Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Module 3 > IBD: mechanisms and new treatments > Flashcards

IBD: mechanisms and new treatments Flashcards

1
Q

What are the types of IBD?

A

UC and Crohns; Behcets; vasculitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the important differential diagnosis in UC?

A

amoebic colitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the important differential diagnosis in Crohn’s?

A

yersinia and TB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How many genetic loci have been identified to be associated with IBD?

A

163

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How many of the genetic loci associated with IBD in general are shared between CD and UC?

A

110

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What other diseases share the 110 IBD loci associated with both CD and UC?

A

common pathways in leprosy; mycobacterial susceptibility; lots of other immune mediated diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the important genes implicated in CD risk?

A

NOD2 and PTPN22

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the important gene implicated in UC?

A

MHC- chromosome 6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What makes gut immology a difficult balance?

A

the gut is constantly bombarded with foreign antigens- some such as food and commensals we want no response- tolerance whereas we do want immune activation to pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is seen in the gut inflamamtory state?

A

exists in a state of controlled or physiological inflammation- lymphocytes in the lamina propria and epithelium is unique and are stimualted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What indicates that there is always some immune activation in the gut?

A

cytokine production levels are high even in physiological states- especially IFNy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What controls the state of inflamamtion in the gut?

A

immune suppression and effective barrier function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What in the gut protects against GI pathogens?

A

saliva; stomach acid and enzymes; bile; water and electryolye secretion/persitalsis; epithelial barrier; bacterial flora

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the realtionships between the gut microbiota and the host?

A

symbiotic relationship; immunologically distinct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give an exmaple of how the gut flora prevent colonisation by pathogens?

A

if give antibiotics and get rid of commensal bacteria, C.diff gains a foothold and produces toxins that cause mucosal injury and the leakge of nuetrophils and RBCs into the gut between injured eptihelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens when there is breakdown of the epithelial barrier?

A

dominant N-cadherin negative chimeric mice had patchy disruption of E-cadherin expression leading to focal increases in intestinal permeability-chornic focal intestinal inflammation even with normal immune system –Hermiston and Gordon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What suggests that IBD is not solely a problem with the adaptive immune system as suggested by biopsy with massive lymphocyte infiltration?

A

NOD2 and CARD15 are innate mechanisms implicated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the different types of GALT?

A

tonsils; adenoids; peyers patches; appendix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the function of M cells?

A

interspersed between enterocytes and in close contact with lymphocytes and DCs; they take up antigen from the gut lumen by endocytosis and release to APCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How are gut immune repsonses iniated?

A

M cells provide antigen to APCs which then migrate to mesenteric lymphoid tissue where they activate T cells who then move back to mucosa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How may intestinal epithelial cells be involved in the immune repsonse?

A

act as non-professional APCs; present antigens to and stimulate lymphocytes using the non-classical pathways of stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Where are lamina propria lymphocytes found?

A

under the epithelium in the stroma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Where are intraepithelial lymphocytes found?

A

between intestinal epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What type of T cell are intraepithelial lymphocytes?

A

many are TCRyd

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What do the intraepithelial lymhocytes produce?

A

IL-2 and IFNY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What type of lymphocyte are the lamina propria lymphocytes mainly?

A

CD4- Th1; Th2 and Th3/Tr1- regulatory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What suggests that Crohns disease may be a Th1 mediated disease?

A

granulomata are seen-cellular immunity; CD patietns have increased mucosal levels of IL-6; IL8- IL-12; IFNy and TNFa; may regress in AIDs; antibodies that block Th1 cytokiens improve CD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Why may UC be a Th2 disease?

A

increased levels of IgG1; elevated IL-5 BUT lots of Th1 cytokiens as well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What cytokine stimulates Th2 differentiation?

A

IL-4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the transcription factors of Th2 cells?

A

GATA-3; STAT-6

31
Q

What stimulates Th1 differentiation?

A

IL-12

32
Q

What stimualtes Th17 differenation?

A

TGF-b; IL-23; IL-6

33
Q

What are the transcription factors for Th1 cells?

A

T-bet; STAT4

34
Q

What is the trascnription factor for Th17?

A

STAT-3

35
Q

What suggests that Crohns and UC are Th17 mediated diseases?

A

mouse model IL-23 is essential for inflammation; both Th1 and Th17 cells can be found in CD- Annunziato; IL-23 if necessary for chronic inflammation in the IL-10 KO but IL-12 isn’t -Yen; IL-23R polymorphisms are associated iwth CD and UC- Duerr

36
Q

What is the relative risk of homozygot for mutations in NOD2 for ileal disease?

A

30.3 -Ahmad

37
Q

What is the function of NOD2?

A

intracellular receptor for muramyl dipeptide of bacterial cell wall

38
Q

What domain does muramyl dipeptide of bacterial cell wall bind to on NOD2?

A

LRR

39
Q

What happens when the LRR of NOD2 is activated?

A

CARD15 is activated

40
Q

What are hte possible reasons for why NOD2 increases CD risk?

A

defective NOD2 resutls in defective Caspase 9 mediated apoptosis induced by CARD15; or in Paneth cells results in redued antimicrobial peptides and uncontrolled microbiota

41
Q

What are the genes associated with Crohns disease?

A

MHC- esp. MHC-II; CARD15- Ahmad; IL-23R polymorphisms- Duerr; TCR polymorphisms;

42
Q

How may CARD15 interact with Th17 cells in CD?

A

MDP stimualtes IL-17 production by DCs via CARD15 which is lost in CARD15 deficiency- not sure what the digniscance

43
Q

What is the first line therapy for mild to mod UC?

A

aminosalicylates

44
Q

When is nutritional therapy in Corhns typically used?

A

in children- to avoid harmful immunsuppression

45
Q

Give an example of an immunomodulator in IBD?

A

azathioprine

46
Q

Why are biologics needed in IBD?

A

steroids have a lot of SEs, don’t result in mucosal healing; immunosuppressives have SEs; slow onset

47
Q

What are the possible biologic targets in IBD?

A

prevent the initial triggering of inflammation by gut microbiota; prevent migration and adhesion of inflam cells; prevent activation of T cells; upregulation of immunoregulatory cells/ cytokines

48
Q

Why does vedolizumab- ant-integrin take 10-12 weeks to work?

A

prevents further migration; length of time reflects life span of cells already in the gut

49
Q

What are hte concerns about anti-TNF treatment?

A

malignancy- reduced immune surveillance; bad in heart failure?

50
Q

What is the mechanism of ustekinemab?

A

targets the common subunity of IL-12 and IL-23

51
Q

Whati s the efficacy of infilximab in IBD?

A

remarkable mucosal healing after 6 weeks

52
Q

What is the best marker of clinical benefit in IBD?

A

mucosal healing

53
Q

What is the common subunit of IL12 and IL23?

A

p40

54
Q

What is ustekinemab currently licensed for?

A

psoriasis

55
Q

When is ustekinemab used?

A

anti-TNF resistant CD - increased clinical remission and clinical repsonse

56
Q

What does vedolizumab target?

A

a4b7 integrin and inhibits lymphocyte tracking to the gut

57
Q

What is the function of tofacitinib?

A

blocks phosphorylation of STAT by Jak and downstream activation

58
Q

What are hte different biologics being trailled in IBD?

A

anti-TNF: inflixumab; anti-integrins- vedolizumab; anti-12/23- ustekinemab; tofacitinib

59
Q

What has been the effect of tofacitinib ?

A

improved clinical response; remission; endoscopic response-Sandborn

60
Q

What is hte function of SMAD7?

A

downregulated the phosphorylation of SMAD3, which mediates TGFb related immune regulation

61
Q

What was the in vitro efficacy of SMAD7 inhibitor?

A

reduced SMAD7 and increased phosphorylation of SMAD3 restoring TGFb signalling and reducing expression of IL1 and TNFa

62
Q

What does the effect of sekukinumab on CD suggest about the role IL-17 in the gut?

A

anti-IL-17 made CD worse usggesting some underlying IL-17 is needed for gut integrity?

63
Q

What are the mechanisms of CD and UC?

A

genetic susceptibility and environmental triggers which cause unregualted activation of hte immune response and inflammation with both the innate and adaptive immune reponses implicated

64
Q

What is inflammatory bowel disease?

A

chronic inflammatory state of the GI tract that is classified in 2 main clinical phenomena- CD and UC

65
Q

What suggests taht Th17 is implicated in IBD?

A

STAT3 and IL-17 are increased in inflamed colon tissue; massive infiltration of th17 cells in their mucosa; GWAS studies implicate Th17 pathways

66
Q

What is the effect of IL-18 in Crohns disease?

A

increased in the mucosa of CD patietns and increases the Th1 response whilst reducing IL-10 release from T cells

67
Q

What is the effect of IL-33 in UC?

A

stimualtes mucus secretion to protect the epithelium and upregulates IL-5 and IL-13 as part of hte Th2 repsonse- upregulated in UC

68
Q

How does TNFa relate to IBD?

A

clinical severity is correlated with serum TNFa levels; increases expressiong of IL-1b; IL6 and IL-33

69
Q

What relates Th17, gut microbiota and IBD?

A

biopsy samples have shown that changes in the composition of hte microbiota may be associated with IBD pathogenesis; the process of Th17 cells, implicated in IBD progression is impacted by microbiota- segmented filamentous bacteria induce Th17 cells; and Th17 differentation is decreased in germ free system and in antibortiocs

70
Q

How can IL-17 be used as a marker of clinical severity?

A

expression in PMBCs of IL-17 corrrelates with UC severity

71
Q

What suggests that importance of Tregs in IBD?

A

mutations in CD25 and IL-10 lead to increased susceptibility to IBD; ablation of Treg cells increases colitis expression

72
Q

How could Tregs be used therapeutically?

A

in a Rag1 KO mouse model, transfer of Tregs decreased intestinal inflammation

73
Q

What are new avenues of research in IBD?

A

specific mixtures of macronutrients and emulsifiers within the diet affect intestinal permeability, gut microbiota desnity and predispose to intestinal inflam; allogeneic expadned adipose-derived stem cells result in long-term clinical and radiological healing in treatment-refractory perianal Crohns

Module 3 (33 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions