Immune System & GI tract Flashcards
(30 cards)
what’s the main component of mucosa immunity?
MALT - mucosa associated lymphoid tissue (also have bronchus, nasal and gut (best understood) ALTs)
what are 3 of the challenges of the GALT?
- Large area to protect (> 400 m2)
- exposed to foreign antigens from food
- exposure to foreign antigens from colonic bacteria
Pts who have their tonsils removed show a diminished response to what?
Diminished IgA response to polio
what 2 unspecific IR things protect the epithelium from damage?
- mucus (produced as mucin by goblet cells)
2. AMP (antimicrobial proteins; like a-defensins; paneth cells, in base of crypts)
what are 3 structural features of GALT?
- scattered lymphoid cells (dendritic cells)
- isolated organized lymphoid follicles
- Peyer’s patches (a part of organized lymphoid follicles)
what are M cells and what do they lack?
specialized cells that line the dome region of peyer’s patches and take up antigens by endocytosis and phagocytosis & releases it via transcytosis to present them to the dendritic cells to present it to peyer’s patches T cell region or mesenteric LN.
lack microvilli and mucus
In the GALT where are dendtric cells located?
DCs are in organized lymphoid tissue (like Peyer’s patches) and scattered lymphoid cell compartments. They can uptake antigens and migrate to mesenteric LNs to present to T cells
what are the 2 ways to activate the immune system through the gut?
- antigen presentation in peyer’s patches
2. antigen presentation in mesenteric LNs
where’s the lamina propria in the gut and what’s it made of?
Layer of CT (myofibroblasts) directly underneath the mucosal epithelium where immune cells (T cells - CD4 & 8, MO, eosinophils, mast cells, plasma cells - producing IgA) are located.
CD8 cells: effector memory T cells are more active, they have selective chemokine: chemokine receptor interactions in mucosa sites via expression of CCR9
What separates the epithelium from the lamina propria? what cells are located in the epithelium?
its separated from the epithelium (CD8aa T cells - central memory T cells: ) by thin layer of basement layer
where is a4B1 T cell integrin induction homed to?
periphery
what does a4b7 T cell integrin bind to?
mucosal vascular addressin (MAdCAM-1) expressed on the endothelial lining of bvs of the gut
what explains the preference of HIV for GALT?
lymphocytes home to the gut by a4B7 integrin molecule which is also a co-receptor for HIV
what in the GALT gets severely and selectively depleted in the 1st weeks post HIV infection?
what does the rates of replenishment determine?
CD4 CCR5 T cells
the rates of replenishment determines when AIDS will develop
what’s the main function of B cells in GALT? what mediates this? Where do they home?
class switch to IgA (then become plasma) by cytokine TGF-B plasma cells home to the lamina propria using CCR9 and a4B7
what’s the function of IgA GALT
IgA secreted onto gut surface and binds/neutralizes pathogens/toxins or exports them from lamina propria while be secreted. it also binds/neutralizes anitgens to intenernalize them in via poly-IgA receptor
how do DC in GALT becoming activated in response to enteric pathogens?
what kind of response does it create?
either directly via DC TLRs or indirectly thru activation of epothelial cells intracellular vesicle TLRs or their NOD1 & 2 cytosolic leading to NF-kB activation to activate DCs
induces Th1 and/or 2 response
where are the TLRs and NOD1/2 located in GALT epithelial cells?
TLRs are in the vessicles
NOD1/2 are in the cytosol
What are the 3 concepts that may explain if the GALT is inappropriately activated in inflammatory disease processes of the gut?
- mutations in NOD
- deregulation of IEL (intraepithlium lymphocytes)
- deregulation of regulatory T-cells
describe the T cells in the lamina propria
CD4 T cells, effector memory type = activated Home via CCR9 & a4B7 produce INFy (controls T cells), IL5 (controls worms) & IL10 (involved in producing regulatory cells)
describes the T cell in the epithelium
CD8 T cells are effector memory type = activated
home via CCR9 and aEB7 to the epithelium
produces INFy
a subset express a:a homodimer of CD8, indicating a higher affinity for non-classical MHC I on epithelial cells (likely causes down regulatory properties rather than activating)
what GALT defect can be assoc w/ crohn disease?
mutated NOD so can’t make antimicrobial proteins in paneth cells
what initates vs sustains crohn disease?
Initate: injury to epithelium
Sustained: inappropriate immune response
what happens to the # of CD8aa (natural IELs) and CD8ab (induced intraepithelium lymphocytes) as we age?
CD8aa (natural IELs): decreases b/c have finite # of them
CD8ab (induced IELs): increases, they activate things
