Mucosal immunity Flashcards
What makes up MALT
GI tract
Respiratory tract
Urogenital tract
Exocrine glands
What allows for the unique balance of the mucosal layer
thin permeable layer that is easily breached with commensal microorganisms
What are the three lymphoid tissue?
Lamina Propria
Peyer’s Patches with M cells
Isolated lymphoid follicles - no afferent lymphatics
How is GALT adaptive immune response different from the AI in the periphery?
response can be initiated locally in the GALT
Which intestinal lyphocytes are loose? embedded?
Lamina propria lymphocyte - loose
Intraepithelial lymphocyte - embedded
Which lymphoid tissue is a dome with M cells
Peyer’s patch
How does the AI sys become active?
Naiive T cells – enter via HEV – contact DC – Ag presentation – activated – leave via efferent lymphatics to mesenteric lymph nodes – blood circulation – back to gut lymph and enter inflamed/damaged/infected area of gut
What are distinct features of mucosal immune system?
Overall: active effectors and suppressors
1 Intimate intrxn between mucosal epithelia and lymphoid tissue
2 Discrete compartments/organized structures
3 Specialized Ag-uptake mechanisms
4 Activated/mem T cells predominate even in absence of infection
5 nonspecifically activated ‘natural’ effector/regulatory T cells present
6 active downregulation of response
7 Inhibitory macs and tolerance-inducing DC
What are the specialized lymphoid cells
M cells - Ag transport from apical to basolateral
DC - embedded in epithelia - extend process to capture Ag from lumen
Intraepithelial lymphocyte (IELs) - CD8+ a/b or g/d mostly effectors
The lymphocytes in gut immunity are
activated effectors
What cell is rarely found in the healthy gut?
neutrophil
Why is there very little inflammation in the gut?
DC and Macs lack:
TLRs
Proinflammatory signaling receptors
What is Gut tolerance?
Restrain, but not remove microorganisms
Where is restricted recirculation of naive B cells and T cells seen?
the gut
What is required to go from LNs/Spleen –> Peyer’s patches/MLNs via HEVs?
CC21 and CCL19
CCR7
If Ag encountered, what is lost and gained to be mucosally targeted?
CCR7 lost
L-selectin gained - keeps it inside mucosa
What interaction is needed for recirculation of cells back to site of activation?
a4b7 (on effector T cells) and MAdCAM-1 (on endothelium)
What is secreted by gut epithelium to guide naiive lymphocytes from LN/speen into the mucosa? Whats found on the lymphocyte?
CCL25 - secreted
CCR9 - on lymphocyte
What allows IELs to be sandwiched between epithelial cells?
aEb7 - expressed
interacts with E-cadherin
What are the special homing receptors under the control of? what are they mediated by?
Intestinal DC
mediated by retinoic acid (Vit A)
What are B cells controlled by to make IgA?
TGF-beta
What are the homing receptors that direct T cells into Peyer’s patches from blood vessels?
CCR7 and L-selectin
What is needed to home Activated T cells to the lamina propria and intestinal epithelium of small intestine?
a4b7 and CCR9
What form of IgA predominates in the gut?
Dimeric form
Why does IgA cause little inflammation?
No complement activation
doesn’t act as a opsonin
IgA1 is (long/short). ____ flexible and _____ to cleavage.
long
more
susceptible
IgA2 is (long/short). ____ flexible and _____ to cleavage
shorter
less
resistant
How does IgA get released from Lamina propria to the lumen?
- IgA-secreting cell – IgA released with J chain
- binds Poly-Ig receptor on the basolateral surface of the epithelial cell
- endocytosis
- transcytosis to apical face
- release of IgA dimer + secretory component
What makes IgA an excellent toxin eliminator in the gut?
- secreted IgA binds and neutralize pathogens and toxins
- IgA bind and neutralize Ag internalized in endosome
- IgA export toxins from LP while being secreted
What are the Ag for oral tolerance?
food proteins, commensal bacteria
Ig production in oral tolerance? T-cell response?
local IgA, low/no Ab in serum
no local effector T-cell response (still lots of activated cells)
What is the response to Ag reexposure in oral tolerance? Why?
Low or no response because no inflammation
How does Abx affect gut epithelia?
kills commensal bacteria colonized on the colon, allows bacteria to gain foothold and produce toxins that cause mucosal injury
–> neutrophils and red blood cells can now leak into gut between injured epithelial cells
Mucosal vaccination: Intranasal routes
NALT – BALT – Reproductive areas - cervical/vaginal
Influenza vaccine
Mucosal vaccination: Oral routes
Mouth –> esoph –> stomach –> colon –> intestine –> Mammary glands
Rota virus
