Mucosal Immunity Flashcards
What are specific challenges of the GI Tract immune system?
Tolerance to food antigens
Tolerance to microbiota but responsive to pathogens
Enormous surface areas
What are specific anatomic structures of the GI tract’s immune system?
Tonsils
Peyer’s Patches
LP Follicles
What are M cells?
What do they do?
Where are they located?
Specialized cells that have epithelium which target bacteria for adhesion
Transports the bacteria to DCs
Follicle Associated Epithelium (FAE) in the Peyer’s Patches
What is special about the histology of the Peyer’s patch?
All lymphocytes, physiologically inflammed
What causes a tolerogenic DC?
What are the roles of tolerogenic DCs?
Retinoic acid, TSLP, TGFb causes a tolerogenic DC
Results in production of tolerogenic T-cell
Th17 and regulatory T-cells
Also they induce production of MadCAM, CCL25, and CCR9 for mucosal trafficking
What are the 3 compounds responsible for mucosal trafficking and which cell type is each associated with?
CCR9 – Immune cells
CCL25 – Epithelium
MadCAM – Endothelium
What are the two mechanisms of B cell class switching in the gut? Describe each.
T-dependent
DCs in Peyer’s patch present Ag and activate naïve T cells to Th1
CD40L on Th1 cells and TGFb from DCs activate naïve B cells
Becomes a differentiated plasma cell which secretes IgA
T-independent
TLRs on DC stimulate release of TGFb, APRIL, BAFF with IL6 and Retinoic Acid These induce class switching of B cells
What kinda of plasma cells predominate in the gut?
What does it secrete?
What is the relative abundance of the Ig in the blood?
IgA secreting plasma cells in LP
2-4 grams IgA/day
Only 25% of total Ig in blood
What are the molecules involved for T cell recognition?
What are the molecules involved for B cell recognition?
Recognition by T Cells
TCR – 1st signal recognize peptide antigen; CD4 and CD8 is recognition component
Co-stimulatory molecule – 2nd signal recognize co-stimulatory receptor on APC
Recognition by B cells
BCR – 1st signal is by membrane bound IgM
Costimulatory molecule – 2nd signal is complement protein or TLR
What are the secreting steps for IgA?
Dimeric IgA bound at J-chain is released into LP
J-chain binds to poly-Ig receptor to enter mucosal epithelial cell
Complex is cleaved to enter lumen
What are the 3 classes of substances which induce an immune respone?
- *Immunogen** – Molecule that induces an immune response
- *Antigen** – Molecules that bind to Ab to TCR
- *Tolerogen** – Molecule that induces immune unresponsiveness to subsequent doses of the molecule
What is the concept of immunologic tolerance?
Typically suppression of immune response due to self antigen
What factors determine immunogencicity?
Size – Large increases
Dose – Intermediate increases (High or low does not)
Route of Entry – SubQ > Intraperitoneal > IV > Intragastric
Composition – Complex increases
Adjuvant – Bacteria increases
Interaction with MHC complex – Complex increases
How is mucosal tolerance mediated?
IgA – Neutralizes complex antigens from generating a full response
Th17 – Strengthens gut mucosa
T-reg – Mediates non-responsiveness
What are the general causes of autoimmunity?
Genetic susceptibility
Environmental trigger
Uncontrolled immune response
