GI mucosal immunology treatment Flashcards

1
Q

what role does the colonic mucosa play in physiological immunity?

A

it detects luminal contents and recognises commensal bacteria from pathogens that require a robust immune response

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2
Q

What do we want our immune system to do? (3)

A

develop self tolerance - recognise self antigens as non-threat

develop exogenous tolerance - not reacting to the vast array of newly encountered environmental antigens - food and microbes

develop an effective immune response - eliminate or control infections, allergic and noxious agents

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3
Q

How does the epithelial layer in the gut help with immunity

A

single cell thick – tightly packed – tight control of permeability - prevents microbes getting through

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4
Q

What are the 2 antigen presenting cells

A

dendritic cells and macrophages

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5
Q

What are the soluble mediators of immunity called? what do they do

A

chemokines
cytokines

soluble mediators of the immune response - control functional cells and migration of cells to area if immune response is required

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6
Q

Adaptive immunity: cell types

A
CD4+ T cell 
CD8+ T cell 
B cell
(memory cells) 
plasma cell
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7
Q

Innate immunity: cell type

A
granulocyte
mast cell
monocyte
dendritic cell
macrophage
natural killer cell
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8
Q

What type of responses can cytokines provoke?

A

Pro inflammatory and anti inflammatory response

most cytokines have a specific response but some can be both

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9
Q

What does it mean to maintain immune homeostasis?

A

can have a proinflammatory or anti-inflammatory/regulatory (which dampens down inflammation) - need to have a balance of these responses to maintain gut health

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10
Q

What are peyer’s patches?

A

small masses of lymphatic tissue found in the small intestine - they lie underneath the epithelial barrier - have special cells called M cells that transport antigens from the lumen to cells of the immune system, thereby initiating an immune response or tolerance - antigen presentation

important role in tolerance and active immunity

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11
Q

what is the 1st line defence system in the gut?

A

Macrophages

phagocytosis of foreign microorganisms

they secrete cytokines - pro and anti inflammatory

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12
Q

what role do dendritic cells play in immunity?

A

important for mucosal immune responses - they direct the function of T cells

they present antigen to naive T cell - one that hasn’t decided which subset it is yet

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13
Q

where are dendritic cells found?

A

lamina propria and peyer’s patches

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14
Q

what do dendritic cells become when they undergo maturation?

A

Potent antigen presenting cells

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15
Q

What 3 signals are involved in the interaction between dendritic cells and T cells

A

MHC/peptide-TCR
CD80-CD28
Cytokine

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16
Q

name 3 T regulatory cells

A

Th3
Tr1
Treg

17
Q

What can happen when normal immune homeostasis goes wrong?

A

Inflammatory bowel disease (IBD)

Coeliac disease

18
Q

what is dysbosis

A

microbial imbalance

- damaged epithelial barrier, increased bacterial adherence and translocation (leaky gut) - chronic inflammation

19
Q

Pathogenesis of IBD

A

barrier defect
increased mucus
microbial dysbosis

20
Q

what is NOD2

A

a protein that senses bacteria that has managed to pass through the epithelial cell

21
Q

treatment strategies for IBD (5)

A

Target lymphocytes directly

Target single cytokines

Target migration of immune cells to GI mucosa

Target multiple cytokines

Target cytokine intracellular signalling pathways
Modulation of microbiota

22
Q

How does anti-TNF therapy work for IBD? what are the mechanisms?

A

works to reduce inflammation

they neutralise the cytokine - cell doesn’t get the signal and doesn’t work as they should normally

cause cell death or apoptosis

23
Q

what are some bad side effects of anti-TNF drugs

A

More susceptible to infection
increased risk of malignancy
toxic effect on nerves

24
Q

what happens if a patient doesn’t respond to TNF

A

use vedolizumab instead - blocks integrin on cell surface of lymphocytes (the signal that tells cells where they are going)

25
Q

Tofacitinib drug

A

blocks JAK pathway - no matter if the cytokine binds - proinflammatory signal can’t get through

there isn’t just one JAK pathway - there are many

26
Q

Faecal microbiota transplant/ stool transplant

A

stool from healthy patient put into diseased patient - to encourage positive microflora to thrive – usually administered using colonoscopy

27
Q

what is coeliac disease

A

inflammatory disorder of the small bowel

intolerance to dietary gluten in wheat and similar proteins

can cause:- Malabsorption – failure to thrive as a child; iron deficiency anaemia, fatigue, GI symptoms – loose stool, abdominal pain or asymptomatic

some people have an inappropriate response to gluten after it has been modified by zonalin

28
Q

Detection of which receptors is a good indication of coeliac disease?

A

HLA-DQ2 and HLA-DQ8