Flashcards in Gut mucosal immunology Deck (16):
Four unique GALT features
Microfold cells, preference for IgA, Paneth Cells, oral tolerance
describe the physical barrier aspect of the GI defenses
Mucus Layer: goblet cells secreting mucin and trefoil factors. Epithelial cells with tight jxns (some Ag's can pass thru). IgA antibodies
BONUS: Name the five types of epithelial cell junctions throughout the body and what they are composed of.
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.
Main antibody type in MALT: what does it require?
IgA. Produced as dimer connected by J chain. Requires epithelial receptor (pIgR) to get transcytosed into lumen
Functions of IgA
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
IgA deficiency: normal course? higher risks? important in screening?
not sever due to compensation by other Ab types. Higher risk of chronic giardiasis, autoimmunity and allergies. Affects Celiac tests
Two cells that produce antimicrobial compounds
Paneth cells: protect stem cells at base of crypt, secrete defensins and lysozyme. Goblet cells: produce trefoil peptides
Describe the Ag uptake process and what cells are involved
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
steps in lymphocyte trafficking
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
What happens after effector cells are activated? Any specific therapy targets
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
Two types of GALT effector cells and their differences
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
Increase in number of IELs is seen in which disease
How is oral tolerance achieved? What could it be used for in the future?
active immune response toward inhibition or anergy. Tolerogenic dendritic cells and Tregs.
Could be harnessed for tx of autoimmune dz
subtypes of dendritic cells and the difference. What regulates the balance
CD103- leads to Tregs and tolerance. CD11b- leads more to Th1 and inflammation. Wnt-beta-catenin regulates
Role of epithelial cells in immunity
physical barrier and Pattern Recognition Receptors (PRRs) for the pathogen associate molecular patterns (PAMPs)