Mucosal Immunity Flashcards
70-80% of all immunoglobulin producing cells in the body are located within what tissue, and what is the dominant Ig produced?
70-80% are located in the tissues of the mucosal immune system, and they primarily release IgA
Antigens that enter the digestive tract are taken up by what cells?
M cells
What do M cells do with antigen?
M cells internalize the antigen and transport it across the epithelium where antigen can be take up by APCs such as DCs.
What stimulates the formation of M cells?
M cells are formed in mucosal epithelium in response to signals from lymphocytes
How do DCs take up antigen from the GI lumen?
Antigen is captured from the lumen by DCs that extend across the epithelial layer.
What happens to antigen captured via DCs or M cells?
They are presented to lymphocytes located in specialized mucosal immune tissues, such as Peyer’s patches in the GALT
How to M cells take up antigen?
Endocytosis and phagocytosis
How is an immune response initiated after antigen is taken up by M cells in the gut?
Antigen is bound by DCs and presented to T cells which are then activated
Describe the Fc- mediated uptake of antigen in MALT tissue.
If there are already antibodies available to coat a bacterial pathogen, Fc receptors on the enterocytes of the gut can bind and take up the pathogen - it is transported to DCs
What happens to T cells that are activated in Peyer’s patches?
They migrate to the lamina propria of the small intestine
What does it mean that lymphocytes have tissue-specific homing receptors?
There are receptors/signals that attract lymphocytes specifically to the mucosa
Where are most of the MALT cells located with respect to the epithelial layer?
They are located just below the epithelial layer in the subepithelial layer (lamina propria), although there are some specialized areas that have intra-epithelial lymphocytes
Intraepithelial lymphocytes are what type of cell?
CD8+ T cells
Are peyer’s patches the initiator or effector sites? What does that mean?
Peyer’s patches are initiator sites- they are the site of antigen capture, but the response does not happen locally.
THe plasma cells all end up in the lamina propria (not the peyer’s patch)
How do the inductor cells get to the effector locations?
Following induction/antigen uptake, activated cells go into the lymphatic system, dump into the subclavian vein/into the blood stream, and are eventually honed to the effector sites of the mucosal tissue via tissue-specific homing receptors/molecules
In most cases, they go back to sites similar to where they were (i.e. gut usually goes to the gut, but occasionally they could go to the lung)
B cells in MALT selectively produce which antibody?
dimeric IgA
Which immune cells are particularly important in the gut?
T cells, specifically CTLs
Does mucosal immunity result in systemic immunity?
Yes- this is a big advantage of mucosal immunity
What is the job of intraepithelial lymphocytes?
To kill infected cells (virally infected cells) by perforin/granzyme and Fas-dependent pathways
WHat is the first line of mucosal defense? How is this accomplished?
Epithelial cells: they provide innate defense against most pathogens
The epithelial cells activate NFkappaB, which leads to the synthesis of pro-inflammatory cytokines which leads to destruction of the pathogens
Name two highlighted organisms that enter through the M cells and lead to infection of the mucosa
Shigella and Salmonella typhimurium
Salmonella enters through M cells and can kill them- requires a DC to take it up and start and immune process
Shigella: enters through M cells and infects other epithelial cells- requires activation of pro-inflammatory cytokines in order to defend and kill the pathogens
How could you be IgA deficient?
Genetic reason –> no switch region/ no IgA forms properly
How common in IgA deficiency?
1:500- 1:1000
What are the clinical problems seen with IgA deficiency?
1) Some people have no problems
2) Some people are at risk for increased mucosal infections
What is the difference between IgA1 and IgA2?
Different by the constant region of the heavy chain- they differ by a few amino acids -
Both found as dimers in the mucosa- they both have a secretory component characteristic of IgA
How does IgA exit the lamina propria and get into the lumen of the gut?
Poly-Ig receptors- they can bind dimeric IgA and pentameric IgM and endocytose the Ig and release it on the lumenal side - it takes part of the receptor with it, which is the secretory component!
Now the IgA is in the lumen and can protect against various pathogens.
Passive immunity is provided to babies through what class of antibody in breast milk?
secretory IgA
What are the advantages of mucosal immunization?
Easy to administer (orally)
Provides systemic and mucosal immunity
What are the problems with mucosal immunity?
1) short-lived: you don’t have lots of germinal centers to general plasma memory cells
2) It’s hard to generate a good immune reaction because of tolerance- ORAL TOLERANCE
Can systemic vaccinations provide mucosal immunity?
No- only mucosal vaccinations cause both mucosal and systemic immunity
What is required for the induction of mucosal immunitY?
Inflammation
