Mucosal Immunity (Davis) Flashcards
What’s mucosal immunity referred to as?
regional immunity
How is the mucosal immune system anatomically distinct?
- diff. antibodies
- diff. types of T cells
- includes B-1 and MZ B-2 B cells
How is the mucosal immune system functionally distinct?
- diff. physiological activities
- diff. mechanisms of antigen uptake
- diff. means of inducing (inductive sites) & carrying out immune functions (effector sites)
(T/F) In mucosal immunity, antigen has to cross epithelial barriers
TRUE
what are inductive sites?
where antigen is taken up, presented, lymphocytes are activated, & B cells undergo isotype switching/SHM
(T/F) Clonal proliferation does NOT occur at inductive site
TRUE
What are effector sites?
lymphocytes home back to these & secrete effector molecules
Compartmentalization is achieved:
through strong lymphocyte homing for mucosal tissues (large homing effect)
(T/F) most of our lymphocytes are in mucosal tissues have more deltagamma T cells more than alphabeta T cells
TRUE
The independent fetal development of what makes for a distinct immune response?
mesenteric LN’s & Peyer’s patches
(inductive sites) where is the immune response is induced?
O-MALT
4 anatomical areas of O-MALT?
- GALT
- NALT
- BALT
- RALT
D-MALT contains what sites?
effector sites: where antibodies are secreted
What is spread throughout mucosal tissues and contains lamina propria, salivary glands?
D-MALT
Lamina propria is..?
underlying connective tissue that contains blood vessels, as well as specialized cells
(innate) the gut mucosa protects us from infxns by:
- mucus
- glycocalyx
- antimicrobial peptides
- C-type lectins
- localized PRRs
- mucin decoy molecules
- ILCs
- inhibition of inflammation
what induces the production of mucin molecules?
IL-5, IL-13
how does mucus help us?
thick layer keeps pathogens from reaching surface of gut epithelium
how does the glycocalyx act as a physical barrier?
prevents microbes from making contact w/ epithelial layer
(T/F) antimicrobial peptides affect our natural gut mucosa
FALSE; they do not affect
the main antimicrobial peptides in the small intestine are?
alpha defensins- produced by paneth cells
main antimicrobial peptides in large intestine are?
B-defensins- produced by absorptive epithelial cells
In response to inflammation, neutrophilic granules also contain what to help protect the colon?
alpha-defensins
What disease correlates with a defect in defensin production?
Chron’s disease
Paneth cells secrete ____ called regenerating islet-derived proteins (REG III)
C-type lectins
What do REG III lectin proteins do..?
- block bacterial colonization of the mucosal epithelial surface
- have bactericidal effects against G+ bacteria
TLR & NOD proteins are expressed only in certain cells/areas of the gut. they are activated upon what..?
upon bacterial invasion
TLR5 recognizes ___ and is expressed only on the basolateral surface of intestinal epithelial cells
flagellin
TLR signaling results in the secretion of..?
increased defensins, REG III protein lectins & IgA
TLR and NOD proteins are examples of?
localized PRRs
Mucin decoy molecules are shed from intestinal epithelial cells and bind to what..?
binds to adhesin proteins on the intestinal bacteria- this blocks them from binding to intestinal cells
Innate lymphoid cells secrete cytokines in response to ___ (ILC-activating cytokines IL-1B)
alarmins
Production of what increases production of mucus or defensins which enhance fxn of tight junctions?
Il-17, IL-22, IL-23
Some gut macrophages have unique phenotype that secrete which anti-inflammatory?
IL-10
(adaptive) The gut mucosa protects us from infxns by:
- IgA, IgG, IgM,
- specialized anatomy
- strong homing/lymphocyte trafficking
Isotype switching to IgA is induced by?
induced by TGF-B
B cells are activated in ____ undergo isotype switching to IgA
Peyer’s patches
Plasma cells home back to the ____ where they secrete pIgA
lamina propria
The pIgA is taken up (via J chain) by the ___ and transcytosed into the lumen (SIgA)
pIgR
___ plays an important role in mucosal immunity of the oral cavity and minor role in the GI tract
IgG
_____ pentamer w/ a J chain is transcytosed via pIgR and is an adaptive immunity feature
IgM
Specialized anatomy that’s part of the adaptive immunity feature include:
- peyer’s patches
- lamina propria
- salivary glands
What’s part of the O-MALT, found throughout the GI tract and is the inductive site of the mucosal immune response in the gut?
Peyer’s patches
In the Peyer’s patches, antigens enter via transcytosis through _____
M cells
The inductive site in the Peyer’s patches are covered by the _____ area which lies beneath the FAE and contains large #’s of APCs & T follicular helper cells
dome area (mantle zone)
(peyer’s patch) Under the dome area is the corona, is where what is located?
where the naive B cells are located
what is not organized into specialized lymphoid structures- D-MALT and is where most gut pIgA is produced?
Lamina propria
what is populated with memory mIgA+ B cells, IgA-secreting plasma cells, memory Th cells, DCs, macrophages, mast cells ?
lamina propria
____ is part of D-MALT and is the main source of IgA in the oral cavity
Salivary glands
What form IgA is produced in the salivary glands?
dimeric (pIgA)
what epithelium expresses class II HLA-Dx molecules & goblet cells; it’s also organized into villi & crypts?
mucosal epithelium
mucosal epithelium have ___, ___, & _____ interspersed b/w & among the epithelial cells
lymphocytes, DCs, & macrophages
Mature, differentiated T cells that interspersed among the mucosal villous epithelial cells are _____
intraepithelial lymphocytes
what type of memory CD8+ CTLs?
aB memory cells
When a mucosal epithelial cell becomes infected, injured, or stressed, it expresses which certain protein on it’s basolateral surface..?
MIC-A/MIC-B (stress proteins)
___ see stress proteins and kill cell
IPLs
What’s a specialized epithelial layer that covers the Peyer’s patches and contains M cells..?
Follicle Associated Epithelium (FAE)
what type of specialized antigen uptake cells of the FAE overlying O-MALT tissues?
M cells
main fxn of M cells?
uptake of luminal antigens
- actively pinocytic
Ingested antigen is transcytosed ____
intact (transcytosis)
Basolateral surface is invaginated, pockets contain:
DCs, naive lymphocytes
APCs take up antigen & present it to T cells in what area of the peyer’s patches?
dome area
In an H. pylori infxn, what happens to mucus production?
it decreases
Where are goblet cells located?
located at top of villi and in FAE
- in large and small intestines
Paneth cells secrete ___
antibacterial peptides
Paneth cells contains granules with..?
lysozyme, defensins, & phospholipase enzymes
Main differentiating separates the mucosal immune system from the systemic is..?
homing of activated lymphocytes
How is antigen uptake different in mucosal immunity?
- must be taken across epithelial barrier by active vesicular transport
- not phagocytosed by an APC until after it crosses the barrier
- APC does NOT migrate to LN
- antigen uptake is restricted
