2-30 Gut Immunity

Question 1

What features characterize mucosal immunity?

Answer 1

• Proactive approach
• Mucus barrier
• Large population of resident immune cells
• Macrophages resident in mucosal tissues do not initiate inflammation in response to penetration of the epithelial layer
• Less T cell activation

Question 2

Which anatomical structures contribute to mucosal immune surveillance?

Answer 2

Waldeyer’s Ring: adenoids, palatine, and lingual tonsils form a ring of lymphatic tissue around the alimentary canal

Appendix: rich in lymphoid follicles, located at junction of large and small intestine

Question 3

Which microscopic structures contribute to immune surveillance?

Answer 3

Throughout the intestinal walls are microscopic immune aggregates (Peyer’s patches of T and B lymphocytes and dendritic cells) that carry out more localized surveillance and response activities.

Potential antigens pass through M (microfold) cells via transcytosis and are transported to Peyer’s patches to be evaluated by dendritic cells.

Question 4

What cells direct the gut immune response, and what do they do?

Answer 4

CD103+ dendritic cells take up antigens from digested food, commensal microorganisms, and potential pathogens, and present them to antigen-specific T cells. CD103+ DCs direct the immune response in one of two possible directions:

1. Soluble proteins/food macromolecules → oral tolerance
2. Microbial Ags → antibody response: CD4+ T cells activated → pair w/ antigen-specific B cells → provide T-cell assistance for Ab production

Question 5

What is oral tolerance?

Answer 5

Achieved when CD103+ DCs encounter soluble proteins or other macromolecules derived from foods.

Ag-specific T cells reactive to fragments of these harmless molecules are rendered anergic (through lack of co-stimulation) or can be induced to become Tregs through DC secretion of IL-10. No adaptive response occurs, and no Ab is generated against the Ag.

Question 6

How are lymphocytes directed to GI mucosal tissues to fight infection?

Answer 6

Lymphocyte cell surface receptors (low [CCR7] → high [integrin α4:β7] and [MAdCAM-1]) direct naïve and activated cells to proper locations.

Question 7

What are some immune cells found in a healthy intestine?

Answer 7

Because of immune cell homing to mucosal tissues, there is a large population of resident immune cells in healthy gut tissues.

Question 8

How does the gut protect its mucosal surfaces?

Answer 8

Secreted immunoglobulins.

Activated B cells that have effectively homed to the mucosal lamina begin to secrete antigen-specific IgM. Most undergo affinity maturation and switch isotypes to produce IgA antibodies (IgA1 and IgA2), which are actively transported across the epithelium and into the lumenal mucus.

Question 9

What are the two kinds of IgA?

Answer 9

IgA1 looks like an ‘L’–for “long” hinge. Better flexibility and binding, but susceptible to proteolytic cleavage. Predominates among lower bacterial numbers.

IgA2 looks like an inverted ‘S’–for “short” hinge. Less susceptible to cleavage, but worse binding. Found among higher bacterial concentrations.

In its secreted form, IgA is dimeric and joined by a J chain.

Question 10

What best resolves parasitic worm infections?

Answer 10

TH2 subset of CD4+ helper T cells