Lecture 14: Specialized Immunity at the GI epithelial barriers

Question 1

Patients with severly reduced C3 levels tend to have

Answer 1

increased number of severe bacterial infections

Question 2

The membrane IgM and IgD on the surface of

Answer 2

are identical except for their CH chains

Question 3

The ____ contains blood and lymphatic vessels, and mucosa-associated lymphoid tissues

Answer 3

Lamina propria

Question 4

Specialized ______ cells deliver Ags across the epithelial barrier of the gut directly to subepithelial DCs that then present Ag locally in adjacent mucosal T-cell areas

Answer 4

Microfold (M) cells

Question 5

which has a larger tolerance to bacteria the small or large intestine

Answer 5

Large intestine (makes sense becaue it has more commensals)

Question 6

Epithelial cells produce anti-microbial peptides _____

Answer 6

defensins

Question 7

Most immune responses are induced by PRRs but, instead, these responses can be ______ in the gut

Answer 7

Anti-inflammatory actions

Question 8

Physical/chemical barrier of the gut is formed by _____, which prevent microbes from contacting epithelial cells

Answer 8

Mucins

Question 9

Mucins inclued secred and cell surface _____

Answer 9

glycoproteins

Question 10

The secreted mucins form what two layers of gel

Answer 10

• outer less-dense layer that is normally colonized by bacteria
• a denser inner layer that is bacteria-free
• (note both layers contain anti-microbial substances are produced by the epithelial cells aka produced Defensins)

Question 11

The apical surface of GI epithelial cells is coated with membrane-bound mucin proteins called the ____

Answer 11

glycocalyx

Question 12

Mucins are replaced by newly synthesized molecules every ____ to ____ hours

Answer 12

6-12 hours

Question 13

What cytokines can increase mucin production

Answer 13

• IL-1
• IL-4
• IL-6
• IL-9
• TNF
• IFNalpha
• elastase (from neutrophils)
• microbial adhesive proteins
• (note that these can not only icrease production but can alter mucins glycosylation which are thought to increase barrier function against pathogens)

Question 14

____ and ____ cells constitutively produce defensins to provide innate protection against luminal bacteria

Answer 14

Epithelial and Paneth cells

Question 15

Are encapsulated bacteria more resistant to defensins

Answer 15

yes

Question 16

In the small bowel, the major defensins are the _____ produced by paneth cells

Answer 16

Alpha-defensins

Question 17

The ____ defensins are produced by epithelial cells in the colon

Answer 17

Beta-defensins

Question 18

Defects in defensin production by epithelial cells is linked to ____ disease

Answer 18

Crohn’s disease, a chronic inflammatory disease that can involve the entire GI tract

Question 19

Commensal bacteria may express lipopolysaccharide, peptidoglycans, CpG DNA, and flagellin. Thus there are stringent control mechanisms to limit TLR-induced proinflammatory responses to commensal bacteria. Such as

Answer 19

• TLR signaling increases barrier function but NOT inflammation
• TLR5, which recognizes bacterial Flagellins, is exclusively expressed on the basolateral surface and thus it will be accessible only to bacteria that have invaded through the barrier
• The NOD-like receptors for flagellins are expressed in the cytosol of intesstinal epithelial cells
  
  • NOD-like receptors will activate inflammatory responses ony when pathogenic bacteria or their products gain access to the cytosol

Question 20

The dominant protective cell-mediated immune response of the gut consists of _____ cells

Answer 20

Th17

Question 21

A major mechanism for controlling responses in the gut is the activation of

Answer 21

Treg cells

Question 22

The ___ cells are specialized intestinal epithelial cells found in the small bowel epithelium overlying the Peyer’s patches and lymphoid follicles in the lamina propria

Answer 22

M cells

Question 23

In the Peyer’s patches and mesenteric LNs, DCs convert dietary Vitamin A into ____ (induced by thymic stromal lymphopoietin, TSLP)

Answer 23

Retinoic acid

Question 24

When Naive B or T cells are activated by Ag in the Peyer’s patches and mesenteric LNs, they are exposed to Retinoic Acid that induces the expression of ____ and ___. Which leads to

Answer 24

• chemokine receptor CCR9 and the integrin Alpha4beta7 on the effecotr B and T cells
• The effector lyphocytes enter the circulation and home back into the gut lamina properia because the chemokine CCL25 (the ligand for CCR9) and the adhesion molecule MadCam (the ligand for Alpha4beta7) are dispayed on lamina propria endothelial cells

Question 25