T1 L11 Mucosal immunity

Question 1

What is mucosa-associated lymphatic tissue divided into?

Answer 1

Bronchial associated lymphatic tissue (BALT)

Gut associated lymphatic tissue (GALT)

Question 2

Why is the mucosal immune system important?

Answer 2

Largest immune compartment of organism
In direct contact with outside environment
Mucosal sites are port of entry for many infections and target site for vaccine-induced protection

Question 3

What is the estimated surface area of the mucosal immune system?

Answer 3

400m2

Question 4

What are the HIV transmission routes?

Answer 4

Genitourinary
Rectal
Oral

Question 5

What are the main mucosal defence strategies of the mucosa and oropharynx?

Answer 5

Endogenous flora
Epithelium and mucus
Regionalised immune system and gut homing of B and T cells
Lymphoid complexes along GI tract

Question 6

Describe the adaptions of the epithelium and mucus

Answer 6

Mechanical barriers - cells and tight junctions
Specialised epithelial cells - goblet cells, absorptive epithelial cells, M cells, paneth cells
Antimicrobial substances
Mucins form viscous barrier

Question 7

What are mucins?

Answer 7

Extensively glycosylated proteins

Question 8

What are some antimicrobial substances?

Answer 8

Defensins
Lysozymes
Lactoferrin
Phospholipases

Question 9

Where is the greater and least amount of lymphoid tissue found along the GI tract?

Answer 9

Greatest in oropharynx and terminal ileum

Least in small and large bowel

Question 10

What are some intestinal epithelial cells?

Answer 10

Goblet cells
Epithelial cells
M cells
Paneth cells

Question 11

What do goblet cells do?

Answer 11

Produce mucus to form physical-chemical barrier

Question 12

What do epithelial cells do?

Answer 12

Express TLRs

Question 13

What does surface TLR ligation lead to?

Answer 13

Tightening of epithelial junctions
Increased proliferation
Increased epithelial motility
Enhance barter function

Question 14

What do M cells do?

Answer 14

Transport antigens to subepithelial lymphoid structures

Question 15

What do Paneth cells produce?

Answer 15

Human defensin 5 (HD5) precursor
HD6 precursor
Trypsin which activates HD5 and HD6

Question 16

What do Peyer’s patches contain?

Answer 16

Germinal centre for B and T cells

Question 17

Where are Peyer’s patches located?

Answer 17

In distal ileum in areas of follicle-associated epithelium (FAE)

Question 18

How many Peyer’s patches are there?

Answer 18

Before 30 weeks gestation, the foetus has 60

Reaches maximum of 240 by puberty

Question 19

What are the 3 main domains of Peyer’s patches?

Answer 19

Follicular areas
Interfollicular areas
Follicle-associated epithelium

Question 20

How does follicle-associated epithelium differ from normal epithelium?

Answer 20

Due to microvilli regularity and length

Presence of infiltrating immune cells

Question 21

What do the follicular areas of Peyer’s patches contain?

Answer 21

Proliferating B-lymphocytes
Follicular dendritic cells
Macrophages

Question 22

What do the interfollicular areas of Peyer’s patches contain?

Answer 22

Proliferating B-lymphocytes
Follicular dendritic cells
Macrophages

Question 23

How are Peyer’s patches connected to circulation?

Answer 23

By endothelial venues (from blood to PP) and lymphatic vessels (from PP to mesenteric lymph nodes)

Question 24

What are the features of M cells?

Answer 24

Small microvilli
Large cell membrane fenestrations
Trans-cellular transport of antigen
Exocytosis at basolateral membrane

Question 25

How many M cells per Peyer's patch?

Answer 25

100 to 150

Question 26

Where are mesenteric lymph nodes located?

Answer 26

At base of mesentery

Question 27

What do mesenteric lymph nodes do?

Answer 27

Collect lymph, cells and antigens from intestinal mucosa

Question 28

What is the main site for oral tolerance induction?

Answer 28

Mesenteric lymph nodes

Question 29

Describe the IEL in the basolateral part of epithelium

Answer 29

Irregular shape - long extensions in close contact with neighbouring epithelial cells Occur in variable numbers along gut

Question 30

What are the 3 groups that intraepithelial T cells can be divided into?

Answer 30

TCRaB+CD8aB+ TCRaB+CD4aB+ TCRaB+CD8aa+

Question 31

What are MIC-A and MIC-B?

Answer 31

Ligands for NK cell activating receptor NKG2D

Question 32

What is T-cell differentiation influenced by?

Answer 32

Epithelial cells and dendritic cells

Question 33

What are Treg cells important in?

Answer 33

Establishing and maintaining food tolerance and class switch including TGF-B and others

Question 34

What do Th1 cells do?

Answer 34

Produce IFN-gamma | Important in killing virally infected epithelial cells

Question 35

What do Th2 cells do?

Answer 35

Induced by worm infection | Produce IL-4 and IL-113 which increase fluid secretion, mucus secretion, bowel motility and smooth muscle contraction

Question 36

What do Th17 cells do?

Answer 36

Produce IL-17 and IL-22 | Cytokines interact with receptors on epithelial cells to regulate production of mucins or defensins

Question 37

What do dendritic cells do?

Answer 37

In lamina propria Long extensions that reach through epithelium to sample contents of intestinal tube Antigens get presented to T cells

Question 38

Describe the protection of secretory IgA against epithelial invasion

Answer 38

Cross-reactive innate-like (low affinity) and infection or vaccine induced specific (high affinity) protection

Question 39

What do pIgA and pIgM do?

Answer 39

Exert non-inflammatory effects inside and below epithelium Neutralisation of virus or endotoxin Antigen excretion

Question 40

Describe IgA antibody

Answer 40

IgA against food antigens provides immune exclusion IgA weakly activates complement system Secretion of IgA coupled to J chain depends on trans-cellular transport mechanisms

Question 41

How do activated T cells and circulating memory cells exit the lymph nodes?

Answer 41

Via efferent lymphatics Return to circulation through thoracic duct Reach target tissues via blood stream

Question 42

What guides effector cells to different tissues?

Answer 42

Different combinations of homing receptors | At the tissue, up regulation of respective ligand molecule is related to the situation in the tissue

Question 43

What are the inductions sites?

Answer 43

Peyer's patches | Mesenteric lymph nodes

Question 44

What does priming in the induction sites lead to?

Answer 44

Expression of a4B7 and CCR9 (homing receptors)

Question 45

What do homing receptors do?

Answer 45

Facilitate migration from blood to effector sites

Question 46

What are the effector sites?

Answer 46

Lamina propria | Gut epithelium

Question 47

What type of cells does IEL include?

Answer 47

Treg Th1 Th2 Th17

Question 48

Why are regulatory T-cell responses important in regard to food antigens?

Answer 48

Absorption of nutrients and inflammation are incompatible