Lecture 14: Specialized Immunity at the GI epithelial barriers Flashcards
Patients with severly reduced C3 levels tend to have
increased number of severe bacterial infections
The membrane IgM and IgD on the surface of
are identical except for their CH chains
The ____ contains blood and lymphatic vessels, and mucosa-associated lymphoid tissues
Lamina propria
Specialized ______ cells deliver Ags across the epithelial barrier of the gut directly to subepithelial DCs that then present Ag locally in adjacent mucosal T-cell areas
Microfold (M) cells
which has a larger tolerance to bacteria the small or large intestine
Large intestine (makes sense becaue it has more commensals)
Epithelial cells produce anti-microbial peptides _____
defensins
Most immune responses are induced by PRRs but, instead, these responses can be ______ in the gut
Anti-inflammatory actions
Physical/chemical barrier of the gut is formed by _____, which prevent microbes from contacting epithelial cells
Mucins
Mucins inclued secred and cell surface _____
glycoproteins
The secreted mucins form what two layers of gel
- outer less-dense layer that is normally colonized by bacteria
- a denser inner layer that is bacteria-free
- (note both layers contain anti-microbial substances are produced by the epithelial cells aka produced Defensins)
The apical surface of GI epithelial cells is coated with membrane-bound mucin proteins called the ____
glycocalyx
Mucins are replaced by newly synthesized molecules every ____ to ____ hours
6-12 hours
What cytokines can increase mucin production
- IL-1
- IL-4
- IL-6
- IL-9
- TNF
- IFNalpha
- elastase (from neutrophils)
- microbial adhesive proteins
- (note that these can not only icrease production but can alter mucins glycosylation which are thought to increase barrier function against pathogens)
____ and ____ cells constitutively produce defensins to provide innate protection against luminal bacteria
Epithelial and Paneth cells
Are encapsulated bacteria more resistant to defensins
yes
In the small bowel, the major defensins are the _____ produced by paneth cells
Alpha-defensins
The ____ defensins are produced by epithelial cells in the colon
Beta-defensins
Defects in defensin production by epithelial cells is linked to ____ disease
Crohn’s disease, a chronic inflammatory disease that can involve the entire GI tract
Commensal bacteria may express lipopolysaccharide, peptidoglycans, CpG DNA, and flagellin. Thus there are stringent control mechanisms to limit TLR-induced proinflammatory responses to commensal bacteria. Such as
- TLR signaling increases barrier function but NOT inflammation
- TLR5, which recognizes bacterial Flagellins, is exclusively expressed on the basolateral surface and thus it will be accessible only to bacteria that have invaded through the barrier
- The NOD-like receptors for flagellins are expressed in the cytosol of intesstinal epithelial cells
- NOD-like receptors will activate inflammatory responses ony when pathogenic bacteria or their products gain access to the cytosol
The dominant protective cell-mediated immune response of the gut consists of _____ cells
Th17
A major mechanism for controlling responses in the gut is the activation of
Treg cells
The ___ cells are specialized intestinal epithelial cells found in the small bowel epithelium overlying the Peyer’s patches and lymphoid follicles in the lamina propria
M cells
In the Peyer’s patches and mesenteric LNs, DCs convert dietary Vitamin A into ____ (induced by thymic stromal lymphopoietin, TSLP)
Retinoic acid
When Naive B or T cells are activated by Ag in the Peyer’s patches and mesenteric LNs, they are exposed to Retinoic Acid that induces the expression of ____ and ___. Which leads to
- chemokine receptor CCR9 and the integrin Alpha4beta7 on the effecotr B and T cells
- The effector lyphocytes enter the circulation and home back into the gut lamina properia because the chemokine CCL25 (the ligand for CCR9) and the adhesion molecule MadCam (the ligand for Alpha4beta7) are dispayed on lamina propria endothelial cells
