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Basic understanding of Immune Bowel Diseases

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## The gut microbiota and intestinal immunity
### Structure of the gut
1. Gut lumen: food antigen, commensal bacteria
2. Mucus layer:
3. Epithelial cell layer
1. Secrected bacterial products: captured by
1. macrophages,
2. neutrophils,
3. dendritic cells
2. Lamina propria
>The intestinal immune system is specialised to deal with the huge antigenicloadinthegut

Commensal bacteria in the intestine

  • Inflammatory bowel disease
  • Colon cancer
  • Type I diabetes
  • Obesity

The balance between immunity and tolerance in the gut

  • Barrier function of the intestine
  • Tight regulation of the immune system in the intestine

Barrier function: epithelial cells

  • More than just a physical barrier
    • Produce anti-microbial peptides
    • Produce cytokines and chemokines to modulate the immune system
  • Mucus: an important barrier
    • Composed of mucins
      • Massive glycoproteins made by goblet cells

Control of the intestinal immune system

  • Rich in immune cells
  • Rich in lamina propria
  • Some in the epithelial cell compartment
  • [[LgA]] from B cells controls the growth and invasion of microbiota
  • Innate lymphoid cells: important effector

T cells

  • A lot of regulatory T cells in the intestine
    • Crucial suppressive CD4+ T cell subset
  • Inhibit self-harmful T-cell reactions
  • origins
    • The thymus during T cell development（natural Tregs）
    • The periphery from CD4+ T cells (induced Tregs)
  • high proportion of T-regs are induced by specific commensal bacteria (Clostridium family)
  • Tregs less than effector T: Inflammation
  • T cells express “homing molecules” enabling migration to tissues
  • CCR9和α4β7是免疫细胞表面表达的两种趋化因子受体，参与免疫细胞向肠道相关淋巴组织和肠粘膜的迁移。CCR9 主要在 T 细胞上表达，并与小肠上皮细胞产生的趋化因子 CCL25 相互作用。
  • α4β7 整合素在 T 细胞和 B 细胞上表达，并与粘膜寻址素细胞粘附分子-1 (MAdCAM-1) 相互作用。后者在肠道相关淋巴组织和肠粘膜的高内皮微静脉上表达。
  • CCR9 和 α4β7 与其各自配体之间的相互作用在免疫细胞归巢到肠道（包括固有层）中起着至关重要的作用，它们可以在肠道中参与免疫监视和组织稳态。

Dendritic cells

  • Intestinal dendritic
  • Antigen presentation molecule and antigen
  • Mesenteric lymph nodes/peyer’s patches
  • Clonal expansion

Dendritic cells and imprinting

  • Dendritic cells and generation of Tregs
    • Steady-state dendritic cells in the intestine generate T-regs
    • specialised dendritic cells in the intestine to promote immune tolerance
    • high number of regulatory T-cells in the intestine

Macrophages

  • Bacterial sensingviaPRRs
  • Hypo-responsive to bacterial stimulation
  • Regulatory functionsinthegut
  • Production and sensing of IL-10
  • Reducing local inflammation
  • Epithelial cell renewal
  • Non-migratory
  • Modulate T-cell differentiation in situ
  • Maintain T-regs in the intestinal lamina propria
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