Flashcards in L18: Mucosal Immunity Deck (30):
Antigens entering the digestive tract are taken up by specialized mucosal cells called
B cells in the mucosa are selectively induced to produce
dimeric IgA rather than other isotypes.
Induction of a response via a mucosal site generally also elicits a
systemic immune response, such that serum antibodies can be detected. This indicates that a mucosal encounter with antigen generates subsets of T and B cells that home to mucosal sites and also to spleen and regional nodes.
What are IELs?
A distinct population of lymphocytes, mostly CD8+ T cells are found in the gut epithelium. The function of these cells is still not clear but they may readily kill infected epithelial cells.
In a mucosal response to infection, local inflammatory cells are activated via
What's the most common primary immune deficiency?
Selective IgA deficiency is the most common primary immune deficiency, with an estimated incidence of 1 per every 500 to 1000 persons. The precise characteristics of the deficiency are variable, as some patients have complete IgA deficiency but others have decreased but detectable levels of IgA.
Reasons to suspect selective IgA deficiency include
1) a family history of IgA deficiency of agammaglobulinemia,
2) a high incidence of oral infections,
3) frequent respiratory infections, and
4) chronic diarrhea.
Autoimmune diseases, including SLE, juvenile rheumatoid arthritis, and thyroiditis, are often associated with
selective IgA deficiency.
Immunoglobulin therapy is generally not indicated, for IgA deficiency. Why?
The patient’s normal antibody response can produce anti-IgA antibody in response to IgA treatment. People with a complete absence of IgA may develop allergies or even anaphylactic shock if given gammaglobulin.
The predominant immunoglobulin in mucosal secretions is
Serum Ig. What % is IgA? What form is the IgA?
12% IgA class, primarily monomeric.
Secreted Ig at mucosal sites – what % is IgA? What form is the IgA?
96% IgA, primarily dimeric IgA in mucous secretions (called secretory IgA, or sIgA)
The production of secretory IgA (sIgA) requires what cells?
Plasma cells in the lamina propria and epithelial cells of the mucosa.
70-80% of all Ig producing cells, are where?
Mucosal areas! Most of these cells make IgA!
What's the polymeric immunoglobulin receptor (pIGR)?
Located on basolateral surface of mucosal epithelial cells. Helps endocytose the IgA, in prep for secretion
Where does the IgA get it's secretory component from?
the cleaved pIGR!
Deficiency in pIGR?
Mice that are genetically deficient for pIgR exhibit the expected decreases in IgA transport.
PIgR deficiency also leads to an increased mucosal leakiness.
Barrier function of IgA?
Secretory IgA can bind to bacteria and viruses and prevent their adherence and invasion into mucosal tissues. Secretory IgA can neutralize many viruses in this way, including polio, herpesvirus, coxsackie virus, and rotaviruses. Secretory IgA can also neutralize bacterial toxins at mucosal surfaces
What can IgA do to an intracellular virus?
IgA that is internalized by mucosal epithelial cells (via the pIgR) may contribute to intracellular viral inactivation.
What if the virus penetrates past the epithelium, into the lamina propria?
Viral particles that complex with dimeric IgA in the lamina propria may be endocytosed and transported out by the pIgR pathway.
Passive IgA immunity. 1st thought?
sIgA in breast milk provides passive immunity to the infant.
Name 3 pathogens that enter through mucosal surfaces
cholera, HIV, influenza
2 advantages of mucosal immunization?
1. Ease of administration (oral)
2. Generates BOTH mucosal and systemic immunity!!! BIG IDEA!
2 disadvantages of mucosal immunization?
1. Difficulty in eliciting robust response
2. Response may not be long-lasting
Give me an example of a successful oral vaccine
An example of an effective oral immunization is the polio vaccine. Effective nasal spray vaccines for influenza have recently been developed.
BONUS: What are some strategies for boosting uptake of foreign antigen at mucosal induction sites?
New strategies for oral immunization include the use of cholera toxin chimeric molecules as well as recombinant avirulent bacteria (e.g. avirulent salmonella expressing S. pneumoniae proteins).
Can also target M cells using bacteria and viruses that preferentially bind M cells or antigen encased in biodegradable particles such as latex.
How does the mucosa differentially mount an immunogenic response, versus tolerance?
The key feature that appears to distinguish between the induction of a response and the induction of tolerance is INFLAMMATION.
Antigen encounters that occur alongside inflammation generally illicit an immune response. Antigen encounterd in the absence of inflammation generally induces tolerance.
Peptides generally induce tolerance, unless
attached to a mucosal adjuvant, such as cholera toxin.
Why do mucosal DC's turn a blind eye to commensal bacteria? Be specific.
TSLP, PGE2, and TGF-B from commensals suppress DC maturation.