Mucosal Immunity Flashcards
mucosal tissues (MALT)
Gastrointestinal tract (GALT) Respiratory tract (BALT) Nasal mucosa (NALT) Salivary glands Lacrimal glands Mammary glands Genito-urinary tract
Main Ig
IgA
how much Ig is produced in mucosal areas
70-80%
M cells
specialized mucosal cells that take up antigens entering the digestive tract. They internalize and transport the antigen across the epithelium where it can be taken up by APCs
Peyer’s patches
lymphoid nodules located in the small intestine. site of T cell activation
B cells in MALT produce
IgA only
Intraepithelial lymphocytes
CD8 positive T cells that lie within the epithelial lining of the gut. Kill infected epithelial cells
process of IEL killing
- Virus infects mucosal epithelia cell
- Infected cell displays viral peptide via MHC class I to CD8 IEL
- Activated IEL kills infected epithelia’s cell by perforin/granzyme and Fas-dependent pathways
first line of mucosal defense
epithelial cell provide innate defense
3 ways salmonella typhimurium can penatrate the epithelium
- endter and kill M cells then infect macrophages and epithelial cells
- invade luminal surface of epithelial cells
- ender dendrites of DCs that are sampling the gut luminal contents
IgA deficiency
usually no clinical symptoms
IgA transport across the epithelium
binding of IgA to receptor on the basolateral face of epithelial cell
endocytosis
transport to apical face of epithelial cell
release of IgA dimer at apical face of epithelial
IgA function
Secreted IgA on the gut surface can bind and neutrilized pathogens (barrier function)
IgA is able to bind and neutralize antigens internalized in endosomes (intraepithelial viral neutralization)
IgA can export toxins and pathogens from the lamina propria while being secreted (excretory immunity)
IgA in breast milk
sIgA- provides passive immunity
The Potential of Oral (Mucosal) Immunization advantages and disadvantages
Advantages:
Ease of Administration
Generate both mucosal and
systemic immunity
Disadvantages:
Response may be short-lived
Difficult to elicit robust immune response-because of tolerance
Immunity
protective immunity for invasive bacteria, viruses, toxins, produces intestinal IgA Specific Ab present in serum t-cell response local and systemic effector and memory T-cells, enhanced response with reexposure
Tolerance
Antigens, food proteins, commensal bacteria, Ig produced is some local IgA, low or no Ab in serum, No local effector T-cell response, Low or no response to antigen reexposure
mouse experiment
mice fed with ovalbumin prior to injection did not develop immunity while those who were not fed did not
Commensal bacteria role
prevent toxins from getting a hold in the mucosa
largest organ of immune system
mucosa
most pathogens enter the immune system enter via
the mucosa
induction of immunity is mediated by
m cells
activated T and B cells home to
mucosal sites
Predominant Ig
mucosal (dimeric) IgA
tolerance vs immunity determined by
context of antigen presentation (DC); inflammation leads to immunity; no inflammation Treg cells
dimeric IgA is produced by
plasma cells within the mucosal lamina propria
pIgR
polymeric immunoglobulin receptor- binds to dimeric IgA on the basal surface of mucosal epithelial cells. the IgA-pIGR complex is endocytosed and transported through the cell to the luminal side. (only binds polymeric immunoglobulins (dimeric IgA or pentameric IgM)
secretory component
the part of pIgR that remains covalently bound to the dimeric IgA after a small piece is cleaved during transport.
cell types required for secretory IgA production
plasma cells (in lamina propria) and epithelial cells of the mucosa
pIgR deficiency
lack of IgA transport and increased mucosal leakiness
IgA functions at mucosal surfaces
barrier- binds bacteria and viruses and prevents adhesion and invasion into mucosal tissues
intraepithelial viral neutralization-IgA that is internalized by mucosal epithelial cells
excretory immunity-viral particles that complex with dimeric IgA in the lamina propria may be transported out by pIgR
passive immunity- sIgA in breast milk
key feature distinguishing between a response and tolerance
inflammation- antigen exposure+ inflammation= immune response. antigen exposure w/o inflammation= tolerance
tolerance initiation signal
DC does not get activated in the presence of TSLP, PGEx and TGF-B, Immature DC gives a weak co-stimulatory signal inducing Treg formation
Immunity initiation signal
microorganism penetrates the epithelium and activates DC, the DC expresses a strong co-stimulatory signal inducing T-cells to differentiate to Th1 and Th2 cells
where is dimeric IgA produced
by plasma cells within the mucosal lamia propria
