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24 Cards in this Set
- Front
- Back
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What cell-types make up the intestinal epithelial barrier?
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-enterocytes [majority] (have BB)
-M cells (no BB, rather microfolds) -GALT underlies epithelium |
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How is GALT functionally and histologically divided?
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-inductor sites
-effector sites |
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What role in immunity does the intestinal epithelium play?
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-dual role of controlling access of Ag's and pathogens & absorbing dietary nutrients
-aided by tight jnxns -aided by BB glycocalyx - relatively impermeable to macromolecules and bacteria, but permeable to digested nutrients -aided by sp. adaptations: i. Defensins - anti-microbial peptides ii. IgA iii. mucins iv. trefoil peptides (secretory proteins in GI tract; may protect mucosa; stabilize mucous layer, etc.) |
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What is the effector site of GALT?
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-Peyer's patches (contain M cells)
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What is the inductive site?
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-Lamina propria (more loosely organized than PP's)
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What are the 5 major compartments of intestinal lymphoid tissues?
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1.Peyer's patches
2.Intraepithelial lymphocytes 3.Lamina propria 4.Mesenteric lymph nodes 5.(Cryptopatches) |
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Describe Peyer's Patches.
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-lymphoid aggregates in sm. intestine
-extend through the mucosa -important source of T and B cells -have M (microfold) cells for Ag recognition/processing |
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Which lymphoid cells are present in the lamina propria?
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-B, T, m0's, mast cells, eosinophils
-80% of B cells produce IgA -CD8+ cells along epithelium -majority of T-cells are CD4+ |
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Which cells are capable of transporting antigen across the epithelial border?
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1.M cells:
- deliver Ag to Ag-presenting cells (APC) in Peyer's patch 2. Dendritic cells (type of APC): -extends its processes THROUGH tight jnxns to sample Ag DIRECTLY while maintaining integrity of barrier! (how cool!) |
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How do B-cells become IgA secreting plasma cells?
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-mucosal B cells undergo class switch recombination under influence of TGF-beta
-IgA committed B cells move from Peyer's patches to lamina propria -under the influence of IL-5/IL-6, they become IgA plasma cells -IgA binds to poly IG receptor on BASOLATERAL surface of enterocytes -binding to R causes it to be transported to APICAL surface where it is secreted |
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What is the function of IgA in GI immunity?
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1. guards epithelium from microbial entry
2. acts as "sump-pump": excretes bound Ag's that penetrate barrier back into lumen |
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What is a Th1-mediated response?
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-Th0 cells become Th1 cells due to secretion of IL-12 by m0's
-Th1 cells produce IFN-gamma. -leads to a CELL-MEDIATED immune response (ie. granulomatous) |
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What is a Th2-mediated response?
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-Th0 cells become Th2 cells that produce IL-4, IL-5 & IL-13.
-leads to a HUMORAL immune response (ie. these cytokines contol B-cell differentiation into Ig-secreting plasma cells)[IgA in the GI tract] |
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Is ulcerative colitis Th1 or Th2 mediated?
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-Th2
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Is Crohn's Th1 or Th2 mediated?
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-Th1
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What are cryptopatches?
(Cryptopatches: intestinal sites for γδ T-cell replication; Gastroenterology 1998; 114:1121-1122) |
-tiny mucosal lymphoid aggregates scattered throughout the small and large intestine that act as local sites for production and maturation of γδ and αβ T lymphocytes, independent of the thymus gland. Cryptopatches are separate from Peyer's patches and contain different lymphocyte populations.
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What are intra-epithelial lymphocytes?
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-sub-population of T cells residing b/w epithelial cells, above the BM
-1/3 of IELs are γδ T-cells that dvlp in cryptopatches -enterocytes produce IL-7 which is important for dvlpmnt of IEL's |
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What is the role of CD8+ and CD4+ T-cells in the lamina propria?
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-they are memory cells belonging to "effector memory" subset
-these memory T-cells are different from central memory T-cells found in lymphoid organs -able to respond to Ag's faster than central memory T-cells |
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Why don't commensal bacterial activate the GI immune system?
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-for the most part, they can't enter Peyer's patches b/c they are trapped in mucous layer
-seems that DC's carrying non-invasive bacteria remain in the lamina propria and don't go to Peyer's patches -possibly there are different signalling pathways by Toll-like Receptors for pathogenic and non-pathogenic bacteria |
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What is the role of enterocytes in activating the innate immune system?
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-have Toll-like Receptors which if bind with PAMPS (pathogen associated molecular protein) may lead to direct cytokine signaling (vs. indirectly via activation of TLRs on professional APCs in Peyer's patches and lamina propria)
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What is the role of enterocytes in activating the adaptive immune system?
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-enterocytes secrete m0 inflammatory protein which recruits immature DC's to Peyer's Patch to take up Ag
-there is an impaired humoral response in mice lacking necessary parts of this pathway |
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What is NOD2?
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-gene on chromosome 16
-NOD2 protein expressed only in monocytes -regulates apoptosis -NOD2 mutations occur in 10-15% of pt's w/ Crohn's -leads to alteration in cell signalling producing chronic inflammation |
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What is oral tolerance?
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-food is a source of Ag stimulation
-therefore must have non-responsiveness to food to prevent hypersensitivity rxns - =oral tolerance |
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What is the MOA of corticosteroids in IBD?
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- inhibit NF-kappa B (same signalling pathway that is altered w/ NOD-2 mutations)
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