Mucosal immunity

Question 1

What makes up MALT

Answer 1

GI tract
Respiratory tract
Urogenital tract
Exocrine glands

Question 2

What allows for the unique balance of the mucosal layer

Answer 2

thin permeable layer that is easily breached with commensal microorganisms

Question 3

What are the three lymphoid tissue?

Answer 3

Lamina Propria
Peyer’s Patches with M cells
Isolated lymphoid follicles - no afferent lymphatics

Question 4

How is GALT adaptive immune response different from the AI in the periphery?

Answer 4

response can be initiated locally in the GALT

Question 5

Which intestinal lyphocytes are loose? embedded?

Answer 5

Lamina propria lymphocyte - loose

Intraepithelial lymphocyte - embedded

Question 6

Which lymphoid tissue is a dome with M cells

Answer 6

Peyer’s patch

Question 7

How does the AI sys become active?

Answer 7

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

Question 8

What are distinct features of mucosal immune system?

Answer 8

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

Question 9

What are the specialized lymphoid cells

Answer 9

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

Question 10

The lymphocytes in gut immunity are

Answer 10

activated effectors

Question 11

What cell is rarely found in the healthy gut?

Answer 11

neutrophil

Question 12

Why is there very little inflammation in the gut?

Answer 12

DC and Macs lack:

TLRs
Proinflammatory signaling receptors

Question 13

What is Gut tolerance?

Answer 13

Restrain, but not remove microorganisms

Question 14

Where is restricted recirculation of naive B cells and T cells seen?

Answer 14

the gut

Question 15

What is required to go from LNs/Spleen –> Peyer’s patches/MLNs via HEVs?

Answer 15

CC21 and CCL19

CCR7

Question 16

If Ag encountered, what is lost and gained to be mucosally targeted?

Answer 16

CCR7 lost

L-selectin gained - keeps it inside mucosa

Question 17

What interaction is needed for recirculation of cells back to site of activation?

Answer 17

a4b7 (on effector T cells) and MAdCAM-1 (on endothelium)

Question 18

What is secreted by gut epithelium to guide naiive lymphocytes from LN/speen into the mucosa? Whats found on the lymphocyte?

Answer 18

CCL25 - secreted

CCR9 - on lymphocyte

Question 19

What allows IELs to be sandwiched between epithelial cells?

Answer 19

aEb7 - expressed

interacts with E-cadherin

Question 20

What are the special homing receptors under the control of? what are they mediated by?

Answer 20

Intestinal DC

mediated by retinoic acid (Vit A)

Question 21

What are B cells controlled by to make IgA?

Answer 21

TGF-beta

Question 22

What are the homing receptors that direct T cells into Peyer’s patches from blood vessels?

Answer 22

CCR7 and L-selectin

Question 23

What is needed to home Activated T cells to the lamina propria and intestinal epithelium of small intestine?

Answer 23

a4b7 and CCR9

Question 24

What form of IgA predominates in the gut?

Answer 24

Dimeric form

Question 25

Why does IgA cause little inflammation?

Answer 25

No complement activation

doesn’t act as a opsonin

Question 26

IgA1 is (long/short). ____ flexible and _____ to cleavage.

Answer 26

long
more
susceptible

Question 27

IgA2 is (long/short). ____ flexible and _____ to cleavage

Answer 27

shorter
less
resistant

Question 28

How does IgA get released from Lamina propria to the lumen?

Answer 28

1. IgA-secreting cell – IgA released with J chain
2. binds Poly-Ig receptor on the basolateral surface of the epithelial cell
3. endocytosis
4. transcytosis to apical face
5. release of IgA dimer + secretory component

Question 29

What makes IgA an excellent toxin eliminator in the gut?

Answer 29

• secreted IgA binds and neutralize pathogens and toxins
• IgA bind and neutralize Ag internalized in endosome
• IgA export toxins from LP while being secreted

Question 30

What are the Ag for oral tolerance?

Answer 30

food proteins, commensal bacteria

Question 31

Ig production in oral tolerance? T-cell response?

Answer 31

local IgA, low/no Ab in serum

no local effector T-cell response (still lots of activated cells)

Question 32

What is the response to Ag reexposure in oral tolerance? Why?

Answer 32

Low or no response because no inflammation

Question 33

How does Abx affect gut epithelia?

Answer 33

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

Question 34

Mucosal vaccination: Intranasal routes

Answer 34

NALT – BALT – Reproductive areas - cervical/vaginal

Influenza vaccine

Question 35

Mucosal vaccination: Oral routes

Answer 35

Mouth –> esoph –> stomach –> colon –> intestine –> Mammary glands

Rota virus