Lecture 26 GI Mucosal Immunology- Treatment of IBD Flashcards

1
Q

What are the facets to normal antigen processing in the colon

A
Epithelial layer
Mucous layer
Innate immune responses
Antigen presenting cells
Adaptive immune response
Soluble mediators of immunity
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2
Q

Innate immune cells

A
Granulocyte
Mast cell
Monocyte
Dendritic cell
Macrophage
NK cell
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3
Q

Adaptive Immune Cells

A

CD4 T cell
CD8 T cell
B cell
Plasma cell

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4
Q

What is the cytokine milieu and what is it a key determinant of

A

Environment of the cytokines

T cell differentiation whether it become Th1 or Th2

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5
Q

Name soluble mediators

A

Cytokines and chemokines

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6
Q

How does Peyer’s patches aid immunity

A

M cells can sample antigen

APC present to dendritic cells which drain into lymph and give the antigen to a T cell

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7
Q

What do macrophages secrete

A

Cytokines

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8
Q

What is the function of dendritic cells

A

Antigen sampling

Present antigen to naive T cells

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9
Q

Where are dendritic cells located

A

Lamina propria

Peyer’s Patches

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10
Q

What maturation do dendritic cells undergo

A

Maturation into potent APC by producing cytokines

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11
Q

The interaction between DC and T cells involves what 3 signals

A
  1. MHC (DC)/Peptide-TCR (T-cell)
  2. CD80 (DC)-CD28 (T-cell_
  3. Cytokine (from dendritic cells)
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12
Q

Name 3 T helper cells

A

Th1, Th2, Th17

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13
Q

Name 3 T regulatory cells

A

Th3, Tr1, Treg

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14
Q

How is the gut health maintained

A

By a balance of T helper cells and T regulatory cells

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15
Q

Pathogenesis of IBD

A

Poor regulation of T cell response

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16
Q

Treatment strategies for IBD

A
  • Target lymphocytes directly- inhibit proliferation and unable exert exaggerated response
  • Target single cytokines- these drive the activation of T cells and IBD TNFs (anti-TNF are antibodies that inhibit pro-inflammatory response)- Adalimumab (less immunogenic)
  • Target migration of immune cells to GI mucosa
  • Target multiple cytokines
  • Target cytokine intracellular signalling pathways
  • Modulation of microbiota
17
Q

Describe multi-cytokine blockade

A
  • Ustekinumab
  • Psoriasis, psoriatic arthropathy
  • Towards p40 subunit of IL-12 and IL-23
18
Q

What is Tofacitinib

A

Multi-cytokine blocking
• Inhibition of IL-2, IL-7, IL-9, IL-12, IL-15, IL-21, IFN, IL-6, IL-12 and IL-23
• Inhibition of JAK pathway (1&3)

19
Q

How can dysbiosis of microbiota be corrected in IBD

A
  • Faecal microbial transplant- restore microbiota

* Used in C. difficile treatment

20
Q

What is Coeliac disease

A

• Intolerance to dietary gluten in wheat & similar proteins

21
Q

What is the genetic susceptibility of coeliacs disease

A

HLA-DQ2/8 on antigen presenting cells

22
Q

What are some features of coeliacs disease

A
  • Loss of villi- loss of absorptive capacity

* Increase in intra-epithelial lymphocytes

23
Q

Name drugs used in Coeliacs disease

A

Larazotide
ALV003
ImmusanTs Nexvax2 vaccine

24
Q

Target of Larazotide

A

Stops gluten fragments from reaching the immune system by preventing the protein zonulin binding to target receptors in enterocytes that instruct the cells to loosen up tight junctions

25
What is the effect of gluten fragments in enterocytes
induce enterocytes to secrete interleukin-15 which stimulates intraepithelial lymphocytes to attack enterocytes
26
Target of Nexvax2 vaccine
exposes the immune system to selected fragments of gluten with the aim of inducing T cells to tolerate, rather than react to gluten • When the modified gluten is presented to helper T cells they are activated, releasing cytokines and chemokines that induce further immune responses