Mucosal Immunity

Question 1

How are Peyer’s Patches unique/different from peripheral lymphoid tissues?

Answer 1

• T helper population heavily biased toward Th2 response, leading to isotype switching from IgM+/IgD+ to IgA+
• Germinal centers ALWAYS present due to persistent antigen stimulation
• Th1 cells and CTLs may be induced when pathogens invade and change envt.
• Activated T and B cells express mucosal homing receptors (α4β7 and CCR9)

Question 2

What is responsible for inducing Ig switch from IgM/IgD to IgA in Peyer’s patches?

Answer 2

DCs that produce TGF-beta, IL5, and retinoic acid

Question 3

What are the gut homing receptors expressed by activated lymphocytes?

Answer 3

α4β7 and CCR9

Question 4

Where do activated B and T cells go after being activated in mucosal site?

Answer 4

leave mucosal site–> mesenteric lymph node–> lymph and thoracic duct–> circulation–> effector sites

Question 5

What does α4β7 on activated lymphocytes interact with on endothelia?

Answer 5

MAdCAM-1

Question 6

What is the ligand for CCR9?

Answer 6

CCL25 chemokine (CCL25 is attracted after MadCAM-1 and α4β7 interact)

Question 7

Homing of lymphocytes to mucosal sites involves specific interactions of both _________ and ______.

Answer 7

adhesion molecules; chemokines

Question 8

Do cells activated in peripheral lymph nodes express α4β7 or CCR9?

Answer 8

no, so they CANNOT get into the mucosa (so, if you immunize someone intramuscularly, this will not induce lymphocytes that can go to the mucosa)

Question 9

S-IgA in breast milk provides _________.

Answer 9

passive immunity

Question 10

What is the function of IgA Abs?

Answer 10

They prevent bacteria and toxins from getting access to the epithelium of mucosal tissues. (prevent infection)

Question 11

Intraepithelial lymphocytes (IELs) are _____ T-cells.

Answer 11

CD8+

Question 12

What is the function of IELs?

Answer 12

Activated IELs kill infected epithelial cells by perforin/granzyme and Fas-dependent pathways (infected cell displays viral peptide to CD8+ IEL via classical OR nonclassical MHC to activate IELs)

Question 13

AMPs are secreted by ______ cells and function to ________.

Answer 13

Paneth; stabilize the epithelial barrier and prevent bacteria from invading mucosal surfaces

Question 14

What do SCFAs do in the microbiota, and where do they come from?

Answer 14

SCFAs are produced by certain colonic bacteria; they enhance production of Tregs

Question 15

What induces oral tolerance?

Answer 15

virtually all proteins except for cholera toxin and heat labile enterotoxin from E. coli

Question 16

What is oral tolerance?

Answer 16

specific suppression of cellular and/or humoral immune responses to antigen by prior administration of the antigen by the oral route; presumably evolved to prevent hypersensitivity rxns to food prot. and bacterial antigens present in mucosal flora

Question 17

What are examples of things that do NOT induce tolerance efficiently and therefore would not be considered good tolerogens?

Answer 17

• thermally and chemically denatured proteins (antigen structures lost)
• viruses and bacteria (pathogens)

Question 18

In terms of tolerogen dose effects, what is more important than total doses delivered?

Answer 18

continuous exposure to antigens (low dose exposure each day will give you profound tolerance)

Question 19

What is the first line (innate) defense of mucosal immunity?

Answer 19

epithelial cells

Question 20

Do lamina propria macrophages respond to LPS on gram-negative bacteria?

Answer 20

No, which is part of the reason why our immune system does not attack commensal gram-negative bacteria. If TLRs on macrophages are not responding to LPS, then the macrophages will not be activated and will not produce inflammatory cytokines.

Question 21

How do pathogens activate lamina propria macrophages?

Answer 21

Pathogens, like salmonella, activate macrophages through the Type 3 Secretion System (T3SS) and allow flagellin in, resulting in production of IL1β, which is a strong inflammatory cytokine that can recruit neutrophils.

Question 22

How does shigella flexneri (dysentery) affect the gut?

Answer 22

It penetrates gut epithelium through M cells, invades epithelial cells, and activates NFkB pathway to cause inflammation and protective immunity through recruitment of other immune cells.

Question 23

Does systemic vaccination provide mucosal immunity?

Answer 23

No! Only mucosal vaccination does.

Question 24

What is the benefit of an oral vaccine?

Answer 24

• survives gastric/intestinal degradation
• gains access to Peyer’s patches through M cells
• can activate immune cells with or without adjuvants

Question 25

What are the most potent mucosal adjuvants characterized?

Answer 25

bacterial enterotoxins like cholera toxin (CT) and the heat-labile toxin from E. coli (LT)

Question 26

What is the purpose of mucosal adjuvants?

Answer 26

They are used to break tolerance, as the “default” status of mucosal surfaces is toward immunologic tolerance.

Question 27

Vaccines with CT adjuvant induce primarily a ____ response.

Answer 27

Th2

Question 28

Vaccines with LT adjuvant (specifically, salmonella) induce primarily a ____ response.

Answer 28

Th1

Question 29

What is the largest lymphoid organ system?

Answer 29

MALT (specialized immune system that protects mucosal surfaces); in an adult, it comprises ~80% of all lymphocytes

Question 30

_____% of all Ig-producing cells are in mucosal area, and most are _______ cells.

Answer 30

70-80; IgA plasma

Question 31

The mucosal immune system consists of 2 distinct compartments:

Answer 31

1) epithelium

2) lamina propria

Question 32

What are some effector sites of mucosal immunity?

Answer 32

• lamina propria of GI tract, upper respiratory tract, GU tract
• glands, including mammary, salivary, lacrimal, and sweat