters of B and T cells, follicular DCs and macrophages to form germinal centres):
→ B cells
→ T cells
→ follicular DCs
→ macrophages
→ germinal centre (5x more B cells than T)
Features of microbiota
- generally non-pathogenic
- constantly proliferating and being passed out of gut
Features of Outer and Inner Mucus layers mucus layers in the gut
Outer mucus layer:
- non-sterile
- degrading mucus
- microbes utilise mucin carbs
Inner mucus layer:
- sterile
- rich in antimicrobial peptides
- Paneth cells produce α-defensins in small bowel and β-defensins in colon
What is IgA in the gut secreted for?
commensal bacteria in health gut
What do Paneth cells in the gut produce?
Defensins
- alpha-defensins in small bowel
- beta-defensins in colon
What do microbiota do in the gut? (4)
- produce vitamins such as vitamin K (needed for clotting factor)
- breakdown non-digestable carbs into short chain fatty acids
(acetate,propionate, butyrate) - degrade toxins into harmless components
- outcompete pathogenic bacteria
What does high levels of SCFAs mean?
lower risk diet obesity and insulin resistance and are absorbed and reach the liver and peripheral organs used for gluconeogenesis and lipogenesis
How does the GI tract maintain an anti-inflammatory environment?
TH17 cytokines
→ secrete IL-22 and IL-17
→ induce defensin expression by endothelial cells
→ Clostridiatermed segmented filamentous bacteria (SFB) are essential to the development of Th17 cells in the mouse gut
How does the GI tract maintain an anti-inflammatory environment?
T regs
→ present in large numbers
→ control the population of effector T cells
→ TH2 cells are relatively abundant in the intestinal epithelium but TH1 are kept at low numbers (an increase is seen in IBD)
How does the GI tract maintain an anti-inflammatory environment?
Intraepithelial Leukocytes
→ predominantly CD8+ these survey and remove infected/damaged cells
→ virally infected cells are detected through MHCI antigen presentation
→ Stressed cells (e.g. toxin exposure) up-regulate MIC-A and MIC-B and release IL-15 which targets them for killing
How does the GI tract maintain an anti-inflammatory environment?
TLR down-regulation
→ TLRs are down-regulated on the apical surface of the epithelium and present in the cytosol and basal surface
→ NOD can trigger inflammatory cytokine release and autophagy to remove bacteria
How do Dendritic cells sample the gut? (4)
- DC’s in Peyers patches produce IL-10 in response to antigen uptake to promote T-reg activation and IgA production
- Antibodies on FC receptors transcytose antigens to DC in lamina propria
- Apoptotic cells with bacteria phagocytosed by DCs
- DCs send processes between epithelial cells to sample gut
What happens if pathogen breaks through barrier?
Dendritic Cells rapidly recruited and release:
- IL-12
- which activates Th1
- which releases IFNγ to enhance macrophage killing
- IL-21 and 6
- which activates Th17 to release IL-17 and 22
- which induce defensins release and recruits neutrophils
When sampled, the Microbiota cause an anti-inflammatory defensive response…
COMMENSAL RESPONSE
1) epithelial cells secrete TGF-B and TSLP (thymic stromal lymphopoietin)
2) DCs + TLRs and macrophages produce IL-10
3) Foxp3 T regs in mesenteric lymph nodes - inhibit TH1 and TH17
4) IgA produced by B cells
If bacteria enter through other means an inflammatory reaction occurs…
PATHOGENIC RESPONSE
1) pathogens damage and break through the barrier
2) M cells are exploited and penetrate through destroying them and breaking barrier
3) DC cells recruited
4) IL-12 → TH1 → IFNy → enhance macrophage killing
5) IL-6 and IL-21 → TH17 → IL 17 → neutrophil recruitment
IL- 22 → induce defnesin expression
