Barrier Immunology in the Gut Flashcards

1
Q

Different cytokines secreted by T-helper cells will induce ________

A

Class switching

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2
Q

What does Th1 secrete? what does it stimulate?

A
  • Secretes: IFN-gamma
  • Class switching to IgG subtypes, macrophage activation, CT cell activation
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3
Q

TGF-beta and retinoic stimulate class switching to what?

A

IgA

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4
Q

What does Th2 secrete? what does it stimulate?

A
  • Secretes IL-4 and IL-5
  • Class switching to IgE
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5
Q

Antibody secreted as a monomer in small quantities?

A

IgE

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6
Q

Function of IgE?

A
  • Binds cells with Fc receptor = triggers granulation of granulocytes
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7
Q

Antibody predominantly found as a dimer secreted in the GI and respiratory tract mucous?

A

IgA

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8
Q

Functions of IgA? (2)

A
  • Neutralizing and aggregating pathogens
  • Developing tolerance within mucosal immune system
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9
Q

Antibody produced in highest quantities in our body?

A

IgA

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10
Q

ILCs that are cytotoxic monitors of
and responders to abnormal-looking or stressed cells?

A

NK Cells

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11
Q

Where are resident ILCs found?

A

Barrier tissues

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12
Q

ILCs that secrete cytokines such as IFN-gamma and TNF-alpha?

A

ILC1

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13
Q

ILCs that secrete cytokines such as IL-4, IL-5, IL-9, IL-13?

A

ILC2

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14
Q

ILCs that secrete IL-17 and IFN-gamma?

A

ILC3

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15
Q

What are type 3 ILCs effective against?

A

Extracellular bacteria

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16
Q

Trans-membrane proteins that can act as channels for small molecules (paracellular)

A

Claudins

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17
Q

Trans-membrane protein, function not clear

A

Occludin

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18
Q

Trans-membrane protein that may mediate permeability to larger molecules

A

Junctional Adhesion Molecules (JAMs)

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19
Q

Protein important in tight junction formation, interact with the cytoskeleton

A

ZO-proteins

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20
Q

Large collections of lymphoid nodules in the ileum?

A

Peyer’s patches

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21
Q

What is the luminal surface of a Peyer’s patch lined with?

A

M (microfold) cells

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22
Q

MALT nodules without capsules found throughout the gut?

A

Isolated lymphoid follicles (ILFs)

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23
Q

Gut cells with immune function? (4)

A
  • Enterocytes
  • Goblet cells
  • Paneth cells
  • Microfold cells
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24
Q

Where are PRRs generally on enterocytes?

A

Tend to be intracellular or
located at the basolateral surface (come on luminal surface)

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25
Q

How do enterocytes translocate IgA? (3)

A
  1. enterocyte grabs IgA from plasma cells in LP
  2. Assemble with secretory component and J-chain
  3. Exocytosis
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26
Q

What is the e receptor that binds to secreted IgA at the basolateral surface of the enterocyte?

A

Polymeric IgA receptor

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27
Q

Cells found all throughout the intestine, but the highest population in the colon?

A

Goblet cells

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28
Q

Function of goblet cells? (3)

A
  • Secrete mucous = barrier to invasion
  • Secrete anti-microbial peptides (AMPs)
  • Can transport antigen from lumen to APCs in LP
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29
Q

What cells are located in the crypts that secrete large quantities of AMPs?

A

Paneth cells

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30
Q

Very specialized cells present over the surface of Peyer patches and isolated lymphoid follicles (ILFs)?

A

Microfold cells (M cells)

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31
Q

Apical surface of M cell?

A

Smooth = captures antigen

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32
Q

What part of M cells intimately contacts PACs and lymphocytes?

A

Large basolateral “pocket”

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33
Q

Is more or less mucous found over sites with M-cells?

A

Less

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34
Q

What is the M cell basement membrane like?

A

Sieve

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35
Q

The GI tract must? (2)

A
  • maintain commensal bacteria and be exposed to potentially antigenic macros
  • fight off pathogenic molecules
36
Q

The GI tract must not?

A

Develop an inflammatory response to potentially antigenic macronutrients or healthy commensals

37
Q

Mucous in the lumen impairs bacterial ________ and makes it difficult for bacteria to penetrate the __________

A

mobility; epithelial barrier

38
Q

What in the mucous of the lumen impairs bacterial mobiity?

A

Mucins and glycoproteins

39
Q

What layer is very thick in the large intestine? What does it contain a lot of?

A
  • Mucous layer
  • Goblet cells
40
Q

What can degrade bacterial cell walls or create pores in them? (3)

A
  • Defensins
  • Phospholipases
  • Lysozymes
41
Q

Secreted mostly by Paneth cells, mainly toxic against gram (+)-ve bacteria but also seems to have some activity
against gram (-)-ves?

A

REG3 - unique to GI tract

42
Q

What is “unshuffled” IgA?

A

The antibody sequence has not undergone affinity maturation - broadly specific for wide range of microbes

43
Q

What do unshuffled IgA generally inhibit?

A

Microbe penetration into mucosa

44
Q

What does it mean for unshuffled IgA to be somewhat tolerogenic?

A

Reduces the likelihood of inflammation in the mucosa

45
Q

What is shuffled high-affinity IgA?

A

The antibody sequence has undergone affinity maturation due to Th-B cell interactions

46
Q

Why are shuffled IgA more deadly?

A

They have higher affinity for pathogens that have been recognized as pathogenic

47
Q

Are shuffled or unshuffled IgA more likely to be related to overall gut inflammation?

A

Shuffled

48
Q

4 methods for bringing antigen from lumen to APC?

A
  1. M cell dependent
  2. FcR dependent
  3. Goblet cell dependent
  4. Direct APC contact
49
Q

Methods of antigen presentation may be tolerogenic or cause the development of inflammation and this depends on what?

A

The activation state of APC and presence of messengers

50
Q

If a microbe penetrates the epithelial barrier, what response is likely?

A

Pro-inflammatory response

51
Q

Tolerogenic features and molecules in a non-inflammatory gut environment? (3)

A
  • Low/No molecules that promote type 1 or 2 inflammation
  • Low levels of signals associated with Th17 and ILC3 activation
  • normal levels of anti-inflam cytokines and Th cells
52
Q

Signals associated with maintenance of tolerance in the gut? (3)

A
  • IL-10, retinoic acid, TGF-beta
  • APRIL, BAFF
  • Low levels of Th-17 cytokines
53
Q

What do IL-10, retinoic acid, TGF-beta do? (2)

A
  • Enhance Treg and IgA production
  • inhibit inflammation
54
Q

What do APRIL and BAFF do? (2)

A
  • Pro-B cell messengers
  • Enhance T-independent B cell production of IgA
55
Q

What are Th17-type cytokines and what do they do?

A
  • IL-23, IL-17, IL-22
  • Enhance production of anti-microbial proteins
56
Q

IgA is secreted from plasma cells from what 3 major sources?

A
  1. ILFs
  2. Peyer’s patches
  3. Plasma cells in mesenteric lymph nodes around abdominal aorta
57
Q

Most of the IgA secreted in the lumen is from what 2 sources?

A

ILFs and Peyer’s patches

58
Q

T-dependent IgA class switching?

A

Tfh induce IgA class switching in B cells via TGF-beta and CD40L/iCOS interactions

59
Q

What is the result of T-dependent IgA class switching?

A

The production of ONE or A FEW specific antibodies

60
Q

T-independent IgA class switching?

A

BAFF and APRIL are secreted by the mucosal dendritic cells and enterocytes

61
Q

What are the results of T-independent IgA class switching? (2)

A
  • Low affinity Ab’s quickly produced
  • MANY different types of Ab’s produced
62
Q

Where is T-independent IgA class switching likely to take place?

A

Much more likely to be produced in a tolerogenic environment

63
Q

There are quite a few _____ and _____ cells in a healthy gut, and less _______ or _______

A

ILC3 and Th17; ILC2/ILC1 or TH1/Th2 cells

64
Q

Human ILC3 cells seem to respond to…? (2)

A
  • Directly to microbes via TLRs
  • To RA and IL-23 released from innate immune cells and enterocytes
65
Q

What do ILC cells do when activated? (3)

A
  • Secrete IL-22 and IL-17 = produce AMPs by enterocytes and Paneth cells
  • Secrete factors that induce Peyer’s patch, ILF, and IgA production
  • Amplify Th17 response in gut
66
Q

How does Th17 response facilitate IgA production? (2)

A

Can be induced and become either:
- Tfh = Ab production in follicles and lymph nodes
- Treg = anti-inflam cytokine prod = down regulate APCs

67
Q

Does SI or LI have larger microbial community?

A

Large Intestine

68
Q

What are there more of in the SI?

A
  • Paneth cells
  • M cells
  • Peyer’s patches
69
Q

What are there more of in the LI?

A
  • Goblet cells
  • ILFs
70
Q

Commensal microbiome tends to…? (2)

A
  • Stimulate development and accumulation of Tregs
  • Aid in development of MALT
71
Q

3 major commensals in the SI?

A
  • Firmicutes
  • Actinobacteria
  • Bacteroidetes
72
Q

Development and accumulation og Tregs can be through the secretion of what?

A

Short Chain Fatty acids (SCFAs)

73
Q

How can commensals aid in the development of MALT?

A

ILC3 can detect commensals through TLR signalling

74
Q

What bacterial family by themselves enhance IgA production and Th17 development?

A

Firmicutes

75
Q

What is the degradation product that is resistant to proteolytic degradation by pancreatic enzymes in celiac disease?

A

Alpha-gliadin

76
Q

What chemokine receptor does gliadin being to and what is the result?

A

CXCR3 = produces and releases zonulin extracellularly

77
Q

What does zonulin do?

A

Binds to its receptor, disassembles ZO proteins = disassembles TJs

78
Q

What does gliadin cause to be produces by enterocytes and what does it do?

A

IL-15 = causes intra-epithelial lymphocytes to express NK cells activating receptors

79
Q

APCs phagocytose gliadin and some individuals will express _____ that present gliadin in a way that activates Th1 or Th17

A

HLA2

80
Q

HLA-DQ2 or HLA-DQ8 are necessary for what?

A

Perpetuate inflammation and destruction of villi

81
Q

What does destruction of intra-epithelial lymphocytes, TJ integrity, and ongoing inflammation lead to? (3)

A
  • Development of self-antibodies (tissue-transglutaminase Ab’s)
  • Destruction of villi
  • Migration of immune cells into crypts and lamina propria
82
Q

Adult presentation of celiac disease (5)

A
  • Anemia
  • Chronic diarrhea
  • Bloating
  • Fatigue
  • Deficiencies in B12 and iron
83
Q

Pediatric presentation of celiac disease (5)

A
  • Irritability
  • Anorexia
  • Chronic diarrhea
  • Weight loss/malabsorption
  • Some with abdominal pain, nausea, vomiting, bloating, constipation
84
Q

Extra-intestinal manifestations of celiac disease all ages (4)

A
  • Joint pain/arthritis
  • Aphthous somatitis
  • Iron deficiency anemia
  • Dermatitis herpetiformis
85
Q

Extra-intestinal manifestations of celiac disease in children (2)

A
  • seizure disorders
  • pubertal delay and short stature
86
Q

Gold standard diagnostic test for celiac disease?

A

Duodenal biopsy

87
Q

What antibodies have a >95% specificity and sensitivity for celiac disease diagnosis?

A

Anti-tissue transglutaminase Ab’s