Kura cloud immunology

Question 1

what is the digestive tract part of?

Answer 1

An external environment, because it is possible for bacteria to reach there without needing to cross a membrane.

Question 2

Describe the Distribution of microflora in the alimentary tract?

Answer 2

1. Loads in the mouth is because we put lots of dirty things into it, including food, fluid, cutlery, air etc.
2. Into the stomach, the low pH kills lots of bacterial populations (except H. pylori).
3. The number is kept low in the duodenum, jejunum and proximal ileum because of paneth cells and Peyer’s patches .
4. Beyond the ileocaecal valve the number of microorganisms increases markedly.

Question 3

what are the 4 main mechanism for protection of the GI tract?

Answer 3

Physical barriers: a tight epithelial wall, glycocalyx, mucous and unstirred layer. Also, persitalsis to keep things moving along the GI tract.

Chemical barriers: bacteriacidal enzymes from paneth cells, and acid from stomach.

Bacteria protection: commensal bacteria maintain immune system priming and may attack foreign species.

Immunological: Mucosa-associated lymphoid tissue (MALT) rich in T cells & B cells, whose components can be further categorized into GALT (Gut-associated lymphoid tissue), BALT (Bronchus-associated lymphoid tissue) etc.

Question 4

what can the gut associated lymphoid tissue be split into?

Answer 4

it is split into organised and disorganised sites.

Organised sites:

• sites of lymphoid tissue such as Peyer’s patches in the small intestine
• lymphocytes in mesenteria lymph nodules (i.e. where the lymph from the villi drain).

Disorganised sites:

• lymphocytes in the lamina propria (mainly IgA-secreting B-cells)
• lymphocytes in the interstitial space below the basolateral membrane of the epithelium (called intra-epithelial cells).

Question 5

what does the liver contain that also aids with immunology?

Answer 5

Kuppfer cells in the liver which can phagocytose bacteria.

Question 6

what does peyers patch contain

Answer 6

• Peyer’s patches consists of aggregated lymphoid follicles covered with follicle associated epithelium (FAE)
• Peyer’s patches are rich in B cells, T cells, macrophages and dendritic cells.

Question 7

where is peyers patch most found?

Answer 7

Found in the small intestine, having highest concentration in the distal ileum.

Question 8

What does the development of the peyers patch require?

Answer 8

Their development requires exposure to bacterial flora (i.e. they are barely present in animal models that are born and reared in sterile environments.

Question 9

what specialised cells do Follicle associated epithelium contain?

Answer 9

specialized enterocytes or M cells

Question 10

what is the function of these cells and how do they work ?

Answer 10

The main function of M cells is to perform transcytosis of luminal bacteria, antigens and proteins.
-M cells express IgA receptors, facilitating transfer of IgA-bacteria compex into the peyer’s patches
-

Question 11

how are antigens taken up in peyers patch?

Answer 11

• Antigen is taken up by dendritic cells and M cells
• These antigens are then resented to the lymphocyte for assessment and potential immunological response
• Activated cells develop gut homing markers
• Migrate to mesenteric lymph node for proliferation

Question 12

why is IgA highly prevalent in mucosal secretions?

Answer 12

-MALT is associated with large numbers of IgA+ plasma cells. The number of activated plasma cells reflects the bacterial load and up to 90% gut B cells secrete IgA

Question 13

Describe how IgA is secreted?

Answer 13

-Secretory IgA is a dimeric form of IgA produced by B cells in the lamina propria and transported across the enterocyte

1. In the plasma cell, two IgA molecules are bound together by a J-chain, and secreted into the interstitial space
2. dimer binds to a special receptor on the external basolateral surface of enterocytes (polymeric immunoglobulin receptor; pIgR).
3. This receptor becomes the secretory component and binds to the length of the IgA dimer, becoming SIgA
4. SIgA is then endocytosed into the epithelial cell and actively transported within a vesicle to the apical membrane, where it is exocytosed into the gut lumen

Question 14

what does the secretory component provide for the IgA

Answer 14

The secretory component (on top of its function of helping IgA move through the enterocyte) also protects the antibody dimer from enzymatic and acidic degradation.

Question 15

what is lymphocyte homing?

Answer 15

• Once the antigen has migrated into the local mesenteric lymph node, it drains into the lymphatic system, and reaches the systemic circulation via the thoracic duct and spread throughout the body in the blood
• When lymphocytes are activated by tissue-specific endothelial adhesion molecules at the site of inflammation, it permits transmigration of the lymphocytes into the gut mucosa, this is lymphocyte homing

Question 16

What does lymphocyte homing require

Answer 16

specialised post-capillary microvascular endothelial cells, such as the high endothelial venules (HEVs) of lymphoid tissue.

Question 17

where is mucosal addressin cell adhesion molecule-1 (MAdCAM-1) presented?

Answer 17

HEVs of Peyer’s patches and mesenteric lymph nodes, MAdCAM-1 is constitutively expressed on the flattened endothelial cells localised in the lamina propria of the small and large intestine and enables lymphocyte recruitment in chronic gut inflammation.

Question 18

Describe what happens when the lymphocyte encounters the HEV?

Answer 18

L-selectin, a carbohydrate-binding lectin, is constitutively expressed on the surface of lymphocytes and mediates the low adhesive interactions that enable leukocytes to roll in postcapillary venules and HEVs. In HEVs, L-selectin mediates lymphocyte rolling by its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1)

Question 19

What is irritable bowel syndrome, its symptoms and treatment?

Answer 19

Describes a pattern of recurrent bouts of abdominal pain in abnormal bowel motility – diarrhoea/constipation.
Abdominal pain is often relieved once bowel movement has occurred
Different from IBD which involves the same symptoms but also ulcers/inflammation.
Many have visceral hypersensitivity – means that the sensory nerve endings in the intestinal wall have an abnormally strong response to stimuli. E.g. stretching (during or after a meal)

Features
Short chain carbohydrates such as lactose or fructose, often trigger the symptoms
Diarrhoea if the excess water is not reabsorbed into the body
carbohydrates are metabolised by bacterial flora which produces gas  bloating/spasm/pain
Both stress and gastroenteritis are RISK FACTORS

Treatments
Diet modifications  avoiding foods such as cauliflower, apples – anything with short chain carbs
Constipation medicine  soluble fibre, stool softeners/osmotic laxatives
Spasms and pain  anti-diarrheal, antimuscarinic medication
Manage stress, anxiety, depression

Question 20

what is the mechanism of coelic disease, the mechanism and symptoms?

Answer 20

An immune system mediated disorder where gluten triggers the body’s immune cells to attack self-cells in the small intestine.

An immune system mediated disorder where gluten triggers the body’s immune cells to attack self-cells in the small intestine.
The main problem is gluten specifically a 33 aa peptide called gliadin. Gliadin is very hard to breakdown!
MOST DAMAGE OCCURS IN THE DUODENUM – crypt hyperplasia and villus atrophy

Symptoms:

Abdominal distension (bloating)
Diarrhoea
Sometimes dermititis herpetiformis

Mechanism

Gliadin (33aa peptide component of gluten) is not broken down in the stomach, reaches the small intestine, and binds to the secretory IgA in the mucosal membrane.
Gliadin-secretory IgA complex binds to the Transferrin receptor (TFR) and are transferred to the lamina propria.
Enzyme tissue transglutaminase (tTG) cuts off amide group from the protein.
Deamidated gliadin is phagocytosed by the macrophages, and presented by MHC II molecules.
This leads to activation of immune system causing destruction of epithelial cells.

Diagnosis

Antibody blood tests - anti-gliadin, anti-tTg, anti-endomysial (EMAs)
Biopsy test of duodenum
Dietary management

Gluten-free diet (wheat, barley, rye exclusion) and medication. Can also get gluten-free foods on prescription.
Factors affecting compliance are lifestyle, eating out, cross contamination at home and holidays.

Question 21

what is crohn’s disease?

Answer 21

This is an inflammatory bowel disease that causes inflammation in the bowel – classified as an immune related disorder

ILEUM AND COLON MOST AFFECTED**

Symptoms

Pain in affected area, most commonly in right lower quadrant.
Diarrhea and blood in stool.
Mechanism

Immune-related disorder - triggered by pathogens such as mycobacterium paratuberculosis, pseudomonas, and listeria.
Unregulated immune response causing the destruction of cells in the GI tract.
Gene mutations such as frame-shift mutation in NOD2 gene are thought to be responsible for development of this disease.

Treatment

Immunosupressants
Antibiotics
Diet  liquid diet, low fibre, restriction of diet basically

Question 22

what is ulcerative colitis?

Answer 22

A type of inflammatory bowel disease that specifically refers to inflammation in the colon or the large intestine

Characterised by ulcers in the large intestine and rectum
Most common IBD

Symptoms

Pain in left lower quadrant due to ulcers along the inner surface of large intestine, including the colon and rectum.
Severe and frequent diarrhea (sometimes blood in the stool).

Mechanism

Autoimmune disorder - T cells destroy the cells lining the walls of large intestine
Secondary cause - Diet and stress

Treatment

Anti-inflammatory drugs such as sulfasalazine and mesalamine
For severe cases, Immunosuppressant drugs such as corticosteroids, azathioprine, cyclosporine might be prescribed.
Colectomy - surgical removal of colon cures the disease.
Dietary manipulation to minimise exacerbation of diarrhoea.
Pre/probiotics: to treat and prevent pouchitis (when colon is removed leaving a pouch and becomes inflamed), helps remission of ulcerative colitis. Prebiotics may cause ab- dominal pain, bloating diarrhoea and flatulence
Diarrhoea: drink fluid, nutritious drinks, replace salt. Eating soluble fibre helps the gut absorb more water from stool. Avoid gas producing foods, high fibre or whole- grain cereals, alcohol (worsens dehydration), caffeine and personal triggers.

Question 23

what is cholera?

Answer 23

Symptoms

Vomiting, nausea
Abdominal pain
Severe dehydration and diarrhoea (watery)
Mechanism

Vibrio cholerae is transmitted through fecal-oral route, and spreads through contaminated water and food.
The bacteria reaches the small intestine from the stomach, where the flagellum propels it towards the epithelial cell. On making close contact it releases cholera toxin.
Cholera toxin on entering the epithelial cell, starts a series of biochemical reactions resulting in exit of ions such as Na+, K+, Cl- and water from the epithelial cell.
Diagnosis

Stool test - to detect either the bacteria or the antigen for the bacteria.
Treatment

Drink a lot of fluids.
Depending on the severity of the case, use of IV fluids and/or antibiotics may be prescribed.
Most important precaution is to drink clean water and eat clean food.
Vaccination for cholera is also available.

Question 24

What is the characteristic histological feature of Coeliac Disease?

Answer 24

The main histologic feature of celiac disease is increased intraepithelial lymphocytes