Mucosal Immunity Flashcards
Amount that microvili increase the intestinal surface area by.
30-fold.
Factors secreted by enterocytes
TGF-beta, chemokines, defensins
Factors secreted by goblet cells
Mucins, lysozyme, lactoferrin
Factors secreted by paneth cells
Defensins
Paneth cell location
Base of vili
Surface area of small intestine
250 square meters
Number of resident bacterial species in GIT
700 - 1000
Number of bacteria in GIT
~10^14
Glycocalyx
Mucus layer that associates with glycoprotein and polysaccharide complex.
On enterocytes.
Keeps bacteria away from epithelial surface.
Innate defence mechanisms of the gut
Peristalsis
Acid
Glycocalyx
Tight junctions between cells
Regular replacement of enterocytes
Cytokines and chemokines secreted by cells
Lymphocytes, macrophages, dendritic cells
Spleen
Receives antigens from the blood.
Part of systemic immune system.
Mucosal lymphoid tissues
Tonsils, adenoid, appendix, Peyers patches, large intestine.
Mucosal immune system antigen access
Sampled directly from gut lumen.
Scattered lymphoid cells
Effector sites
Organised lymphoid tissues
Inductive sites
Blood vessels that run through Peyers patches, mesenteric lymph nodes.
High endothelial venules
Cells that sit on top of Peyers patches
M cells
Area beneath epithelial layer on Peyers patches, contains dendritic cells
Sub-epithelial dome
Where Peyers patches drain to.
Mesenteric lymph node.
Cells from which M cells have differentiated
Endothelial cells
Features of M cells
No microvili.
Don’t secrete mucus.
Controlled uptake of antigens.
Transport antigens to sub-epithelial space.
Do not express MHC class II
Located directly over organised lymphoid tissue.
Location of M cells
Directly over organised lymph tissue in mucosal immune system.
Classes of MHC on M cells
MHC class I. No MHC class II.
Two methods of antigen access to mesenteric lymph nodes
1) Via microfold cells.
2) Via dendritic cells, which migrate from vili to MLN.
Mucosal dendritic cell specialisations
Secrete cytokines to skew T response to Treg, Th2 (TGF-beta).
Bias B cell isotype to IgA.
Induce alpha 4 beta 7 expression on activated lymphocytes.
Integrin alpha-4 beta-7 ligand.
MAdCAM1
Activation of naive lymphocytes occurs in:
Peyers patches - APCs take up antigen delivered by M cells.
Mesenteric lymph nodes - Dendritic cells migrate from Peyers patches, lamina propria, present antigens.
APC uptake of antigens occurs in:
Lamina propria - DSs directly sample lumen contents.
Peyers patches - DSs take up antigens let in by M cells.
Anti-mesenteric border
Opposite side to luminal side.
Where is MAdCAM1 expressed?
Endothelial cells of high endothelial venules.
Once activated in mesenteric lymph nodes, T and B cells…
Enter bloodstream, return to effector sites.
EG: Lamina propria
T-cell homing receptors into Peyers patches
CCR 7, L-selectin
Where do mesenteric lymph nodes drain?
Thoracic duct.
Activated T-cell homing receptors for small intestine
CCR9, alpha-4 beta-7 integrin.
CCR9 ligand.
CCL25.
CCL25 location
Small intestine epithelium.
CCR10 ligand.
CCL28.
CCL28 location.
Epithelium of large intestine.
MAdCAM1 sites of expression.
Many mucosal sites.
TGF beta induces particular types of:
1) T cells
2) Antibodies
1) Treg, Th2
2) IgA.
Proteins associated with IgA dimers in mucosal tissue.
Secretory component.
J-chain.
Amount of IgA secreted per day.
3-5g.
pIgR location.
Basolateral face of intestinal epithelial cell.
IgA receptor on basolateral surface of epithelial cells.
pIgR.
pIgR
Polymeric IgA Receptor.
Origin of secretory component.
pIgR on epithelial cells. Part of pIgR cleaved off in the lumen, this forms the secretory component.
Functions of sIgA:
1)
2)
1) Blocks toxin attachment.
2) Blocks epithelial attachment.
Serves these functions in lumen, intracellularly and in lamina propria.
Properties of sIgA:
1)
2)
3)
1) Doesn’t activate complement cascade, to reduce inflammation.
2) Weak opsonin.
3) Long half life - secretory component protects against enzymatic degradation.
Respiratory tract inductive sites.
1)
2)
1) Adenoids.
2) Tonsils.
Secretions of alveolar epithelium.
Surfactant fluid.
NOT mucus.
Surfactant fluid properties.
Antimicrobial. SP-A, SP-B, SP-D.
Respiratory tract effector sites:
1)
2)
3)
1) Salivary glands.
2) Lacrimal glands.
3) Bronchus.
Ligands in small intestine for a-4 b-7 and CCR9 of activated T cells
a-4 b-7 - E-caderhin
CCR9 - CCL25
Ligands in large intestine for a-4 b-7 and CCR10 of activated t cells
a-4 b-7 - E-cadherin
CCR10 - CCL28
