Lecture 13- Mucosal Immunology 2 Flashcards
Where are the mesenteric lymph node located?
These mesenteric lymph nodes are located at the base of the mesentry.
What is the function of these meseneteric lymph node?
- They collect lymph, cells and antigens from the intestinal mucosa
- main site for oral tolerance
What is oral tolerance?
-Avoidance of an immune response to foodstuff
How is oral tolerance induced?
Induce tolerance to allergens e.g. eat honey to treat bee venom allergy
What is mesentry?
- double fold of peritoneum that attaches the gut to the posterior abdominal wall
- has been considered an oragan
What does the mesenteric lymph node drain?
-Mesenteric lymph node from intestinal mucosa
What happens to food antigens?
Many food antigens will bypass lymphatic tissue and reach the liver through the portal vein
-immune cells in the liver sinuses have an important function in protecting us from microbes in the portal vein.
What is the main of passing blood through the liver sinuses?
The main program is tolerance production, in some instances, protective immune response need to be raised
Where are the intraepithelial lymphocyte located?
intra-epithelial cells are located in the basolateral part of the epithelium
Describe the inra-epithelial lymphocytes?
- Have an irregular shape
- have long extensions in close contact with neighbouring epithelial cells
- occur in variable numbers along the gut
What percentage of intra-epithelial are eosinophils?
12% of eosinophils in the intra-epithelial cells
What three groups are the intra-epithelial cell can be divided into?
1) TCRab+CD8ab+
2) TCRab+ CD8aa+
3) TCRab+CD4
Describe the pathway when a virus infects a epithelium cell?
IEL=intraepithelial lymphocyte
- Virus infects mucosal epithelium cell
- Infected cell displays viral peptide to CD8 IEL via MHC class I
- Activated IEL kills infected epithelial cell by perforin/granzymes and Fas dependent pathway
What happens to the infected epithelial cell?
- Epithelial cells undergo stress as a result of infection, damage or toxic peptides and express MIC-A and MIC-
- MIC-A and MIC-B are ligands for the NK cell activating receptor NKG2D which is also found on CD8aa+Tcells
- NKG2D on IEL binds MIC-A and B and activates the IEL. CD8aa homodimers also bind to TL
- Activated IEL kills the stressed cell via perforin/granzyme pathway
What is the T cell differentiation is influenced by?
epithelial cells and DC
what do the T reg cells produce and what is their function?
IL-10- required for maintaining food tolerance and class switch including TGF-beta and other mediators
What is the function of Th1 T cells?
Produce IFN-y and important in killing virally infected epithelial cells
What is the function of Th2 T cells?
Th2 T cells may be induced by worm infestation
-Produce IL-4 and IL-13 which increase fluid secretion, mucus secretions, bowel motility and smooth muscle contraction
What is the function of Th17 cells?
Th-17 cell produce IL17 and IL-22 which interact with tge receptors on the epithelial cells to regulate the production of mucins or defensins
what is the function of the dendritic cells?
- Sit in lamina propria
- Have long extensions reaching through the epithelium to sample the contents of intestinal tube
- present antigen to T cells
describe the journey of B cells?
Peyer’s patch –> mesenteric lymph node –> lymphatic stations –> thoracic duct –> venous blood –> lung –> arterial blood –> small arteries –> smallest arteries –> effector sites –> IgA secretion –> ?
How does the IgA get into the mucus?
The poly-Ig receptor at the basal surface of the epithelial cells can bind to the J chain of the IgA and to lesser extent IgM
- allows the trans-endothelial of IgA /IgM
- this mechanism helps enriching these immunoglobulins in the mucus where they exert their function
Explain the fucntion mucosal IgA?
- IgA is the main mucosal antibody in the secretions
- IgA against food antigens provides immune exclusion
- IgA activates the complement system weakly
- Secretions of the IgA (coupled to J chains) depends on the trans-cellular transport mechanism
what does the gut homing of B-cells and T cells depend on?
-Depends on retinoic acid derived from dietary vitamin A
Describe the process of conversion of vitamin A to retinoic acid by the dendritic cells(DC)?
DC in the gut associated tissue (including Peyers patch and mesenteric lymph nodes) are induced by thymic stromal lymphopoietin (TSLP) and other factors to express:
Retinaldehyde dehydrogenase
-This enzyme converts dietary vitamin A to retonoic acid
What happens to activated B cells or T cells that are exposed to retonoic acid?
-Induces expression of the chemokine receptor CCR9 and the integrin a4b7 on the plasma cells and the effector T cells
what happens to the effector T cells once the chemokine receptor is induced?
The effector T cells enter the circulation and home back into the gut lamina propria
Why does the effector T cells home back to the lamina propria?
- Imprinting of CCR9 and a4b7 receptors on the lymphocytes in the inductive sites
- The CCL25 (ligand for the CCR9) and the adhesion molecule MadCAM (ligand for a4b7) are displayed on the lamina propria venular endothelial cells
Explain what drives the homing process for the effector cells?
- Different combinations of homing receptors will guide effector cells to the different tissues
- Tissue sites upregulation of the respective ligand molecules will be related to the situation in these tissues
what is the effect of the Vitamin A deficiency?
–reduced oral tolerance due to reduced homing of regulatory T cells
