1. Gut microbiota and immunity
“毕业论文答辩模版”字体为“MstiffHei HKS”需繁体输入才能正确显示简体中文
答辩人：本硕二班二组

2. CONTENTS Modulate immune cell differentiation immunity→microorganism
Tweak the production of immune mediators
Induce the development of lymphoid structure
Background

3. Role
Function
Challenge
Background

4. Role Function Background
In adult intestine, a total of about 1014 bacterial cells are present, which is ten times the number of human cells in the body. In fact, the metabolic capacity of gut microbiota equals that of the liver, and the gut microbiota can therefore be considered as an additional organ.
Function
1.Facilitate the metabolism of otherwise indigestible polysaccharides and produce essential vitamins.
2.They are required for the development and differentiation of host’s intestinal epithelium and immune system .
3.They confer protection against invasion by opportunistic pathogens ect

5. Background
Challenge
The dynamic fluctuations in the microbiota and their close proximity to epithelial tissue represent a massive challenge to immune system as microbial growth has to be restricted to a beneficial homeostasis. Furthermore, activation of the host immune system has to be controlled to circumvent the detrimental effects of chronic inflammation.

6. Immunity~microbiota Self or non-self Mucosal immune system→
Requirements
Immunity~microbiota

7. Self Requirements Immunity~microbiota
1.The realization that we live in a microbially dominated world and in fact benefit greatly from our microbiota has led to a paradigm shift in immunology.
2.Thus the definition of self in the superorganism theory has been extended to incorporate the constituents of both our own body and our microbiota.
3.Tolerance rather than responsiveness
Requirements
1.Mucosal immune system has to be tolerant towards the huge number of mutualistic microorganisms.
2. It has to assure a beneficial microbiota composition by keeping pathobionts in check, restricting microbial overgrowth and reacting to penetrating microorganisms.

8. microbiota~lymphoid structure
Gut-associated lymphoid tissue →
microbiota~lymphoid
structure

9. GALT Inclusion Peyer's patches，（PP） Mesenteric lymph nodes
Isolated lymphoid follicles，(ILFs)
GALT
Vermiform appendix，（VA）......

10. Process Forma tion Maturation
GALT is initiated pre-natally in the sterile environment of the fetus through induction by lymphoid tissue inducer (LTi) cells.
Maturation
Maturation of these tissues, including an increase in tissue size and the development of germinal centres, depends on postnatal microbial colonization

11. Stromal organizer cells
Process
Mesenchymal cells
Induced by retinoic acid to produce CXC chemokine ligand 13(CXCL13) 1
LTi precursor cells 5 2
GALT formation
CXCL13 recruit and cluster the LTi precursor cells and their maturation into LTi cells
Stromal organizer cells
LTi cells 4 3
Express several cytokines and adhesion molecules that attract further immune cells
Induce the differentiation of stromal organizer cells

12. Example PRR-NOD1 Gram-negative TLRs bacteria Stromal, CCR6 on
surface peptidoglycan
Stromal,
Epithelial
cells
CCR6 on
LTi cells
Express CC-chemokine ligand 20 and β-defensin 3
Activate ILF
formation

13. microbiota~immune mediators
IgA
AMPs
microbiota~immune
mediators

14. SIg A dendritic flagellin cells IgA-producing B cells plasma cells IgA
TLR5
B cells
IgA-producing
plasma cells
IgA
PD1-deficient mice harbour an altered IgA
altered IgA repertoire then shifts the normal gut microbiota composition

15. production classification AMPs
1.They are produced by IECs as a consequence of their tight contact with a dense and highly diverse microbial community.
2.It not only help to sustain host–microorganism segregation, but also affect the microbiota composition.
classification
1.defensins C-type lectins (such as REG3β and REG3γ)
2.ribonucleases (for example, angiopoietin 4 (ANG4))
3.S100 proteins (for example, psoriasin (also known as S100A7))

16. microbiota~immune cell differentiation
RORγt+Nkp46-LTi-like cell
iNKT cells →
specific T cell
microbiota~immune cell differentiation

17. 1.Promote intestinal barrier function by modulating mucosal homeostasis
RORγt+Nkp46-LTi-like cell ↓
RORγt+Nkp46+NK-like cell
IL-22
IL-23 and intestinal microbiota

18. 1. 2. IL-22 Promote the integrity of the intestinal barrier
Reduce bacterial infiltration by inducing epithelial repair
（1）STAT3
（2）Produce antimicrobial proteins

19. 2.Promote homeostasis by decrease iNKT cells
iNKT cell：a unique T cell subset that expressan invariant T cell receptor α-chain
Function：promote inflammation.Secret pro- inflammatory Th1and Th2 type chemokines and cytokines.Such as IFN-r，IL and TNF.

20. T cells are important “legislators” of intestinal homeostasis .
pro-inflammatory immune response:Th1、Th2、Th17.
T cells
anti-inflammatory immune response:CD4+CD25+FOXP3+ Treg cell.
The balance between pro- and anti-inflammatory T cells determines the overall equilibrium.

21. 3.Several gut microbiota drive specific T cell response.
(1)Bacteroides fragilis（脆弱拟杆菌）
(2)Clostridia（梭状芽孢杆菌）
(3)Segmented filamentous bacteria/SFB
（分节丝状菌）

22. Gram-negative bacterium
Bacteroides fragilis
Gram-negative bacterium
Elicit an anti-inflammatory response by inducing the differentiation of CD4+ T cell into Treg cell.
Treg cells produce IL-10 and supress the pro-inflammatory Th17 response, which mediated by polysaccharide A（PSA）.
CD4+T cell → signalling cascade involving MYD88→Treg cell
TLR2

23. Clostridia
Gram-positive class
Induce the expansion of Treg cells in the mucosal lamina propria
Increase levels of the immunosuppressive cytokine IL-10.
IL-10: inhibit the release of inflammatory mediators of mononuclear macrophage, furthermore, enhance the release of anti-inflammatory cytokines.

24. SFB
Elicit a pro-inflammatory immune response by promoting the differention of Th17 cell and, to a lesser extent,Th1 cell
SFB reside are in contact with epithelial cells to invade those cells
Local actin poymerization in the epithelium
Initiate a signalling events that activate the differentiation of Th17 cell .
Scanning electron microscopy of intestine in mice colonized with SFB

26. THANKS!