alimentary immune functions Flashcards

immunology: recall the main immunological processes associated with Peyer's patches & gut immunology, including the role of M-cells and dendritic cells, and the purpose of lymphocyte homing and circulation

1
Q

why is the epithelium of the digestive tract an external environment

A

possible for bacteria to reach without crossing a membrane

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2
Q

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

A

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)

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3
Q

4 main mechanisms of protection against infection in gastrointestinal mucosa

A

physical barriers, chemical barriers, bacteria protection, immunological

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4
Q

5 physical barrier mechanisms

A

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

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5
Q

2 chemical barrier mechanisms

A

bacteriacidal enzymes from paneth cells, acid from stomach

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6
Q

bacteria protection mechanism

A

commensal bacteria maintain immune system priming and may attack foreign species

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7
Q

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

A

T and B cells

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8
Q

2 categories of mucosa-associated lymphoid tissue (MALT)

A

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

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9
Q

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

A

organisation (organised and disorganised)

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10
Q

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

A

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

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11
Q

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

A

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

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12
Q

what can also phagocytose bacteria in the liver

A

Kuppfer cells

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13
Q

what do Peyer’s patches consist of

A

aggregated lymphoid follicles covered with follicle associated epithelium (FAE)

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14
Q

where are Peyer’s patches found

A

small intestine (most abundant in distal ileum)

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15
Q

function of Peyer’s patches

A

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

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16
Q

what is the development of Peyer’s patches dependent on

A

exposure to bacterial flora

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17
Q

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

A

50, 250

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18
Q

what are Peyer’s patches rich in

A

B cells, T cells, macrophages, dendritic cells

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19
Q

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

A

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

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20
Q

main function of M cells

A

perform transcytosis of luminal bacteria, antigens and proteins

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21
Q

what is transcytosis

A

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

22
Q

why do M cells express IgA receptors

A

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

23
Q

what also assists in antigen uptake besides M cells

A

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

24
Q

fate of antigens

A

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

25
Q

fate of activated lymphocytes

A

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

26
Q

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

A

no glycocalyx or membrane hydrolytic enzymes

27
Q

what can M cells also produce

A

pro-inflammatory cytokine interleukin 1

28
Q

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

A

differentiate into absorptive enterocytes, goblet cells, enteroendocrine cells

29
Q

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

A

differentiate into absorptive enterocytes, M cells, rarely goblet cells

30
Q

susceptibility of M cells

A

suceptible to pathogens as ability to transcytose and accessible

31
Q

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

A

IgA

32
Q

why is IgA the most abundant antibody

A

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

33
Q

structure of secretory IgA (SIgA)

A

dimeric form of IgA

34
Q

where is SIgA produced and fate

A

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

35
Q

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

A

J-chain

36
Q

what does the IgA dimer bind to

A

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

37
Q

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

A

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

38
Q

fate of SIgA

A

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

39
Q

what are the functions of the secretory component

A

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

40
Q

when SIgA bind to pathogens, what do they prevent

A

pathogens adhering to mucosal wall

41
Q

what is antigen-specific SIgA production stimulated by

A

M cells and dendritic cells in Peyer’s patches

42
Q

fate of stimulated mucosal lymphocytes in Peyer’s patches

A

migrate into local mesenteric lymph nodes and drain into lymphatic system

43
Q

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

A

via thoracic duct

44
Q

what is lymphocyte homing

A

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

45
Q

what does lymphocyte homing require

A

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

46
Q

what is constitutively expressed on surface of lymphocytes

A

L-selectin (carbohydrate-binding lectin)

47
Q

function of L-selectin

A

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

48
Q

how does L-selectin mediate lymphocyte rolling in HEVs

A

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

49
Q

where is MAdCAM-1 constitutively expressed

A

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)

50
Q

diagram of lymphocyte circulation

A

diagram