10- Immunology Flashcards
Describe the number of microbiota at different points in the gi tract
Loads in the mouth is because we put lots of dirty things into it, including food, fluid, cutlery, air etc.
Into the stomach, the low pH kills lots of bacterial populations (except H. pylori).
The number is kept low in the duodenum, jejunum and proximal ileum because of paneth cells and Peyer’s patches (discussed in detail later).
Beyond the ileocaecal valve the number of microorganisms increases markedly.
4 mechanisms of mucosal defence
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.
What are peyers patches
Peyer’s patches consists of aggregated lymphoid follicles covered with follicle associated epithelium (FAE).
found in the small intestine - highest concentration in the distal ileum.
they monitoring local bacteria, and provide protection against pathogenic bacteria.
Their development requires exposure to bacterial flora
Humans have about 50 by the last trimester of gestation, and hit the maximum of about 250 by their teenage years.
Peyer’s patches are rich in B cells, T cells, macrophages and dendritic cells.
What are m cells
FAE contains specialized enterocytes or M cells. 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.
Antigen uptake is a combined effort by specialised M-cells and dendritic cells. These antigens are then presented to the lymphocytes for assessment and potential immunological response. Activated cells develop gut homing markers and migrate to mesenteric lymph nodes for proliferation.
How is secretory IGA produced and what does it do
SIgA is a dimeric form of IgA produced by B cells in the lamina propria and transported across the enterocyte. In the plasma cell, two IgA molecules are bound together by a J-chain, and secreted into the interstitial space. The dimer binds to a special receptor on the external basolateral surface of enterocytes (polymeric immunoglobulin receptor; pIgR). This receptor becomes the secretory component and binds to the length of the IgA dimer, becoming SIgA. 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. 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.
SIgA binds to pathogens, preventing their adherence to the mucosal wall.
What happens when galt lymphocytes are activated
Mucosal lymphocytes in Peyer’s patches, once stimulated by an antigen, migrate into the local mesenteric lymph nodes and drain into the lymphatic system.
They reach the systemic circulation via the thoracic duct and spread throughout the body in the blood. These lymphocytes remain in the blood until activated by tissue-sepecific endothelial adhesion molecules at the site of inflammation, which permit transmigration of the lymphocytes into the gut mucosa.
This is called lymphocyte homing and requires specialised post-capillary microvascular endothelial cells, such as the high endothelial venules (HEVs) of lymphoid tissue.
How do the lymphocytes enter the gut through HEVs
In HEVs, L-selectin mediates lymphocyte rolling by its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1).
In addition to the 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.
3 symptoms of IBS
Recurrent abdominal pain
Abnormal bowel motility
Constipation and/or diarrhea
4 methods of treating IBS
Diet modification - Avoiding certain foods such as apples, beans, cauliflowers.
Treatment of constipation - soluble fiber, stool softeners and osmotic laxatives
Treatment of spasms and pain - anti-diarrheals, anti-muscarinic
Management of stress, anxiety, depression
3 symptoms of coeliac disease
Abdominal distension (bloating)
Diarrhoea
Sometimes dermititis herpetiformis
Mechanism of coeliac disease
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.
Symptoms of crohn’s
Pain in affected area, most commonly in right lower quadrant.
Diarrhea and blood in stool.
Mechanism of crohns
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.
How can crohns be treated
Use of medications such as anti-inflammatory drugs and antibiotics.
For severe symptoms, immunosuppressants such as corticosteroids can be prescribed.
Surgical removal of affected tissue, but it does not cures the disease.
Crohn’s: liquid diet, low fibre/low residue, food reintroduction
2 Symptoms of UC
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).
