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MIIM20002 - Microbes, Infections, Responses > Lecture 13 - Mucosal Immunity > Flashcards

Lecture 13 - Mucosal Immunity Flashcards

1
Q

What are the components of the mucosal immune system?

A
  • GIT
  • Respiratory tract
  • Urogenital system
  • Breast tissue
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2
Q

What is MALT?

A

Mucosal associated lymphoid tissue

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3
Q

What is GALT?

A

Gastrointestinal associated lymphoid tissue

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4
Q

What is the structure of the GIT epithelium?

A
  • Villi made up of enterocytes
  • Goblet cells
  • Brush border forming microvilli on enterocytes
  • Blood supply, lymphatics
  • Peyer’s patches
  • Lamina propria
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5
Q

What does the epithelium of the GIT potentially experience much immune stimulation?

A

Because around 100g of protein passes through our gut daily

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6
Q

What is the function of the distal end of the villous?

A

Absorption

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7
Q

What is the function of the proximal end of the villous?

A

Secretion

Division

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8
Q

What types of cells are there in the gut epithelium?

A 
Goblet
Enterocytes
Paneth cells
M cells
Intra-epithelial lymphocytes
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9
Q

What is the function of goblet cell?

A

Secrete:
• mucin
• lysozyme
• lactoferrin

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10
Q

What is the function of Paneth cells?

A

Secrete:

• defensins

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11
Q

Where are the lymphocytes in the villi located?

A

In the lamina propria

In between the enterocytes: intraepithelial lymphocytes (IEL)

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12
Q

What are the pros / cons of a large surface area of the gut epithelium?

A

Pro: lots of area for secretion / absorption

Cons:
• vulnerability to microbes
• vulnerability to food antigens

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13
Q

What is thus the general goal of the GALT?

A

Dampen down the immune response

Tolerance of harmless non-self antigens

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14
Q

What are the innate defences of the gut?

A
  • Peristaltic flushing action
  • Acid
  • Mucous
  • Tight junctions
  • Antimicrobial factors
  • Cytokines / chemokines
  • Cells (lymphocytes, macrophages)
  • Glycocalyx
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15
Q

What are the physical and chemical barriers of the surface of the gut?

A

Glycocalyx

Mucin

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16
Q

In general, how does the mucosal immune system vary from the systemic immune system?

A

Systemic: structure
Mucosal: not overly structured

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17
Q

Compare the antigen sampling in lymph nodes of the systemic and mucosal IS

A

Systemic: antigen draining from tissue

Mucosal: direct sampling, lymphocytes present in the tissue

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18
Q

Compare the lymph nodes in systemic and mucosal

A

Systemic: capsulated, must enter by afferent lymphatics

Mucosal: not encapsulated, antigen may be sampled directly from the lumen of the gut

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19
Q

Where are M cells found?

A

At the tip of the Peyer’s patch

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20
Q

What is the structure of a Peyer’s patch?

A

M cell
SED: sub-epithelial dome
Follicles

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21
Q

Where do lymphocytes become activated in the Peyer’s patch?

A

The follicle

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22
Q

In the mucosa, where are the two places that lymphocytes are found?

A
  • Effector site, IEL

* Follicle of Peyer’s patch

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23
Q

What is the name for the enterocytes on the Peyer’s patch?

A

Follicle associated epithelium

24
Q

Which cells sample the contents of the lumen in the Peyer’s patches? Where are these cells located?

A

• M cells
present at tip of dome

• APCs
present in the SED

25
Q

Do all cells of the gut have microvilli?

A

No the M cells don’t

26
Q

Describe the structure of the M cell

A
  • No microvilli
  • No glycocalyx
  • No mucin
  • No MHC II –> not an APC
27
Q

Describe the function of M cells

A
  1. Sample anitgen from lumen by phagocytosis

2. Antigen delivered to APCs in the SED

28
Q

Where are APCs located in the mucosa?

A
  • SED

* Lamina propria

29
Q

What is the lamina propria?

A

Loose connective tissue under the GIT epithelium

Contains APCs and Lymphocytes

30
Q

What happens once denritic cell take up antigen?

A

Move to:
• Follicle
• Mesenteric lymph node

to present the antigen to T cells

31
Q

Which T cells are most often induced in mucosal immunity?

What are the functions of these Th cells?

A

Treg (dampening)

Th2 (antiviral)

32
Q

Which isotype is favoured in mucosal immunity?

A

Secretory IgA

33
Q

How are T lymphocytes trafficked back to the mucosa?

A
  1. DCs induce expression of integrin a4B7 and receptors for mucosal chemokines on lymphocytes
    2a. a4-B7 binds to MAdCAM1 on mucosal endothelium
    2b. Lymphocytes binds the mucosal chemokines and undergo chemotaxis
34
Q

What is MAdCAM1 and what does it bind to?

Where is MAdCAM1 present?

A

It is an addressin

It is found on the endothelium (capillaries) of the GIT

It binds to a4-B7 integrin on lymphocytes

35
Q

Where are naive lymphocytes activated in the mucosa?

A
  1. Follice of Peyer’s patches

2. Mesenteric lymph node

36
Q

What happens when a DC in the Lamina Propria takes up antigen?

A
  1. Migrates to Mesenteric lymph node

2. Presents antigen to naive lymphocytes

37
Q

What is the effector site of the GALT?

A

The lamina propria / villus

38
Q

What happens back at the effector site?

A
  • B cells produce IgA
  • CD8+ cells protect against intracellular infections
  • CD4+ cells: regulation
39
Q

Where do lymphocytes go once activated?

A
  1. Drain from Mesenteric lymph node to thoracic duct
  2. Re-enter circulation
  3. Circulate back to site of infection (GIT), as well as the rest of the gut epithelium
  4. At site of infection, they are selected out of the blood stream by MAdCAM1 and a4 B7 interactions and chemokines
40
Q

What happens to activated B cells?

A
  1. Enter blood
  2. Return to effector sites
  3. Make and secrete IgA into lumen
41
Q

What is the structure of secretory IgA?

A
  • Dimer
  • J chain
  • Secretory component
42
Q

What is the structure of IgA in the blood?

A

Monomer

43
Q

What is the structure of secretory IgM?

A

Pentamer

44
Q

Describe the process of secretion of IgA?

A
  1. IgA binds to pIgR on basal surface of enterocyte
  2. Endocytosis
  3. Transcytosis
  4. Exocytosis with some of secretory component still attached
45
Q

What is the structure of the secretory component?

A

It is part of the pIgR that was on the basal surface of the enterocyte that didn’t get cleaved

46
Q

What is the function of the secretory component?

A

Prevents proteolysis of the IgA

47
Q

What is the function of sIgA? (5)

A
  • Blocking epithelial attachment of bacteria
  • Neutralisation of toxins
  • Neutralisation of intracellular antigens
  • Transcytosis of antigen in lamina propria into the lumen

(• weak opsonin, however)

48
Q

Describe how toxin in the lamina propria may be neutralised

A
  1. IgA in the lamina propria binds the toxin
  2. IgA binds to pIgR and is transcytosed across the cell with the toxin
  3. Toxin + IgA dumped into lumen
49
Q

How are T cells skewed towards Treg, Th2 and Th17?

A

TGF-beta

50
Q

What are the protective factors of the respiratory tract?

A
  • Mucociliary elevator
  • Surfactant containing microbicidals

No mucus, however

51
Q

What is the function of surfactant?

A
  • Binds and removes pathogens

* reduces surface tension in the alveoli

52
Q

Where are the inductive sites of the respiratory tract?

What does this mean?

A
  • Adenoids
  • Tonsils

Here, there are M cells that sample antigen and lead to activation of the adaptive immune response

53
Q

Where are the effector sites of the respiratory system?

A
  • Salivary glands
  • Lacrimal glands
  • Bronchi
54
Q

What does tolerogenic mean in reference to MALT?

A

It means that the predominant response of the immune response is suppressive, not reactive

55
Q

Describe the mucous in the respiratory tract

A

No mucous

Think about it: it would clog the alveoli and make it ineffective for gas exchange

56
Q

What is the role of enterocytes in the immune response?

A
  • cytokine production (TGF-beta)

* defensin production

57
Q

What are the antimicrobial compounds found in the gut?

A
  • Lactoferrin
  • Bile salts
  • Complement
  • Defensins

MIIM20002 - Microbes, Infections, Responses (32 decks)

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