The Mucosal Immune System (AKA Barrier Immunity) Flashcards
What does the mucosal tissue make up in the human body?
makes up largest ‘exposed’ surface area of the human body
What do majority of infections target
the mucosal tissues
Why is the mucosal tissue easy to infect?
-surface exposed (its job is to absorb things)
-thin membranes (to absorb things)
-largest surface area
-ALWAYS encountering foreign substance
Explain the two versions of organization of the intestinal immune system
-organized (immune cells create organized structures)
-peyer’s path (small intestine)
-isolated follicle (small & large)
-lamina propria
-scattered
-effector cells
-lamina propria & epithelial
What is the Mesenteric lymph node
-largest lymph nodes (activation of adaptive immunity
-can become inflamed (w/infection)
-differentiates separately from the other lymph nodes
What does the Peyers’ Patch do
absorb nutrients (right under epithelial cells
What are microfold (M) cells
-a way to sample what is in gut. To see if its good or bad
-antigen transported across M cells is presented by dendritic cells to T cells
What is Transcytosis
-both endo- & exo-cytosis
-basically, endocytosis on one side, exocytosis on the other
-important for epithelial cells (antigen uptake (M-cells)) (IgA EXPORT!!)
What is the BIG downside to M-cells
-does not secrete mucus (thinner mucus layer @ Peyer’s Patch) therefore more likely to get infected
-transcytosis can be co-opted
-Shigella uses M-cells to bypasses defenses, can survive macrophages, now moves to other cells!
How do DC’s and macrophages uptake antigens
-DC can move to Peyer’s patch to prime naive T cells (by acting as APC)
-DC & macrophage can display for effector T cells at site (if they don’t move)
Name the 6 routes for intestinal antigen uptake
-nonspecific transport across epithelium
-FcRn-dependent transport
-Apoptosis-dependent transfer (hole in intestine where antigen can freely enter)
-Antigen capture by macrophage (good way, doesn’t break barrier and apoptosis of pathogen before bringing antigen in)
-Uptake via goblet cells
-Capture by intraepithelial dendritic cell (can exist in epithelial layer)
What happens once T cells are primed (DC brought antigen to Peyer’s Patch, now activation of T cell)
-T cells express gut-specific chemokine receptors/adhesins
-protect ENTIRE gut lining
-KEY: not moving back to where infection: b/c everything is moving, infection is in new location
How do Th cells drive IgA production by B cells
-specifically drive class-switching to IgA (dimer joined by J-chain, generally found in mucus)
-Epithelial ells express pIgR (binds IgA and Transcytosis)
-Secretory component binds mucins (holds IgA to mucosal lining
What is the secretory component
piece of protein that bind IgA _ mucins holding IgA to mucus
What are the 4 roles do secreted IgA serve
-secreted IgA on the gut surface can bind and neutralize pathogens and toxins
-IgA is able to bind and neutralize antigens internalized in endosomes
-IgA can export toxins and pathogens from the lamina propria while being secreted
-Binding of IgA to Dectin-1 on M cell allows transport of antigen to DC-SIGN* dendritic cell (delivered through transcytosis)
What is intraepithelial lymphocytes (IEL)
Basically T-cells, but inside epithelial linging
-two types A (inducible) and B (natural- always present)
What is epithelial cells’ key role
-balances response to infection by fighting infection without attack microbiome
-own TLR’s and NODs
-make variety of cytokines for specific infections
-TLR for bacteria: bind cell wall
-can distinguish good from bad based on location
What is mucosal tolerance
-developing ‘nonresponsiveness’ to a specific antigen
-type of peripheral tolerance (non in bond marrow/thymus
What is the role of Treg’
-suppress immune responses, specifically against self
-can even suppress T cells on the same APC
What is the mechanism of Treg immunosuppression
-First, activated by TCR binding to MHC’s on APC (activate Treg and localizes to antigen site)
-BUT this leads to very different outcomes (releases anti-inflammatory cytokines, inhibits APC’s activation of other effector T cells, kills effector T cells and injibit effector T cell metabolism)
What is the key TF for Treg development
-FoxP3 (marker of Tregs and important for activation
What happens when there is mutations in FoxP3
-lead to IPEX
-immune dysregulation
-main symptom: intractable diarrhea
What is Interleukin-2
general survival signal
What is TGF-beta
immune suppressing cytokine
-drives Treg differentiation
