0219 - Mucosal Protection in the Gut

Question 1

Describe in detail the microbial protective mechanisms in the gut.

Answer 1

Normal flora compete with pathogens for nutrients and attachment to epithelial cells.
Normal flora also produces anti-microbial substances (Bacteriocins and SCFAs) that kill or inhibit pathogenic growth and colonisation.

Question 2

Describe in detail the physical protective mechanisms in the gut.

Answer 2

Physical epithelium barrier between lamina propria and lumen. Tight junctions ensure this is a good seal (pathogens need to colonise or cross these barriers).
Epithelial cell turnover of damaged cells, together with peristalsis, expel pathogens and normal flora in faeces.

Question 3

Describe in detail the chemical protective mechanisms in the gut.

Answer 3

Bile - antibacterial
Enzymes - Pepsin, pancreatic (trypsin, chymotrypsin, lipase), and lysozymes are all antibacterial.
Gastric Acid
Mucus - Provides a protective barrier and chemical barrier against acid.

Question 4

Describe GIT mucus as a chemical protective mechanism

Answer 4

Viscous, hydrophobic gel that prevents microbial adhesion and contains IgA to exclude pathogens. Composed of glycoproteins, and constantly refreshed.
Secreted by surface/neck mucus cells (stomach), and Brunner’s glands (duodenum)/Goblet cells (intestine and respiratory tract).
Contains IgA and HCO3- to protect against microbes and acid respectively.

Question 5

What are the components of the Gut-associated lymphoid system (GALT)

Answer 5

Consists of Peyer’s Patches, isolated lymhpoid follicles of intestine, mesenteric lymph nodes, appendix, and tonsils/adenoids.

Question 6

What are Peyer’s Patches?

Answer 6

Components of the GALT, essentially GIT lymph nodes. Consist of many B cell follicles, with germinal centres and smaller T-cell area. Subepithelial Dome rich in dendritic cells, T and B cells. Covered by follicle-associated epithelium, containing enterocytes and specialist ‘microfold M-cells’ to separate from lumen. Present in foetal gut.

Question 7

What are Isolated Lymphoid Follicles (ILFs)?

Answer 7

Microscopic aggregation of organised lymphoid tissue with covering epithelium of enterocytes and M-cells (like Peyer’s patches). Unlike Peyer’s patches, contain mainly B cells and develops only after birth.

Question 8

What are the two mechanisms of direct antigen uptake in the gut?

Answer 8

Uptake by Peyer’s patches, mediated by M-cells.

Direct uptake by dendritic cells.

Question 9

Describe M-cell mediated uptake by Peyer’s patches.

Answer 9

M-cells uptake antigen by endocytosis and phagocytosis. It is transported in vesicles and released at basal surface (transcytosis). Antigen is bound by dendritic cells which then activate T-cells.

Question 10

Describe direct antigen uptake by dendritic cells.

Answer 10

Dendritic cells extend processes from basal surface, between epithelial cells, and acquire antigens. They then transport to T-cells in mesenteric lymph nodes.

Question 11

Which type of T cell predominantes in lamina propria? Which in epithelium?
KEY EXAM CONCEPT

Answer 11

CD4 in lamina propria, CD8 in epithelium. If epithelium infected, you want it killed.

Question 12

What are the four triggers for an immune response in the gut?

Answer 12

Epithelial-triggered (via TLR/NOD)
IgA-mediated (via transcytosis)
CD4-based (Pathogen captured by dendritic cell, invokes strong immune response).
CD8-based (Via MHC I on infected epithelial cells).

Question 13

Describe an epithelial-triggered immune response in the gut.

Answer 13

Invading pathogens trigger either TLRs (basolateral surface/vacuoles) or NODs (cytoplasm), leading to inflammatory cytokines and triggering influx of leukocytes.

Question 14

Describe an IgA-mediated immune response in the gut.

Answer 14

Antigen activates B-cells, which switch from being IgM-producing to IgA-producing and are then redistributed throughout GALT. Once in lamina propria, they secrete IgA into subepithelial space, where it undergoes transcytosis to reach target antigens in lumen. If antigen is in lamina propria, bound IgA can be transcytosed into lumen to export the antigen.

Question 15

Describe a CD4 T-cell-based immune response in the gut.

Answer 15

Pathogens that penetrate epithelium activate dendritic cells to give a very potent immune response. Dendritic cell presents to CD4 in lamina propria, generating effector Th1 (activate macrophages) and Th2 (activate B-cells) cells.

Question 16

Describe a CD8 T-cell response.

Answer 16

MHC1 antigens are recognised by intraepithelial CD8, which kill infected cell.

Question 17

How does the body develop immunological tolerance to food?

Answer 17

Mucosal dendritic cells recognise food antigens and give weak co-stimulatory signals to CD4, ensuring anti-inflammatory (Th3) or Treg cells are generated, preventing an immune response.

Question 18

How does the body prevent an immune response to normal flora?

Answer 18

Flora cannot penetrate epithelium, and no TLRs/NODs on apical surface. Even if taken up by dendritic cells, TGF-beta, TSLP and PGE2 are produced by gut epithelial cells, maintaining dendritic cells in a quiet state, ensuring Th3 and Treg cells are produced. However, lack of this tolerance in systemic immune system means full-blown immune response if they do enter rest of body.

Question 19

Production of PGE2, TSLP, and TGF-Beta inhibits the maturation of what cell type?
KEY EXAM CONCEPT

Answer 19

Dendritic cells.

Question 20

What is the key deciding factor between generating an immune response or tolerance in the GALT? How is this factor mediated?

Answer 20

Activation status of local dendritic cells, mediated by presence or absence of inflammation.