Gut mucosal immunology

Question 1

Four unique GALT features

Answer 1

Microfold cells, preference for IgA, Paneth Cells, oral tolerance

Question 2

describe the physical barrier aspect of the GI defenses

Answer 2

Mucus Layer: goblet cells secreting mucin and trefoil factors. Epithelial cells with tight jxns (some Ag’s can pass thru). IgA antibodies

Question 3

BONUS: Name the five types of epithelial cell junctions throughout the body and what they are composed of.

Answer 3

Tight jxn (zonula occludens): claudins and occludins. Adherens jxn (zonula adherens): connects actin cytoskeletons via cadherins. Desmosome (macula adherens): keratin. Gap jxn: connexon channel proteins. Hemidesmosomes: connects keratin in basal cells to BM.

Question 4

Main antibody type in MALT: what does it require?

Answer 4

IgA. Produced as dimer connected by J chain. Requires epithelial receptor (pIgR) to get transcytosed into lumen

Question 5

Functions of IgA

Answer 5

Keeps commensal bacteria in mucus layer. Neutralizes toxins. Binds to pathogens and neutralizes them in epithelial cell endosomes. Transport antigens from Lamina propria into lumen

Question 6

IgA deficiency: normal course? higher risks? important in screening?

Answer 6

not sever due to compensation by other Ab types. Higher risk of chronic giardiasis, autoimmunity and allergies. Affects Celiac tests

Question 7

Two cells that produce antimicrobial compounds

Answer 7

Paneth cells: protect stem cells at base of crypt, secrete defensins and lysozyme. Goblet cells: produce trefoil peptides

Question 8

Describe the Ag uptake process and what cells are involved

Answer 8

At induction site: M cells, peyer/s patches, dendritic cells, epithelial cells (MHC class II). M cells bring antigens across to basal side to dendritic APC which is in a pocket with lymphocyte to which it presents the Ag. Dendritic cells and goblet cells can also do lumenal sampling via various mechanisms

Question 9

steps in lymphocyte trafficking

Answer 9

Ag sampling at inductive site in Peyer’s patch. Migration (of B cells and T cells) to mesenteric lymph node as either tolerant or prime CD4 cells. Re-circulation back to lamina propria and intra-epithelial cell compartment of gut

Question 10

What happens after effector cells are activated? Any specific therapy targets

Answer 10

they selectively up-regulate chemokine and adhesion molecules for homing. A4beta7 binds MADCAM-1 on mucosal cells and could be a target for IBD therapy

Question 11

Two types of GALT effector cells and their differences

Answer 11

Lamina propria cells: IgA plasma cells, activated B cells, CD4 T-cells, APCs, innate lymphoid cells.
Intraepithelial lymphocytes: mostly CD8 T-cells, function varies according to location in GI tract

Question 12

Increase in number of IELs is seen in which disease

Answer 12

celiac

Question 13

How is oral tolerance achieved? What could it be used for in the future?

Answer 13

active immune response toward inhibition or anergy. Tolerogenic dendritic cells and Tregs.
Could be harnessed for tx of autoimmune dz

Question 14

subtypes of dendritic cells and the difference. What regulates the balance

Answer 14

CD103- leads to Tregs and tolerance. CD11b- leads more to Th1 and inflammation. Wnt-beta-catenin regulates

Question 15

Role of epithelial cells in immunity

Answer 15

physical barrier and Pattern Recognition Receptors (PRRs) for the pathogen associate molecular patterns (PAMPs)

Question 16

how is epithelial expression of TLR important? what happens if there is a defect?

Answer 16

recognizes pathogens and induces response. If you can’t control TLRs you get excess inflammation. Susceptibility genes: mutation in NOD2 (TLR modulator gene) leads to Crohns dz