Immunology Of The Gut

Question 1

What is the role of the mucosal surfaces in the gut?

Answer 1

Portal of entry for non-pathogenic organisms such as food and commensal flora.

Question 2

How does the composition of flora change in the gut?

Answer 2

Greatest concentration found in the colon.

Question 3

What is the histology of the gut?

Answer 3

Tightly linked Epithelial layer of enterocytes lined with microvilli, which increase the SA for absorption and crypts containing stem cells for regeneration. The epithelia contains tight junctions composed of Claudins and occludins. Goblet cells are present here to create a mucosal layer containing IgA for immune defence.

Below this is the laminate propia, a dense connective tissue which is concentrated in immune cells and Peyer’s patches, for clearing of antigens from gut into lymphatic systems

Question 4

What do the stem cells in the crypt give rise to?

Answer 4

Components of the intestinal epithelia such as:
Goblet cells for mucus production
Enterocytes for absorption
Paneth cells for anti-microbial peptide production.

Question 5

What are Paneth cells?

Answer 5

Generated by crypt stem cells that are responsible for production of anti-microbial peptides such as alpha-defensins.

Question 6

What is the intestinal lumen?

Answer 6

Contains food particles, bile and digestive enzymes. It is in contact with the apical mucosal layer of the intestine.

Question 7

What are the layers of the intestine?

Answer 7

Intestinal lumen
Mucosal layer
Epithelial layer
Lamina Propia
Peyer’s patches

Question 8

What is the innate immune system?

Answer 8

Low specificity using pattern recognition receptors Includes dendritic cells, macrophages, monocytes and granulocytes.

Question 9

How is recognition achieved in the adaptive immune system?

Answer 9

T cell receptor and B cell receptor.

Question 10

What are the progenitors of CD4+ T cells

Answer 10

MHC Class II restricted cells which have helper functions which include:
Th1 cells
Th2 cells
Th3 cells
T regulatory cells
CD25+ T cells

Question 11

Which CD4+ T cells inhibit an immune response?

Answer 11

T regulatory cells that produce IL-10
CD25+ T cells that produce IL-10 and TGF-beta
Th3 cells that produce TGF-Beta.

Question 12

Which CD4+ T cells promote immune response?

Answer 12

Th1 cells that produce IFN-gamma
Th2 cells that produce IL-4 and IL-5.
Th17 cells that produce IL-17.

Question 13

What are the pro-inflammatory cytokines?

Answer 13

IL-4, IL-5, IL-17 and IFN-gamma produced by:
Th1, Th2 and Th17 cells.

Question 14

What are the anti-inflammatory cytokines?

Answer 14

IL-10 and TGF-beta produced by
T reg cells, Th3 cells and CD25+ T cells.

Question 15

What is the role of Th1 cells?

Answer 15

Immunity against intracellular pathogens and produces IFN-gamma. Involved in auto-immunity and chronic inflammation.

Question 16

What is the role of Th2 cells?

Answer 16

Immunity against extracellular pathogens and produces IL-4, IL-5. Involved in atopy such as asthma.

Question 17

What is the role of Th17?

Answer 17

Immunity against extracellular pathogens like bacteria and fungi, by producing IL-17. Involved in autoimmunity and chronic inflammation.

Question 18

What are the lymphoid tissues of the gut?

Answer 18

Peyer’s patches
Isolated lymphoid follicles
Mesenteric lymph nodes
Lamina propia leukocytes
Intraepithelial leukocytes

-> These GALTs produce the most immunoglobulins in the body.

Question 19

Where are the isolated lymphoid follicles located?

Answer 19

They are single B cell follicle with a germinal centre located throughout the intestine.

Question 20

Where are Peyer’s patches located?

Answer 20

Found only in the small intestine in the ileum.

Question 21

Where are the mesenteric lymph nodes located?

Answer 21

Largest lymph nodes in the body which drain the lymphoid tissue of the entire intestinal tract:
Peyer’s patches
Intrapeithelial leukocytes
Lamina propia leukocytes

Question 22

What are the effector lymphatic tissues in the gut?

Answer 22

They are scattered lymphoid tissue and include lamina propia leukocytes and intraepithelial leukocytes.

Question 23

What are the intraepithelial leukocytes?

Answer 23

Lymphoid tissue in the epithelial layer for immune defence, containing different types of T cells.

Question 24

What are the immune cells of the lamina propia?

Answer 24

CD4+, CD8+, Macrophages, dendritic cells and plasma cells.

Question 25

How are antigens transported to Peyer’s patches

Answer 25

The antigen is transported across the epithelial lumen to the peyer’s patches by M cells via transcytosis. This is captured in a vesicle and delivered by MACROPHAGES to T cell areas and present on MHC receptors for activation of T reg lymphocytes in Peyer’s patches. B cells will produce IgA antibodies to be delivered to the lamina propia for mucosal protection of the gut.

Question 26

What is transcytosis?

Answer 26

Endocytosis and phagocytosis.

Question 27

What is the target by pathogens to gain entry into the subepithelial space?

Answer 27

M cells due to antigen capture. Salmonella, poliovirus and shingles

Question 28

What suppresses immune response in a healthy intestine

Answer 28

Macrophages producing IL-10 and dendritic cells producing TGF-beta.

Question 29

How are macrophages involved in the gut?

Answer 29

They have projections between the epithelial cells to allow antigen to bypass the M cells and directly transfer to dendritic cells.

Question 30

How do metabolic end-products affect the immune system?

Answer 30

End products of bacterial metabolism stimulate T regulatory cells and naive T cells.

Question 31

What form is IgA in the blood?

Answer 31

Monomeric form.

Question 32

What form is IgA in the blood?

Answer 32

Dimeric form where two IgA molecules are linked by a J chain.

Question 33

How does IgA binding work?

Answer 33

Dimeric IgA travels through the crypts of epithelia to enter the intestinal lumen and take up antigens for neutralisation.

Question 34

How is IgA transported across the lumen?

Answer 34

IgA binds to the poly-Ig receptor which has a high affinity for Dimeric IgA on the basolateral aspect of the epithelia which takes it in by endocytosis to form a vesicle. Transcytosis causes the released IgA to be cleaved by proteases and result in a complex called secretory IgA.

Question 35

What is secretory IgA?

Answer 35

Two IgA molecules linked by a J(joining) chain, bound to poly-IgR receptors. This is formed by protease activity. It cannot induce inflammation because it cannot activate classical complement system or opsonisation so it is anti-inflammatory. Secretory IgA limits access of pathogens to the mucosal surfaces by neutralising toxins and pathogens.

Question 36

What is the role of the poly-IgR receptor?

Answer 36

Present in secretory epithelium for the transport of IgA and IgM.

Question 37

What replaces IgA mucosal secretions in deficient patients?

Answer 37

IgM.

Question 38

What is the role of the mucosal layer?

Answer 38

Mount immune response against pathogens and ignore harmless antigens in food.

Question 39

Why is there no immune response against food?

Answer 39

Due to oral tolerance, as a result of stimulation of T regulatory cells and inactivation of T effector cells.

Question 40

How do commensal affect the immune system?

Answer 40

They are found in the mucosal layer with no contact with TLR receptors on the intestinal epithelia. This lack of contact means in normal physiological conditions, IgA cells and T regulatory cells are induced because of their anti-inflammatory effects. Conditioned dendritic cells favour dampening of the immune response.

Question 41

How are dendritic cells activated?

Answer 41

In presence of pathogens, they become reconditioned and induce activation of CD4+ T effector cells

Question 42

Where are the TLR receptors on the intestinal epithelia?

Answer 42

Base of intestinal crypts
Intestinal epithelia surface

Question 43

How does salmonella stimulate an immune response?

Answer 43

Virulence factors through Type 3 secretion system.