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L13 Flashcards

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1
Q

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

A

M cells

Trans-epithelial DCs

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2
Q

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

A

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

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3
Q

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

A 
1. Inductive site
BALT = bronchus 
GALT = gut
NALT = nasopharinx
2. Effector site = lymphocytes @ epithelium & lamina propria
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4
Q

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

A 
Break/transport across epithelium
B/G/NALT 
Lymph
Local lymph nodes
Thoracic duct 
Blood 
Back to respective epithelium/LP
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5
Q

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

A
  1. ILF = isolated lymphoid follicle
    - No distinct T/B zones in germinal centers–> mostly B cells
    - THROUGHOUT GI tract
  2. Peyer’s patch
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6
Q

Describe the characteristics of follicle associated epithelium.

A

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

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7
Q

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

A

B cells!

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8
Q

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

A

Outer layer - contains microbes

Inner layer - sterile with antimicrobials (defensins) & Abs

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9
Q

What junctions hold together epithelial cells?

A

Tight jxns

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10
Q

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

A

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

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11
Q

What are paneth cells? Where do you find them?

A

@ bottom of intestinal crypts

Make defensins

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12
Q

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

A

@ bottom of intestinal crypts

Constant replenishment of epithelial cells –> upward migration

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13
Q

What surface receptors do epithelial cells express?

A

TLR

MHC 1 & 2

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14
Q

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

A

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

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15
Q

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

A

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

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16
Q

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

A

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

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17
Q

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?

A
  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
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18
Q

What cytokines do epithelial cells secrete to increase Treg maturation?

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A

TGF beta

Retinoic acid

19
Q

Explain the function of retinoic acid.

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A

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

20
Q

What are 4 main characteristics of Peyer’s patches?

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A
  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
Q

Where is IgA secreted by plasma cells?

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A

Lamina propria as the effector site!

- High B cell population!!

22
Q

What is the difference between IgA1 & IgA2?

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A 
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
Q

Which cytokine helps B cell switching in the mucosa?

24
Q

How can you tell mucosal IgA from plasma IgA?

Study These Flashcards
A

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

Immunology (25 decks)

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