IBS

Question 1

what is IBS

Answer 1

Ibs is a chronic inflammatory disease of the gastrointestinal tract that encompasses crohn’s disease and ulcerative collitis. prevelance in industrialised countries and symptoms include diaerhoea, rectal bleeding and abdominal pain. its an abnormal immune response against microorganisms in the intestinal flora

Question 2

Role of innate immune system in IBS

Answer 2

There are defects in the permeability of the epithelial barrier of the intestine. Bacteria in the git trigger epithelial cells to secrete bactericidal agents via activation of prr il-23 promotes differentiation of t heler cells to th 17

Question 3

Role of adaptive immunity

Answer 3

T-helper cells of the th-17 type are upregulated in both crohn’s disease and ulcerative collitis

Th1 cells stimulate release of Interferon-γ, which directly attacks enterocytes and acts on macrophages to release TNF-α, which stimulates release of matrix metalloproteinases (MMPs), which degrade tissue and digest the basement
membrane of enterocytes

Question 4

Treatment for IBS

Answer 4

includes local antiinflammatory agents (corticosteroids and salicylates)
– Salicylates include sulfasalazine, mesalazine, balsalazide and olsalazine

First-line immunomodulatory drugs include corticosteroids, azathioprine and
methotrexate.

Question 5

Calcineurin inhibitors MOA cyclosporin

Answer 5

cyclosporin - isolated from fungi , which binds to cyclophilin a (cytoplasmic protein) the complex then inhibits calcineurin
Calcineurin inhibition results in reduced NFAT (Nuclear Factor of Activated T Cells) induced transcription of interleukin-2 and then subsequent inhibition of
T-Cell activation

Question 6

calcinurin inhibitor

Answer 6

Tacrolimus and pimecrolimus binds to FK506 binding protein 12 which inhibits calcinuerin

CI’s are most effective immunosuppressive drugs, they are also used to prevent rejection in solid organ transplantation, psoriasis and eczema . Both cyclosporin and tacrolimus are substrates of cyp3a4 .

Question 7

Integrin inhibitors

Answer 7

integrins are cell surface proteins expressed on circulating leukocytes. cell adhesion molecules are expressed on endothelial cells. they work together to recruit leukocytes to site of inflammation. inhibitors are referred to as anti-adhesion or leukocyte -trafficking inhibitors

Question 8

Examples of integrin inhibitors

Answer 8

Natalizumab - a mab against the a4b7 and a4b1 integrins on
Vedolizumab - a mab against a4B7-integrin
Etrolizumab - a mab that targets a4b7 and aeb7
Natalizumab increases risk of CNS infection

Question 9

Examples of integrin inhibitors

Answer 9

Natalizumab - a mab against the a4b7 and a4b1 integrins on
Vedolizumab - a mab against a4B7-integrin
Etrolizumab - a mab that targets a4b7 and aeb7
Natalizumab increases risk of CNS infection

Question 10

IL-12 and 1l-23 antagonists

Answer 10

Ustekinumab is a mab against a subunit called p40 of both IL-12 and IL-23 and is useful in crohn’s disease.