L18: Mucosal Immunity

Question 1

Antigens entering the digestive tract are taken up by specialized mucosal cells called

Answer 1

M cells

Question 2

B cells in the mucosa are selectively induced to produce

Answer 2

dimeric IgA rather than other isotypes.

Question 3

Induction of a response via a mucosal site generally also elicits a

Answer 3

systemic immune response, such that serum antibodies can be detected. This indicates that a mucosal encounter with antigen generates subsets of T and B cells that home to mucosal sites and also to spleen and regional nodes.

Question 4

What are IELs?

Answer 4

A distinct population of lymphocytes, mostly CD8+ T cells are found in the gut epithelium. The function of these cells is still not clear but they may readily kill infected epithelial cells.

Question 5

In a mucosal response to infection, local inflammatory cells are activated via

Answer 5

pattern-recognition receptors,

e.g., TLRs.

Question 6

What’s the most common primary immune deficiency?

Answer 6

Selective IgA deficiency is the most common primary immune deficiency, with an estimated incidence of 1 per every 500 to 1000 persons. The precise characteristics of the deficiency are variable, as some patients have complete IgA deficiency but others have decreased but detectable levels of IgA.

Question 7

Reasons to suspect selective IgA deficiency include

Answer 7

1) a family history of IgA deficiency of agammaglobulinemia,
2) a high incidence of oral infections,
3) frequent respiratory infections, and
4) chronic diarrhea.

Question 8

Autoimmune diseases, including SLE, juvenile rheumatoid arthritis, and thyroiditis, are often associated with

Answer 8

selective IgA deficiency.

Question 9

Immunoglobulin therapy is generally not indicated, for IgA deficiency. Why?

Answer 9

The patient’s normal antibody response can produce anti-IgA antibody in response to IgA treatment. People with a complete absence of IgA may develop allergies or even anaphylactic shock if given gammaglobulin.

Question 10

The predominant immunoglobulin in mucosal secretions is

Answer 10

IgA

Question 11

Serum Ig. What % is IgA? What form is the IgA?

Answer 11

12% IgA class, primarily monomeric.

Question 12

Secreted Ig at mucosal sites – what % is IgA? What form is the IgA?

Answer 12

96% IgA, primarily dimeric IgA in mucous secretions (called secretory IgA, or sIgA)

Question 13

The production of secretory IgA (sIgA) requires what cells?

Answer 13

Plasma cells in the lamina propria and epithelial cells of the mucosa.

Question 14

70-80% of all Ig producing cells, are where?

Answer 14

Mucosal areas! Most of these cells make IgA!

Question 15

What’s the polymeric immunoglobulin receptor (pIGR)?

Answer 15

Located on basolateral surface of mucosal epithelial cells. Helps endocytose the IgA, in prep for secretion

Question 16

Where does the IgA get it’s secretory component from?

Answer 16

the cleaved pIGR!

Question 17

Deficiency in pIGR?

Answer 17

Mice that are genetically deficient for pIgR exhibit the expected decreases in IgA transport.
PIgR deficiency also leads to an increased mucosal leakiness.

Question 18

Barrier function of IgA?

Answer 18

Secretory IgA can bind to bacteria and viruses and prevent their adherence and invasion into mucosal tissues. Secretory IgA can neutralize many viruses in this way, including polio, herpesvirus, coxsackie virus, and rotaviruses. Secretory IgA can also neutralize bacterial toxins at mucosal surfaces

Question 19

What can IgA do to an intracellular virus?

Answer 19

IgA that is internalized by mucosal epithelial cells (via the pIgR) may contribute to intracellular viral inactivation.

Question 20

What if the virus penetrates past the epithelium, into the lamina propria?

Answer 20

Viral particles that complex with dimeric IgA in the lamina propria may be endocytosed and transported out by the pIgR pathway.

Question 21

Passive IgA immunity. 1st thought?

Answer 21

sIgA in breast milk provides passive immunity to the infant.

Question 22

Name 3 pathogens that enter through mucosal surfaces

Answer 22

cholera, HIV, influenza

Question 23

2 advantages of mucosal immunization?

Answer 23

1. Ease of administration (oral)

2. Generates BOTH mucosal and systemic immunity!!! BIG IDEA!

Question 24

2 disadvantages of mucosal immunization?

Answer 24

1. Difficulty in eliciting robust response

2. Response may not be long-lasting

Question 25

Give me an example of a successful oral vaccine

Answer 25

An example of an effective oral immunization is the polio vaccine. Effective nasal spray vaccines for influenza have recently been developed.

Question 26

BONUS: What are some strategies for boosting uptake of foreign antigen at mucosal induction sites?

Answer 26

New strategies for oral immunization include the use of cholera toxin chimeric molecules as well as recombinant avirulent bacteria (e.g. avirulent salmonella expressing S. pneumoniae proteins).

Can also target M cells using bacteria and viruses that preferentially bind M cells or antigen encased in biodegradable particles such as latex.

Question 27

BIG IDEA:

How does the mucosa differentially mount an immunogenic response, versus tolerance?

Answer 27

The key feature that appears to distinguish between the induction of a response and the induction of tolerance is INFLAMMATION.
Antigen encounters that occur alongside inflammation generally illicit an immune response. Antigen encounterd in the absence of inflammation generally induces tolerance.

Question 28

Peptides generally induce tolerance, unless

Answer 28

attached to a mucosal adjuvant, such as cholera toxin.

Question 29

Why do mucosal DC’s turn a blind eye to commensal bacteria? Be specific.

Answer 29

TSLP, PGE2, and TGF-B from commensals suppress DC maturation.

Question 30

Antibiotics disrupt gut floral balance, increasing susceptibility to

Answer 30

C diff