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Immunology > L13 > Flashcards

L13 Flashcards

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?

A

TGF beta

Retinoic acid

19
Q

Explain the function of retinoic acid.

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?

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?

A

Lamina propria as the effector site!

- High B cell population!!

22
Q

What is the difference between IgA1 & IgA2?

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?

A

TGF beta

24
Q

How can you tell mucosal IgA from plasma IgA?

A

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

25
Q

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

A 
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
Q

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

A

Where: peyers patches & isolated lymphoid follicles

  1. DC directly initiates class switch of B cells via:
    - TGF beta
    - Retinoic acid
    - NO, BAFF, APRIL
27
Q

What kind of IgA is produced by T dep pathway?

A
  • HIGH affinity
  • Monoreactive
  • Vs. pathogens & toxins
28
Q

What kind of IgA is produced by T INdep pathway?

A

Low affinity
Polyreactive
Vs. commensals

29
Q

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

A 
Into plasma cells:
IL 4
5
6
10
IgA class switch = TNF beta
30
Q

How is IgA transported into the epithelium?

A

Poly Ig receptor binds J chain on IgA Ab

Secreted IgA has piece of receptor attached to it = secretory component

31
Q

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

A

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

32
Q

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

A

IgG for neutralization

Via FcRn

33
Q

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

A

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

34
Q

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

A

Between epithelial cells

Mostly CD8 cells –> kill infected cells

35
Q

Which cytokines drive the development of intra-epithelial lymphocytes?

A

IL 7 & 15 –> development

36
Q

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

A
  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
Q

How does retinoic acid act on DCs?

A 
Primes them! 
DCs:
- ↑ CD103
- ↑RA production --> Th17 cells
- ↑TGF beta --> development of Foxp3 Tregs
38
Q

What additional cytokine signals are present to create mucosal inflammation?

A

IL15!

39
Q

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

A 
CX3CD1 macrophages also activated
DCs:
- More RA --> ↑Th17
- More IL 12 --> ↑Th1 
- No longer making TGF beta
NET: inflammation
40
Q

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

A

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

41
Q

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

A

Imprints T & B cells to be gut specific

↑s B cell IgA specificity

42
Q

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

A

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

43
Q

How to mucosal vaccines work?

A

Goal = ↑sIgA & local T cells

How deliver polio & cholera vaccines

Immunology (25 decks)

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