Immunology of the gut

Question 1

Examples of PRRs:

Answer 1

Toll-like receptors (TLR4, TLR5)

NODs (NOD2)

Question 2

What arm of the immune system are PPRs involved in?

Answer 2

Innate

Question 3

CD4+ cells can form 2 main arms:

Answer 3

Effector cells

Regulator cells

Question 4

Effects CD4+ cells

Answer 4

Th1
Th2
Th17

Question 5

Th1 cells -

Answer 5

Release INF-y

Involved in intracellular pathogens, chronic inflammation, autoimmunity

Question 6

Th2 cells -

Answer 6

IL-4
IL-5
Involved in allergy and asthma

Question 7

Th17 cells

Answer 7

Il17

Extracellular pathogens, chronic inflammation and autoimmunity

Question 8

What released TNF-a

Answer 8

Activated macrophages

Question 9

What amount of the body’s lymphocytes are in mucosal surfaces?

Answer 9

3/4ths

Question 10

Defences of the intestinal epithelial cell barrier:

Answer 10

Tight junctions between cells
Goblet cells - mucins
Paneth cells - anti-microbial peptides

Question 11

What secretes anti-microbial peptides?

Answer 11

Paneth cells

Question 12

MALT =

Answer 12

Mucosal-associated lyphoid tissue

Question 13

Types/subsets of MALT:

Answer 13

NALT
BALT
GALT

Question 14

Where are most commensals in the gut found?

Answer 14

Colon

Question 15

Important tasks of GALT:

Answer 15

Ignore harmless antigens, food, commensals

Mount an immune response to pathogens

Question 16

GALT can be arranged in:

Answer 16

Organised tissues

Scattered lymphoid tissue

Question 17

Organised tissues in GALT:

Answer 17

Peyers patch
Isolated lymphoid follicles
Mesenteric lymph node

Question 18

Peyer’s patch is found in

Answer 18

Small intestine

Question 19

Isolated lymphoid follicles are found in

Answer 19

Small and large intestine

Question 20

Mesenteric lymph node drains

Answer 20

Entire intestinal tract

Question 21

Scatter lymphoid cells in GALT:

Answer 21

Lamina propria leukocytes

Intra-epithelial lymphocytes

Question 22

2 ways antigens at mucosal surface can be transported across epithelial barrier:

Answer 22

1. M cells

2. Capture by macrophages/APCs

Question 23

M cells =

Answer 23

Microfold cells

Question 24

M cells are found on

Answer 24

Peyers patch

Isolated lymphoid follicles

Question 25

Ex of pathogens which use M cells to gain access:

Answer 25

Polio Reavirus Salmonella Shingella

Question 26

How can antigens be captures from the intestinal lumen?

Answer 26

Macrophages have porcesses which extend to capture - hand over to DCs - drain to MLN

Question 27

To happens to dendritic cells to regulate immune function

Answer 27

Conditioning

Question 28

What can condition DCs

Answer 28

``` Diet Epithelial cells Flora Vitamins Cytokines ```

Question 29

What is conditioning?

Answer 29

Makes DCs favour a Tref response

Question 30

T reg cells

Answer 30

Treg1 Treg3 CD25+

Question 31

Treg1 released

Answer 31

IL-10

Question 32

Treg3 releases

Answer 32

TGF-b

Question 33

CD25+ released

Answer 33

IL-10, TGF-b

Question 34

How can microbial metabolites control the gut inflammatory response.

Answer 34

Short chain fatty acids - make DCs favour regulatory response - make macrophages less responsive to TLRs/LPS entering the gut.

Question 35

What can interrupt intestinal homeostasis?

Answer 35

Too many effects | Regulatory cell defect

Question 36

Dominant antibody of mucosal system =

Answer 36

IgA

Question 37

Difference between blood and GALT IgA

Answer 37

``` Blood = monometric GALT = dimetric ```

Question 38

Dimetric IgA is joined by

Answer 38

J chain

Question 39

why is J chain important?

Answer 39

Binds to poly-IgA receptor Most is cleaved, some is left to make secretory component Secretory component binds to mucus layer

Question 40

Functions of sIgA

Answer 40

- Prevents adherence of microorganisms | - Neutralises toxins

Question 41

Why is IgA better than IgG?

Answer 41

IgA has little capacity to opsonise or start classical pathway of complement

Question 42

What can replace sIgA in those deficient?

Answer 42

sIgM

Question 43

What normal is generated when food antigens are consumed:

Answer 43

Oral tolerance

Question 44

Oral tolerance:

Answer 44

Antigen specific T effector cells turned off or deleted | Antigen specific T regulatory cells generated

Question 45

What happens when commensals are in gut?

Answer 45

Treg response | Ignored by systemic immune response

Question 46

What happens when pathogens present in gut?

Answer 46

DCs activated through PRRs and induce effector cells.

Question 47

How does the body tell the difference between commensals and pathogens?

Answer 47

1. Localisation of PPRs 2. Virulence factors in pathogens 3. Commensals avoid PRR activation

Question 48

TLR4 is found

Answer 48

Crypt base

Question 49

TLR5 is found

Answer 49

Basolateral side

Question 50

Genetic predisposition associated with Crohn's =

Answer 50

NOD2

Question 51

Example of aminosalicylates

Answer 51

Sulphasalazine

Question 52

Examples of immune suppressants used in IBD

Answer 52

Azathiprine | Methotrexate

Question 53

Examples of biologicals used in IBD:

Answer 53

Infliximab | Adalimumab