Term
| Two major challenges to the mucosal immune system? |
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Definition
1) distinguish between foreign antigen and pathologenic organisms
2) do this in the context of commensal bacteria |
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Term
| What histological layer are IgA producing cells located in? |
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Definition
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Term
| Where are CD8+ cells located in the mucosa? |
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Definition
| - in the mucosal epithelium |
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Term
| Two pathways for lymphoid induction process in the mucosa |
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Definition
1) antigen taken up by M-cells and transported through cytosol across the epithelium, then uptake of antigen on basolateral side of M-cell by APC.
2) Dendritic cell takes up antigen by extending through the epithelial tight junction into the lumen. |
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Term
| What follows up take by dendritic cell/APC in mucosa? |
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Definition
| - APC takes antigen to peyer's patch (in the intestine) and presents to lymphocytes |
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Term
| After presentation of antigen in the peyer's patch, what do lymphocytes do? |
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Definition
- migrate from mucosal site and travel through mesenteric lymph nodes, then into the lymph
- via the thoracic duct, they exit the lymph and enter the circulation |
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Term
what do the mucosally activated circulating lymphocytes do?
What do they express and where do they go |
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Definition
-retrun to the gut
- activated T-cells express α4:β7 integrin and CCr9 travel to lamina propria and epithelium
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Term
What do gut homing T-cells bind to exit circulationa and arrive in gut?
What do they bind in epithelium?
|
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Definition
-bind MAdCAM1 on endothelium with α4:β7 and L-selectin
-Bind CCL28 with CCR9 and CCR10 |
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Term
Where does antibody production result after administration of antigen at one mucosal site?
-give an example |
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Definition
- antibody production can occur at other mucosal sites, however there is preference
(e.g. antigen introduced to NALT is more likely to lead to more robust response in respiratory sites than GI sites) |
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Term
What do B-cells switch to in the mucosa?
What induces this? |
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Definition
- isotype switch to dimeric IgA
- mediated by T-cells in the inductive sites |
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Term
What is generally the result systemically of an immune response at a mucosal site?
What does this imply? |
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Definition
- typically a systemic response occurs such that antibodies can be detected in the serum.
- A mucosal encounter gerneates subsets of T and B cells that home to mucosal sites as well as spleen and regional nodes |
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Term
| What is likely function of gut epithelial CD8 CTLs? |
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Definition
| - probably kill virally infected cells via presentation of viral particles through MHC I |
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Term
What is the most common primary immune deficiency?
Two different types? |
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Definition
- IgA deficiency
- complete abscence of IgA or decreased but detectable levels of IgA |
|
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Term
| Four reasons to suspect IgA deficiency |
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Definition
1) Family history of IgA deficiency of agammaglobulinanemia
2) High incidence of oral infections
3) Frequent respiratory infections
4) Chronic diarrhea |
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Term
| Autoimmune diseases associated with IgA deficiency |
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Definition
1) SLE
2) juvenile rheumatoid arthritis
3) Thyroiditis |
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Term
| Why not give IgA to a person with IgA deficiency? |
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Definition
| - their immune system may make anti-IgA in response to IgA treatment. |
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Term
| Comparison of serum vs. secreted IgA (monomer/dimer/trimer etc, and what percentage of the Ig in the area is it?) |
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Definition
serum: monomeric, makes up 12% of Ig
mucosl sites: dimeric, makes up 96% of Ig |
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Term
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Definition
1) created by plasma cells in mucosal lamina propria
2) Binds to polymeric immunoglobin receptor on the basal surface of mucosal epithelial cells
3) The IgA pIGR complex is endocytosed and transported through the epithelial cell to the lumenal surface for realease, during which a small fragment of pIGR is cleaved and lost
4) The remaining fragment of pIGR remains as secretory component and is covalently bound to dimeric IgA |
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Term
| What are two effects of pIGR genetic deficiency in mice? |
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Definition
- decrease in IgA transported
- mucosal leakiness |
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Term
| Three ways/places IgA can act in mucosal area |
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Definition
1) secreted IgA on the gut surface can bind and neutralize pathogens and toxins
2) IgA is able to bind and neutralize antigens internalized in endosomes
3) IgA can export toxins and paothogens from the lamina propria while being secreted. |
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Term
| How does IgA function as a barrier to infection in its secreted form? (i.e. in GI lumen) |
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Definition
| - can bind to bacteria and viruses and prevent their adherence and invasion into mucosal tissues. |
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Term
| How does excretory immunity provided by IgA work? |
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Definition
| - IgA may bind viral particles in the lamina propria, then be endocytosed via pIgR and transported out into lumen. |
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Term
| What is the chief example of passive immunity of IgA? |
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Definition
| - sIgA in breast milk provides passive immunity to the infant |
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Term
Advantages of oral immunization
Disadvantages of oral immunization
Two examples |
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Definition
Advantages: ease of adminsitration, generates both mucosal and systemic immunity
Disadvantage: difficulty in eliciting robust respone, may not be long lasting
- polio vaccine
-nasal spray for influenza |
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Term
Difference between antigens that cause an immune response and those that do not?
in the intestine, what is tolerence believed to mediated by? |
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Definition
- antigens that cause an immune response generally cause inflammation as well.
- mucosal dendritic cells |
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Term
How is it believed that dendritic cells induce tolerence of commensal bacteria?
How is this different than in the absence of commensal bacteria? |
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Definition
- in presence of commensal bacteria, production of TGF-β, TLSP and PGE inhibit cell maturation
- the DC in the mesenteric lymph node gives weak co-stimulatory signals and induce CD4's to become Tregs
- invasive bacteria penetrate epithelium, activate DC
- In lymph node, the activated DC gives strong co-stimulatory signal, induce CD4's to become Th1 or Th2 |
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Term
| What is the result of an immune response to commensal bacteria? |
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Definition
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