Mucosal immunity Flashcards
GI immunity
- epithelial layer w/ mucus
- commensal bacteria
- paneth cells secrete defensins and stuff that keeps pathogenic species at bay
- Peyers patch- important for antigen presentation
M cell– bridge between innate and adaptive immunity. Resp. for uptake of antigens - dendritic cells embedded in the epithelium take up antigens from there and the lamina propria
- mesenteric lymph node
- Plasma cells- differentiated B cells- embedded in the lamina propria secreting antibodies
Mucins
Gastrointestinal mucins are O-linked oligosaccharides
Include secreted and membrane-bound forms (glycocalyx)
Rapid turnover and inducible expression
Epithelial Host Defense- Regulated Expression of TLRs and NLRs
PAMP: pathogen-associated molecular pattern
TLR: toll-like receptor
NLR: Nod-like receptors
Expression of TLRs and NLRs is restricted in the gut and the location of receptors is altered. Furthermore, the functional response of these receptors is biased towards an anti-inflammatory response. The purpose of these alterations is to limit inflammation in the gastrointestinal tract.
Paneth Cells and Defensins
Small cationic peptides (29-34 aa) that contain three intrachain disulfide bonds
Defensins have anti-microbial properties and can act to activate other immune cells
Small bowel
α-defensins produced by Paneth cells (HD5 and HD6)
Neutrophils are also a source of α-defensins
Colon
β-defesin produced by absorptive epithelial cells
C-type lectins- REG3 and REG3β
Peyers patches vs. lymph nodes
. Peyer’s patches are not encapsulted and have a higher percentage of B cells. However, the general structure contains B-cell rich follicles where IgM and IgD-expressing naïve B cells reside. Interspersed between the follicles are T-cell rich zones and the dome region which contains T cells, B cells, DCs and macrophages.
M cells
flattened epithelial cells transport material to the follicular dome areas to interfollicular areas distinguished by ability to pinocytose material transport material in an intact form express MHC class II but no not act as antigen-presenting cells possibly some specificity involved normal flora not transported
deficiency in T cells leads to
widespread inflammation in the gut
Homing signals
α4β7 on lymphocytes binds MAdCAM-1 on postcapillary venule endothelial cells in the gut lamina propria
Chemokine receptor CCR9 on lymphocytes binds the chemokine ligand on intestinal epithelial cells (in small intestine)
Chemokine receptor CCR10 binds chemokine CCL28 expressed by colon and breast tissue
Dendritic cells promote the expression of α4β7 and CCR9 through retinoic acid synthesis (mechanism for this transition is unknown). Only DCs in the gut express retinal dehydrogenases (RALDH) which is necessary for the synthesis of retinoic acid from vitamin A.
IgA Function
Protective role of secretory-IgA (s-IgA)
neutralize biologically active antigens
viruses, toxins and enzymes
prevent uptake of antigens by the intestinal tract
inhibit adherence of bacteria to epithelial surfaces
Enhancement of innate immune factors
IgA structure
Serum IgA
Physiologic role of IgA in the blood is unclear
humans is mainly monomeric
Amount transported from serum to secretions is very low
Does not fix complement
will not induce an inflammatory response
Mucosal antigen gets into circulation will not induce a sytemic inflammatory response
Prevents colonization without inflammation
Allows for clearance of circulating antibody antigen complexes without inducing systemic inflammation
Kupffer cells in liver filter out IgA-antigen complexes
what’s important about IgA?
does not induce inflammation
Cell-mediated Immunity
Intraepithelial cells are mostly CD8+ T cells
10% of intraepithelial cells are γδ T cells
Intraepithelial cells have a limited T cell repertoire
Lamina propria cells are mostly CD4+ T cells
CD4+ T cell Subsets
Th17
- Murine models indicate that Th17 cells play a role in colonization and protection of the gut
- IL-17 and IL-22 characteristic cytokines
Th2
Th2 cells protect against helminthic infections
- IL-4 and IL-13 characteristic cytokines
Regulation of Immunity in the GI Tract
The lamina propria has a higher percentage of FoxP3+ Tregs than any other tissue in the body
CD103+ DC, retinoic acid, and TGF-β all play a role in the development of Tregs
TGF-β, IL-10, and IL-2 are characteristic cytokines
commensal bacteria vs. pathogenic bacteria
The human gut hosts trillions of microorganisms referred to as the microbiota
Beneficial species include Lactobacillus spp., Bifidobacterium spp., and Escherichia coli Nissle 1917
The is evidence showing beneficial bacteria can protect against pathogenic species including: Salmonella Typhimurium and Clostridium difficile
