Balance + Regulation of GIT - Immunology Flashcards
Recap, what mucosal immunity do we have?
- Mucosal immune system must be able to recognise and eliminate pathogens in the presence of non-pathogenic microbes
What 3 layers of the mucosal surface do we have to try and limit inflammation?
How does surveillance ensure an anti-inflammatory response? (4 structures)
What are the 4 ways the mucosal immune system samples?
- Dendritic cells and macrophages in the gut have evolved a phenotype which allows phagocytosis but not inflammatory cytokine secretion.
> In resting conditions the epithelium produces anti inflammatory cytokines
Compare the differences in response for:
1- When sampled microbiota cause an anti-inflammatory defensive response
2- Bacteria enter through other means an inflammatory reaction occurs
1- What are the 4 main functions of commensal bacteria?
2- What does bacteria in the colon do? What are the implications of this?
5- The bacteria in the colon ferment non-digestible carbohydrates into short chain fatty acids – acetate, propionate & butyrate
> High levels of SCFAs = lower risk diet obesity and insulin resistance and are absorbed and reach the liver and peripheral organs used for gluconeogenesis and lipogenesis
What common microbiota do we have?
The ratio of bacteria to human cells in men and women is?
- 4:3 in men and 11:5 in women
> Symbiotic and mutualistic relationship between the commensal bacteria and humans
1- How are we first colonized by microbiota?
2- What factors affect the colonisation of microbiota after birth?
3- What age do we acquire adult-like microbiota?
1- Foetus is exposed to microbes in the uterus.
2- Mode of delivery, diet, hygiene and antibiotic exposure
3- By 3 years of age you have acquired an adult- like microbiota and established symbiosis
What microbiota is found in breast milk? What is its function?
- Bifidobacterium longum is present in breast milk and can break down oligosaccharides in the breast milk, also produces lactic acid to reduce pathogenic colonisation
What are the differences between the mucosal immune systems of germ-free mice and those with commensal bacteria?
- This shows that commensal bacteria are involved with the development of the mucosal immune system.
What experiment with mice showed that Gut microbiota affects weight?
- Mice kept germ free have no microbiota
- When given microbiota from an obese mouse they show a significant weight gain
- Ob/Ob microbiota had high abundance of Firmicutes
what experiment showed that Bacteroidetes are sensitive to calorie intake?
- Humans patients:
> When put on a low fat or low carbohydrate diet Bacteroidetes levels increased proportionally and correlated with a reduction in body weight
= Suggests that Bacteroidetes are sensitive to calorie intake and changes result in an improved metabolic phenotype
How does an imbalance of microbiota allow for opportunistic infections? Give an example.
- Dysbiosis
What is focal microbiota transplantation?
- Donor stool usually a close relative is screened for infectious diseases and produced into a bowel prep for patients
> Infused into recipient through NG tube, enema or colonoscope
(if donor obese likely to become obese)
- Describe how a diet of Dietary fibre, pre biotics and pro biotics ensures good health.
- Describe how a diet of saturated fat intake, high sugar, PPIs, Excessive protein and altered PH can cause disease?
Compare Ulcerative colitis to Crohn’s disease?
Compare the symptoms of Ulcerative colitis to Crohn’s disease.
Why do we develop inflammatory bowel disease?
- Gut microbiota may trigger changes
-
Excessive activation of the GI immune system towards the intestinal bacteria
> Having T cells that recognise certain commensal bacteria which are potentially driven by IL-12 and a lack of IL-10 can cause IBD
Crohn’s disease is an immune response to our own commensal bacteria, there is a strong genetic component with familial clustering.
- What 5 genes are involved with Crohn’s,What is there role normally and how do they do to contribute to Crohn’s disease?
- An unknown environmental trigger initiates the inflammation, when established the immune system starts an inflammatory feedback loop
What inflammatory cytokine has significant function is Crohn’s?
- TNFα has a significant function as it’s signalling cascade is linked with IL-1β & IL-6. IL-17 mRNA is upregulated in the mucosa
Describe the immunological process of Crohn’s disease.
What is the aim for the treatment of Crohn’s?
- What 3 main types of treatment can we use for Crohn’s?
Focuses on reducing inflammation to relieve symptoms and trigger remission
How does the immune system detect the difference between pathogenic and non pathogenic molecules?
- Oral tolerance
1- Soluble proteins and macromolecules are taken up through M cells
2- Entered via the oral route no antibodies have previously been produced
3- Dendritic cells present the antigen alongside IL-10 which results in no innate immune activation. Teaching the immune system that this not a pathogenic molecule.
4- High doses of antigen presented by dendritic cells can also stimulate anergy in effector T cells
= oral tolerance to these proteins
What is Coeliac disease? What are the symptoms?
- Immune mediated inflammatory disease directed towards gluten
- HLA DQ2 or HLA DQ8 allowing their dendritic cells to present the gluten antigen responsible
> Diarrhoea
Malabsorption
Weight loss (predominantly seen in children).
Anaemia
Irritability
Muscular wastage are also often seen
1- How would celiac disease present histologically?
2- What tests/ markers are relevant to coeliac?
- Villous atrophy is a key indicator - loss of the villi and mature epithelium leading to reduced absorption
- Serologic markers are highly sensitive and patients are tested for IgA antibodies to tissue transglutaminase (anti-TTG).
Can also test for anti-gliadin and anti-endomysial
Describe the immunological process of Coeliac disease.
