Mucosal Immunity

Question 1

70-80% of all immunoglobulin producing cells in the body are located within what tissue, and what is the dominant Ig produced?

Answer 1

70-80% are located in the tissues of the mucosal immune system, and they primarily release IgA

Question 2

Antigens that enter the digestive tract are taken up by what cells?

Answer 2

M cells

Question 3

What do M cells do with antigen?

Answer 3

M cells internalize the antigen and transport it across the epithelium where antigen can be take up by APCs such as DCs.

Question 4

What stimulates the formation of M cells?

Answer 4

M cells are formed in mucosal epithelium in response to signals from lymphocytes

Question 5

How do DCs take up antigen from the GI lumen?

Answer 5

Antigen is captured from the lumen by DCs that extend across the epithelial layer.

Question 6

What happens to antigen captured via DCs or M cells?

Answer 6

They are presented to lymphocytes located in specialized mucosal immune tissues, such as Peyer’s patches in the GALT

Question 7

How to M cells take up antigen?

Answer 7

Endocytosis and phagocytosis

Question 8

How is an immune response initiated after antigen is taken up by M cells in the gut?

Answer 8

Antigen is bound by DCs and presented to T cells which are then activated

Question 9

Describe the Fc- mediated uptake of antigen in MALT tissue.

Answer 9

If there are already antibodies available to coat a bacterial pathogen, Fc receptors on the enterocytes of the gut can bind and take up the pathogen - it is transported to DCs

Question 10

What happens to T cells that are activated in Peyer’s patches?

Answer 10

They migrate to the lamina propria of the small intestine

Question 11

What does it mean that lymphocytes have tissue-specific homing receptors?

Answer 11

There are receptors/signals that attract lymphocytes specifically to the mucosa

Question 12

Where are most of the MALT cells located with respect to the epithelial layer?

Answer 12

They are located just below the epithelial layer in the subepithelial layer (lamina propria), although there are some specialized areas that have intra-epithelial lymphocytes

Question 13

Intraepithelial lymphocytes are what type of cell?

Answer 13

CD8+ T cells

Question 14

Are peyer’s patches the initiator or effector sites? What does that mean?

Answer 14

Peyer’s patches are initiator sites- they are the site of antigen capture, but the response does not happen locally.

THe plasma cells all end up in the lamina propria (not the peyer’s patch)

Question 15

How do the inductor cells get to the effector locations?

Answer 15

Following induction/antigen uptake, activated cells go into the lymphatic system, dump into the subclavian vein/into the blood stream, and are eventually honed to the effector sites of the mucosal tissue via tissue-specific homing receptors/molecules

In most cases, they go back to sites similar to where they were (i.e. gut usually goes to the gut, but occasionally they could go to the lung)

Question 16

B cells in MALT selectively produce which antibody?

Answer 16

dimeric IgA

Question 17

Which immune cells are particularly important in the gut?

Answer 17

T cells, specifically CTLs

Question 18

Does mucosal immunity result in systemic immunity?

Answer 18

Yes- this is a big advantage of mucosal immunity

Question 19

What is the job of intraepithelial lymphocytes?

Answer 19

To kill infected cells (virally infected cells) by perforin/granzyme and Fas-dependent pathways

Question 20

WHat is the first line of mucosal defense? How is this accomplished?

Answer 20

Epithelial cells: they provide innate defense against most pathogens

The epithelial cells activate NFkappaB, which leads to the synthesis of pro-inflammatory cytokines which leads to destruction of the pathogens

Question 21

Name two highlighted organisms that enter through the M cells and lead to infection of the mucosa

Answer 21

Shigella and Salmonella typhimurium

Salmonella enters through M cells and can kill them- requires a DC to take it up and start and immune process

Shigella: enters through M cells and infects other epithelial cells- requires activation of pro-inflammatory cytokines in order to defend and kill the pathogens

Question 22

How could you be IgA deficient?

Answer 22

Genetic reason –> no switch region/ no IgA forms properly

Question 23

How common in IgA deficiency?

Answer 23

1:500- 1:1000

Question 24

What are the clinical problems seen with IgA deficiency?

Answer 24

1) Some people have no problems

2) Some people are at risk for increased mucosal infections

Question 25

What is the difference between IgA1 and IgA2?

Answer 25

Different by the constant region of the heavy chain- they differ by a few amino acids -

Both found as dimers in the mucosa- they both have a secretory component characteristic of IgA

Question 26

How does IgA exit the lamina propria and get into the lumen of the gut?

Answer 26

Poly-Ig receptors- they can bind dimeric IgA and pentameric IgM and endocytose the Ig and release it on the lumenal side - it takes part of the receptor with it, which is the secretory component!

Now the IgA is in the lumen and can protect against various pathogens.

Question 27

Passive immunity is provided to babies through what class of antibody in breast milk?

Answer 27

secretory IgA

Question 28

What are the advantages of mucosal immunization?

Answer 28

Easy to administer (orally)

Provides systemic and mucosal immunity

Question 29

What are the problems with mucosal immunity?

Answer 29

1) short-lived: you don’t have lots of germinal centers to general plasma memory cells
2) It’s hard to generate a good immune reaction because of tolerance- ORAL TOLERANCE

Question 30

Can systemic vaccinations provide mucosal immunity?

Answer 30

No- only mucosal vaccinations cause both mucosal and systemic immunity

Question 31

What is required for the induction of mucosal immunitY?

Answer 31

Inflammation