Wk 4 Mucosal Immunology

Question 1

What epithelial cells have barrier functions?

Answer 1

1. Villi (increased SA)
2. Crypts (stem cells, tissue regeneration)
3. IECs: glycocalyx
4. globlet cells (mucus)
5. Paneth cells (defensins)
6. Tuft cells (enhance Th2, anti-helminth response)

Question 2

Intestinal epithelial cells

Answer 2

=enterocytes

Question 3

Parts of intestinal enterocytes

Answer 3

Question 4

How is MALT divided?

Answer 4

1. GALT -GI associated: PP, appendix
2. BALT - bronchial
3. NALT - nasopharyngeal
4. mammary glands
5. salivary and lachrymal glands
6. genitourinary tract

Question 5

What is the Peyer’s Patch?

Answer 5

PP

1. PPs: lymphoid aggregates with no capsule.
2. Located in the ileum.
3. B cell zone with surrounding T cell zone.
4. CD4+ T cells, DCs, B cells, plasma cells
5. Antigen sampling: M cells.
6. PPs drain to mesenteric LNs.
7. IgA- producing plasma cells.

Question 6

What are M cells?

Answer 6

-microfold cells
* No villi or glycocalyx, do not secrete mucus
* Often lack microvilli, instead have microfolds
* Basal membrane is extensively folded
* cluster near Peyer’s Patches

Question 7

How do M cells deliver antigens?

Answer 7

Via transcytosis
* M cells transport antigens from the lumen to the Peyer’s Patch
* Antigen taken up by DCs, presented to CD4+ T cells
* Antigen taken up by B cells
* Induction of IgA response

Question 8

What are 2 places gut dendritic cells hang out?

Answer 8

1. Within PPs- obtain antigen by transcytosis from M cells
2. Within the lamina propria they obtain antigen via: Ig-mediated transport, IEC
   apoptosis, protrusions in between tight junctions.

Question 9

Make slide

Answer 9

Question 10

What cell types are in the lamina propria?

Answer 10

• Activated T cells: Th1, Th2, Th17, Treg
• Dendritic cells (drain to lymph nodes)
• IgA-secreting plasma cells
• Innate cells: macrophages, Mast cells

Question 11

What cells are found in the gut epithelium?

Answer 11

• Intra-epithelial lymphocytes (IELs)
• CTL-like

Question 12

What are the 2 functional subgroups of dendritic cells?

Answer 12

1. Effector DCs - stimulate effector T cell responses
2. Regulatory DCs stimulate Treg responses

Question 13

What is the role of regulatory DCs?

Answer 13

help maintain tolerance to food antigens and commensal bacteria.
* Metabolize Vitamin A into retinoic acid (RA) using retinol dehydrogenases.
* Secretion of RA by these DCs allows them to induce the formation of Tregs
* Does diet influence gut immunity? IBD?

Question 14

What is the predominant class of immunoglobulins in most of the mucosal secretions?

Answer 14

IgA
-exceptions are vaginal and lung secretions where IgG dominates

Question 15

What are 3 roles of IgA?

Answer 15

1. neutralize toxins
2. prevent colonization
3. deliver antigens to lamina propria

Question 16

How is IgA transported to lumen?

Answer 16

Transcytosis

Question 17

What are characteristics of IgA deficiency?

Answer 17

• IgA deficiency is relatively common
• autosomal dominant with incomplete penetrance
• usually asymptomatic (80-90%), other isotypes may compensate
• may result in mild increase in susceptibility to infection
• rare anaphylactic reaction to blood transfusions (due to IgA in donor blood)
• increased incidence of autoimmune disease, for reasons unknown

Question 18

What antibodies are transferred maternally?

Answer 18

IgG passively transplacentally
transent low IgG after birth

Question 19

What Ig is secreted into milk during lactation?

Answer 19

• B cells and plasma cells are recruited into the lactating breast (chemokine-mediated).
• Systemic Ig can also infiltrate mammary gland.
• Ig is shuttled into breast milk via transcytosis.
• Mostly IgA, some IgG and IgM.

Question 20

What is the neonatal receptor for IgG?

Answer 20

FcRn

Transcytosis of IgG across placenta, and into lung: FcRn
Bi-directional transcytosis via FcRn (neonatal Fc receptor)
Transport IgG to respiratory, female genital tract lumens (dominant Ig) Transport across placental barrier in utero.