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Flashcards in L13 Deck (43)
1

What are the 2 main ways antigens can be transported by cells across mucosal epithelium?

M cells
Trans-epithelial DCs

2

When lymphocytes are primed in MALT, what effector sites are they attempting to return to? How?

Effector sites = lamina propria & IEL
How:
- Retinoic acid-dependent expression of a4b7

3

What are the 2 main division of mucosal associated lymphoid tissue (MALT)? Name subtypes of each.

1. Inductive site
BALT = bronchus
GALT = gut
NALT = nasopharinx
2. Effector site = lymphocytes @ epithelium & lamina propria

4

How do cells move from the induction --> effector site?

Break/transport across epithelium
B/G/NALT
Lymph
Local lymph nodes
Thoracic duct
Blood
Back to respective epithelium/LP

5

Describe the 2 types of inductive sites found in the GALT.

1. ILF = isolated lymphoid follicle
- No distinct T/B zones in germinal centers--> mostly B cells
- THROUGHOUT GI tract
2. Peyer's patch

6

Describe the characteristics of follicle associated epithelium.

ONLY above lymphoid tissues (Peyer's patches)
NO goblet cells (little mucous)
YES M cells - for passage to lymph tissue

7

Since the lamina propria is the major effector site, what cell type dominates here?

B cells!

8

What are the 2 layer of mucous produced by goblet cells?

Outer layer - contains microbes
Inner layer - sterile with antimicrobials (defensins) & Abs

9

What junctions hold together epithelial cells?

Tight jxns

10

What other product, aside from mucous, is produced by goblet cells?

TFF 3 - into mucous, promotes migration of cells and epithelial healing

11

What are paneth cells? Where do you find them?

@ bottom of intestinal crypts
Make defensins

12

What are intestinal epithelial stem cells? Where do you find them?

@ bottom of intestinal crypts
Constant replenishment of epithelial cells --> upward migration

13

What surface receptors do epithelial cells express?

TLR
MHC 1 & 2

14

What is the fxn of M cells? What receptors do they express?

Transport antigens from lumen --> dendritic cells
No microvilli or lysosomes - no digestions of phagocytosed particles
Express:
- TLR2 & TLR4 - PAMP uptake (non-specific)
- IgA receptors - specific uptake

15

What are receptors commonly expressed by DCs & macrophages in the intestinal epithelium?

CX3CR1
CD103 - promotes gut specific development of T & Treg cells
CD11b/c

16

When stimulated/bound to antigen, what do DC produce?

IFN gamma
TNF
NET: helps Th1, increased leakage across epithelium

17

Which 3 T cell types do DC stimulate the differentiation of when bound to antigen? What do each product? What is the function of each?

1. Th1 - IFN gamma & TNF - increased leakage, macrophage inflammation
2. Th2 - IL13 - recruit eosinophils, promote IgE from B cells
3. Treg - IL10 & TGFbeta - aTENuate the infam response of Th1s

18

What cytokines do epithelial cells secrete to increase Treg maturation?

TGF beta
Retinoic acid

19

Explain the function of retinoic acid.

Vitamin A breakdown product
Induces tolerance
- Increases Treg when you're having Th1 response to something that is relatively non-pathogenic

20

What are 4 main characteristics of Peyer's patches?

1. Germinal centers with distinct T/B zones --> B cell dominant but also T cell rich
- Center around FDCs
2. Covered by follicle associated epithelium
3. No afferent lymph
4. No capsule

21

Where is IgA secreted by plasma cells?

Lamina propria as the effector site!
- High B cell population!!

22

What is the difference between IgA1 & IgA2?

IgA1 = monomeric
- Found in CIRCULATION
- No secretory piece
IgA2 = sIgA = dimeric
- More resistant to proteolysis
- In intestine & female repro - SECRETED
@ GI: 2 > 1
@ respiratory tract: 1 > 2

23

Which cytokine helps B cell switching in the mucosa?

TGF beta

24

How can you tell mucosal IgA from plasma IgA?

Mucosal has secretory piece from transport with poly-Ig receptor!

25

Describe the 4 step T dep pathway of IgA induction. Where does this occur?

Where: peyer's patches only
1. Ag+APC
2. APC activated Th cells
3. Th cells stimulate IgM/D B cells via:
- CD40L
- TGF beta --> push to IgA B cells
4. with retinoic acid in the LP, B cells --> plasma cells
IgA =
- HIGH affinity
- Monoreactive
- Vs. pathogens & toxins

26

Describe the T INdep pathway of IgA induction. Where does this occur?

Where: peyers patches & isolated lymphoid follicles
1. DC directly initiates class switch of B cells via:
- TGF beta
- Retinoic acid
- NO, BAFF, APRIL

27

What kind of IgA is produced by T dep pathway?

- HIGH affinity
- Monoreactive
- Vs. pathogens & toxins

28

What kind of IgA is produced by T INdep pathway?

Low affinity
Polyreactive
Vs. commensals

29

Which cytokines are produced by epithelium for B cell differentiation into plasma cells? For B cell switching to IgA?

Into plasma cells:
IL 4
5
6
10
IgA class switch = TNF beta

30

How is IgA transported into the epithelium?

Poly Ig receptor binds J chain on IgA Ab
Secreted IgA has piece of receptor attached to it = secretory component

31

What is the role of IgA? Can it generate a complement reaction?

Prevent attachment of bacteria & viruses to mucous membranes
Binds intracellular pathogens of epithelium
*Anti-inflammatory*
NO complement reactions

32

What is the second most common Ab found in mucous secretions? What receptor moves this Ab?

IgG for neutralization
Via FcRn

33

What membrane proteins do SI T cells express (what does each bind at the SI target site)? Colon?

SI T cells have a4b7 & CCR9
- a4b7 binds MAdCAM1 @ lamina propria
- CCR9 binds CCL25 @ epithelial cells
Colon T cells have CCR10

34

Where are intra-epithelial lymphocytes? What is their function?

Between epithelial cells
Mostly CD8 cells --> kill infected cells

35

Which cytokines drive the development of intra-epithelial lymphocytes?

IL 7 & 15 --> development

36

How is mucosal tolerance created? Name the 3 major parts.

1. Intestinal epithelial cells
- Stimulated by commensals
- Make retinoic acid for TOLERANCE
2. CD103 DC & CX3CR1 macrophages @ lamina propria
- Stimulated by microbiota
- Make TGF beta, RA & IL10
= anti-inflam
3. Foxp3+ regulatory T cells
- On when you start making IgA & IL2
- Inhibitory Tregs

37

How does retinoic acid act on DCs?

Primes them!
DCs:
- ↑ CD103
- ↑RA production --> Th17 cells
- ↑TGF beta --> development of Foxp3 Tregs

38

What additional cytokine signals are present to create mucosal inflammation?

IL15!

39

When +IL15, how do dendritic cell cytokine secretions change? What other cell is activated?

CX3CD1 macrophages also activated
DCs:
- More RA --> ↑Th17
- More IL 12 --> ↑Th1
- No longer making TGF beta
NET: inflammation

40

What is the signal that microbiota create that is critical for healthy mucosa?

IL10
sIgA production via ↑AID
RA --> ↑Treg activity

41

How is vitamin A as retinoic acid important for get T and B cells?

Imprints T & B cells to be gut specific
↑s B cell IgA specificity

42

What patient populations (GI auto-immunity) are reported to be vitamin D deficient? What role does vit D play in mucosal immunity?

IBD & colitis patients
Decreases Th1 & Th17
Increases Treg
Inhibits DC differentiation

43

How to mucosal vaccines work?

Goal = ↑sIgA & local T cells
How deliver polio & cholera vaccines