Mucosal Immunity - Bowden Flashcards
What is the primary function of mucosal immunity? 3
Provide defense at all mucosal surfaces (GI, respiratory, and urogenital)
What is the secondary function of the mucosal immunity? 3
Prevents Ags from entering circulation
Prevent an entire systemic immune response to an inappropriate Ag exposure
What’s the major difference between mucosal and systemic immunity? 4
Mucosal immunity focuses on tolerance (stop it from getting in)
Systemic immunity is active against pathogens (its here and needs to leave)
How do we maintain oral tolerance? 5
By eating food (aka Ags)
Low [food]:
Th2 induction (IL-4 & IL-10), TGFβ secretion
=active suppression
High [food]:
Deletion or synergy of Th1 and Th2 cells
= clonal anergy and depletion
What is the stratification portion of immune regulation? 6
Minimizes contact between bacteria and epithelial surface via:
Mucin
Anti-bacterial proteins
IgA
What is the compartmentalizations portion of immune regulation? 6
Add
7
Add
What is immune exclusion? 8
Secreted IgA binds Ag (macromolecular pathogens) and keeps them trapped in the mucus until they degrade
What is the role of goblet cells
Innate immunity
Secrete mucus to serve as an anti-bacterial barrier
What is the role of Paneth cells? 10
Innate immunity
Secretes antibacterial cells
What is the role of M cells? 10
Innate immunity
Allow for sampling of Ag
What are the cellular components of the mucosal barrier in the Gut? 11
Enterocytes - held together by tight junctions
Normal flora
13
Add
Why does IgA represent as a dimer held together by a J chain within an enterocyte, but as a monomer in circulation? 14
There is a secretory component on the J chain of IgA dimers that allows it to be secreted into the lumen of the GI tract
Which adaptive cell type do commensal bacteria not activate? What is the consequence of this? 15
Commensals do not activate Th1 which ensures there will be no inflammation
What is the function of M cells? 16
Microfold (M) cells
Allows for a sampling of WHOLE cells, like HLA, but without any cleaving
What is the cluster differentiation for DCs specific to GALT? 17
CD103+
19
Add
What do GALT DCs produce? 17
Retinoic Acid (RA)
TGF-β + IL-2 + IL-10 –> antiinflammatory
What kind of B cell population is present within GALT? 20
B-1 cell population
Either mIgA B cells or IgA plasma cells
What are some very important characteristics of IgA? 21
Doesn’t fix complement or cause an inflammatory response
Instead simply neutralizes
This makes sure we don’t have a ton of inflammation in our gut
What are the Intraepithelial lymphocytes? 23
CD8+
Tregs (~10%)
CD4+ (δ/γ)
How do γ/δ T cells differ from α/β T cells? 24
γ/δ exist mucosal compartments
Recognize lipid Ags
Not HLA restricted - instead directly activated by PAMPs and DAMPs
What is the role of Th17 in the gut? 25
Protect against EC bacteria and fungi
Regulated by DCs and Tregs (stop inflammation)
What is the regulatory DC? 26
CD103+ (produce RA and TGF-β)
Produces tolerance
What is selective IgA Deficiency? 29
Most common primary Ab deficiency
Presents as recurrent sinus infections (IgA responsible for protecting sinus)
Why is IgA deficiency almost never diagnosed? 29
IgM also contains a J chain and is able to be secreted across mucosal surfaces
What diseases are related to inappropriate mucosal immune response? 30
IBD (crohns, ulcerative colitis)
Food allergies
Celiac Disease (gluten sensitivity)
What happens to the GI in malnutrition and starvation? 32
Mucosal atrophy and increase in intestinal permeability
Decrease IL-4 and IL-10
Decrease sIgA
CD4:CD8 ratio 1:1
33
Read
