Barrier Immunology in the Gut Flashcards
TH1 cells secrete IFN-y which stimulates class switching to ?
IgG subtypes
TGF-beta and retinoic acid seem to stimulate class switching to
IgA
TH2 cells secrete IL4 and IL5 which stimulates class switching to
IgE
what is the function of IgE
binds to cells with an Fc receptor for IgE triggering degranulation of granulocytes (eosinophils, basophils, mast cells)
IgE is secreted as a ?
monomer
IgA is predominantly found as a ? secreted into the ?
dimer
GI and respiratory tract mucous
what is important function in developing tolerance within the mucosal immune system
IgA
what are major types of innate lymphoid cells (ILCs)
- NK cells
- “resident” ILCs
Type 1 ILCs secretes ?
secrete cytokines such as IFN-y and TNF-a -> “pushes” the barrier into a “Type 1” response and favours the development of Th1 cells
Type 2 ILCs secretes?
secrete cytokines such as IL-4, IL-5, IL-9, IL-13 “pushes” the barrier into a “Type 2” response and favours the development of Th2 cells
Type 3 ILCs secretes?
secrete IL-17, IFN-y -> effective against extracellular bacteria
what are claudins in tight junctions?
trans-membrane proteins that can act as channels for small molecules (paracellular)
what are occludin in tight junctions?
trans-membrane protein, function not clear
what are Junctional adhesion molecules (JAM)?
Trans-membrane protein that may mediate permeability to larger molecules
what are ZO-proteins in tight junctions?
Important in tight junction formation, interact with the cytoskeleton
what are Peyer’s patches?
large collections of lymphoid nodules in the ileum
what are Isolated lymphoid follicles (ILFs)?
MALT nodules without capsules, much smaller than peyer’s patches
what does goblet cells do?
Secrete mucous, which presents a barrier to bacterial invasion
what secretes anti-microbial peptides (AMPs) that prevent bacteria from getting “too close” to the epithelial lining
goblet cells
what else secrete large quantities of AMPs?
paneth cells
what are Very specialized cells present over the surface of Peyer patches and isolated lymphoid follicles (ILFs)
microfold cells
what impairs bacterial mobility and makes it difficult for bacteria to penetrate the epithelial barrier
mucous in the lumen
what is secreted mostly by Paneth cells, mainly toxic against gram (+)-ve bacteria but also seems to have some activity against gram (-)-ves
REG3
what does “unshuffled” IgA mean
the antibody sequence has not undergone affinity maturation – is often broadly specific for a wide range of microbes
what does “shuffled” IgA mean
the antibody sequence has undergone affinity maturation due to Th-B cell interactions
IgA is secreted from plasma cells from 3 major sources:
- ILFS
- Peyer’s patches
- Plasma cells in the mesenteric lymph nodes located around the abdominal aorta
what induces IgA class switching in B-cells via TGF-beta, and CD40L/iCOS interactions – RA plays a role but is not secreted by follicular T cells
T-dependent – follicular T cells (Tfh)
when activated, ILC3 cells secrete?
○ Secrete IL-22 & IL-17, which leads to increased production of AMPs by enterocytes and Paneth cells
○ Secrete factors that induce the full development of Peyer’s patches and ILFs and IgA production
○ Amplify the Th17 response in the gut
Th17 cells can be induced to become either:
- Tfh cells
- Treg cells
what “messes with” our intestinal immune in a complex and multi-step way
Gluten
what is a degradation product of gluten and is resistant to proteolytic degradation by pancreatic enzymes
alpha-gliadin
what does gliadin bind to?
chemokine receptor CXCR3
what does CXCR3 produce and release
zonulin
What happens when zonulin bind to its receptor
disassembly of ZO proteins -> disassembly of tight junctions
what is the adult presentation of celiac disease
- anemia, chronic diarrhea
- bloating, fatigue
- deficiencies in B12 and iron
what is the pediatric presentation of celiac disease
○ Irritability, anorexia, chronic diarrhea, weight loss muscle wasting (malabsorption)
○ Some present with abdominal pain, nausea, vomiting, bloating, or constipation
