alimentary immune functions

Question 1

why is the epithelium of the digestive tract an external environment

Answer 1

possible for bacteria to reach without crossing a membrane

Question 2

distribution of microbiota in alimentary tract (mouth; stomach; duodenum, jejunum, ileum; caecum, colon)

Answer 2

mouth: lots as put in lots of dirty things; stomach: not many as low pH; duodenum, jejunum, ileum: low due to paneth cells and Peyer’s patches; caecum, colon: huge increase)

Question 3

4 main mechanisms of protection against infection in gastrointestinal mucosa

Answer 3

physical barriers, chemical barriers, bacteria protection, immunological

Question 4

5 physical barrier mechanisms

Answer 4

tight epithelial wall, glycocalyx, mucous, unstirred layer, peristalsis

Question 5

2 chemical barrier mechanisms

Answer 5

bacteriacidal enzymes from paneth cells, acid from stomach

Question 6

bacteria protection mechanism

Answer 6

commensal bacteria maintain immune system priming and may attack foreign species

Question 7

what is mucosa-associated lymphoid tissue (MALT) rich in

Answer 7

T and B cells

Question 8

2 categories of mucosa-associated lymphoid tissue (MALT)

Answer 8

GALT (gut-associated lymphoid tissue), BALT (bronchus-associated lymphoid tissue)

Question 9

how can GALT (gut-associated lymphoid tissue) be split into 2 categories

Answer 9

organisation (organised and disorganised)

Question 10

what are examples of organised GALT (gut-associated lymphoid tissue)

Answer 10

Peyer’s patches in small intestine, lymphocytes in mesenteria lymph nodules (where lymph from villi drain)

Question 11

what are examples of disorganised GALT (gut-associated lymphoid tissue)

Answer 11

lymphocytes in lamina propria (mainly IgA-secreting B-cells), lymphocytes in space below baseolateral membrane of epithelium (intra-epithelial cells)

Question 12

what can also phagocytose bacteria in the liver

Answer 12

Kuppfer cells

Question 13

what do Peyer’s patches consist of

Answer 13

aggregated lymphoid follicles covered with follicle associated epithelium (FAE)

Question 14

where are Peyer’s patches found

Answer 14

small intestine (most abundant in distal ileum)

Question 15

function of Peyer’s patches

Answer 15

immune sensors as capable of monitoring local bacteria; provide protection against pathogenic bacteria

Question 16

what is the development of Peyer’s patches dependent on

Answer 16

exposure to bacterial flora

Question 17

numbers of Peyer’s patches by last trimester and maximum in teenage years

Answer 17

50, 250

Question 18

what are Peyer’s patches rich in

Answer 18

B cells, T cells, macrophages, dendritic cells

Question 19

what does follicle associated epithelium (FAE) overyling dome structure of Peyer’s patches contain

Answer 19

M cells (specialised enterocytes without surface microvilli; instead contain microfold on apical membrane); has reduced number of goblet cells and enterocytes

Question 20

main function of M cells

Answer 20

perform transcytosis of luminal bacteria, antigens and proteins

Question 21

what is transcytosis

Answer 21

transcellular transport in which various macromolecules are captured by exocytosis, transported across the interior of a cell, and out the invaginated basolateral membrane via vesicles to infiltrating lymphocytes

Question 22

why do M cells express IgA receptors

Answer 22

they facilitate transfer of IgA-bacteria complex into Peyer’s patches

Question 23

what also assists in antigen uptake besides M cells

Answer 23

dendritic cells which capture particles for M cells (present in sub-epithelial dome along with naive B, T cells and macrophages)

Question 24

fate of antigens

Answer 24

presented to lymphocytes in Peyer’s patches for assessment and potential immunological response

Question 25

fate of activated lymphocytes

Answer 25

develop gut homin markers and migrate to mesenteric lymph nodes for proliferation

Question 26

how is the apical membrane of M cells specialised for its function

Answer 26

no glycocalyx or membrane hydrolytic enzymes

Question 27

what can M cells also produce

Answer 27

pro-inflammatory cytokine interleukin 1

Question 28

fate of cells on villous side of crypt during embryonic and postnatal development

Answer 28

differentiate into absorptive enterocytes, goblet cells, enteroendocrine cells

Question 29

fate of cells on FAE side of crypt during embryonic and postnatal development

Answer 29

differentiate into absorptive enterocytes, M cells, rarely goblet cells

Question 30

susceptibility of M cells

Answer 30

suceptible to pathogens as ability to transcytose and accessible

Question 31

what is the most abundant antubody in the body (not just circulating)

Answer 31

IgA

Question 32

why is IgA the most abundant antibody

Answer 32

highly prevalent in mucosal secretions because MALT is associated with large numbers of IgA+ B cells

Question 33

structure of secretory IgA (SIgA)

Answer 33

dimeric form of IgA

Question 34

where is SIgA produced and fate

Answer 34

by B cells in lamina propria and transported across enterocyte to be secreted into interstitial space

Question 35

what binds both IgA molecyles together in plasma (B) cells

Answer 35

J-chain

Question 36

what does the IgA dimer bind to

Answer 36

special receptor on external basolateral surface of enterocytes (polymeric immunoglobulin receptor, pIgR)

Question 37

what does the pIgR (receptor) become and subsequently bind to to form SIgA

Answer 37

becomes secretory component and binds to length of IgA dimer, becoming SIgA

Question 38

fate of SIgA

Answer 38

endocytosed into the epithelial cell, actively transported within vesicle to apical membrane, exocytosed into gut lumen

Question 39

what are the functions of the secretory component

Answer 39

help IgA move through enterocyte, protect antibody dimer from enzymatic and acidic degradation

Question 40

when SIgA bind to pathogens, what do they prevent

Answer 40

pathogens adhering to mucosal wall

Question 41

what is antigen-specific SIgA production stimulated by

Answer 41

M cells and dendritic cells in Peyer's patches

Question 42

fate of stimulated mucosal lymphocytes in Peyer's patches

Answer 42

migrate into local mesenteric lymph nodes and drain into lymphatic system

Question 43

how do lymphocytes reach systemic circulation before spreading throughout body in blood

Answer 43

via thoracic duct

Question 44

what is lymphocyte homing

Answer 44

lymphocytes remaining in blood until activated by tissue-sepecific endothelial adhesion molecules at site of inflammation, allowing transmigration of lymphocytes into gut mucosa

Question 45

what does lymphocyte homing require

Answer 45

specialised post-capillary microvascular endothelial cells, such as high endothelial venules (HEVs) of lymphoid tissue

Question 46

what is constitutively expressed on surface of lymphocytes

Answer 46

L-selectin (carbohydrate-binding lectin)

Question 47

function of L-selectin

Answer 47

mediates low adhesive interactions that enable leukocytes to roll in postcapillary venules and HEVs

Question 48

how does L-selectin mediate lymphocyte rolling in HEVs

Answer 48

binds to mucosal addressin cell adhesion molecule-1 (MAdCAM-1)

Question 49

where is MAdCAM-1 constitutively expressed

Answer 49

HEVs of Peyer's patches and mesenteric lymph nodes; flattened endothelial cells localised in lamina propria of small and large intestine (enabling lymphocyte recruitment in chronic gut inflammation)

Question 50

diagram of lymphocyte circulation

Answer 50

diagram