Alimentary immune function Flashcards
Immunology; Immunological disorders
Why is the epithelium of the digestive tract considered an external environment?
It is possible for bacteria to reach there without needing to cross a membrane
What are the gastrointestinal mucosa’s 4 main mechanisms for protection against infection?
Physical barriers e.g. tight epithelial wall, glycocalyx Chemical barriers e.g. bacteriacidal enzymes from paneth cells and stomach acid Bacteria protection e.g. commensal bateria maintains immune system priming and may attack foreign species Immunological e.g.MALT, GALT, BALT
What classifies the two catergories of GALT?
Their organisation
Organised sites such as Peyer’s patches in small intestine and lymphocytes in mesenteria lymph nodules
Disorganised sites such as lymphocytes in the lamina propria and lymphocytes in the intestitial space below the basolateral membrane of the epithelium
What do Peyer’s patches consist of?
Aggregated lymphoid follicles covered with follicle associated epithelium
Rich in B cells, T cells, macrophages and dendritic cells
Where are Peyer’s patches found?
small intestine, largest concentration in the distal ileum
What do Peyers’s patches function as?
“Immune sensors”
They are capable of monitoring local bacteria and they provide protectino against pathogenic bacteria
What does the development of Peyer’s patches require?
Exposure to bacterial flora
Where are M cells found and what are their main function?
Found in follicle associated epithelium
Main function is to perform transcytosis of luminal bacteria, antigens and proteins
What receptors do M cells express and what does this enable?
IgA receptors
Facilitates transfer of IgA-bacteria complexes into the Peyer’s patches
What activates M cells and what happens after they are activated?
M cells and dendritic cells cause antigen uptake
(antigens then presented to lymphocytes for assessment and potential immunological response)
Activated M cells develop gut homing markers and migrate to mesenteric lymph nodes for proliferation
Why is IgA the most abundant antibody in the body?
It is highly prevalent in mucosal secretions because MALT is associated with large numbers of IgA (+) plasma cells
What is SIgA and where is it produced?
Secretory IgA
Dimeric form of IgA produced by B cells in the lamina propria and transported across the enterocyte
How is SIgA produced?
Two IgA molecules are bound by a J chain in the plasma cell, then secreted into the interstitial space
Dimer binds to special receptor on the external basolateral surface of enterocytes (plgR polymeric immunoglobulin receptor)
Receptor becomes the secretory component and binds to the length of the IgA dimer = SIgA
How is SIgA secreted?
SIgA endocytosed into the epithelial cell and actively transported within a vesicle to the apical membrane
Then exocytosed into the gut lumen
What is the function of the secretory component of SIgA?
Protect antibody dimer from enzymatic and acid degradation
helps IgA move through the enterocyte
Binds to pathogens and prevents their adherence to the mucosal wall
What stimulates antigen specific SIgA production?
Actions of M cells and dendritic cells in Peyer’s patches
How are lymphocytes circulated from Peyer’s patches and what is this called?
Once stimulated by antigen, migrate into local mesenteric lymph nodes and drain into the lymphatic system
Reach systemic circulation via thoracic duct and spread throughout body in the blood
Remain in blood until activated by tissue-specific endothelial adhesion molecules at the site of inflammation
This then permits transmigration of lymphocytes into the gut mucosa
CALLED LYMPHOCYTE HOMING
What does lymphocyte homing require?
Specialised post-capillary microvasculature endothelial cells e.g. High endothelial venules of lymphoid tissue
What is L selectin and what does it mediate?
Carbohydrate binding lectin
Expressed on surface of lymphocytes to mediate low adhesion interactions that enabl leukocytes to roll in postacapillary venules and HEVs
How does L selectin mediate lymphocyte rolling in HEVs?
Binds to mucosal addressin cell adhesion molecule-1 (MAdCAM-1)
Where is MAdCAM-1 expressed and what does it enable?
Constitutively expressed on the flattened endothelial cells localised in the lamina propria of the small and large intestine
Enables lymphocyte recruitment in chronic gut inflammation
What are the symptoms of IBS?
Reccurent abdominal pain
Abnormal bowel motility
Constipation and/or diarrhoea
What is the treatment available for IBS?
Diet management - avoiding certain foods
Treatment of constipation - soluble fibre, stool softeners, osmotic laxatives
Treatment of spasms and pain - anti-diarrheals, anti-muscarinic
mangement of stress, anxiety, depression
What are the symptoms of coeliac disease?
Abdominal distension
Diarrhoea
Sometimes dermititis herpetiformis
What is the mechanism of coeliac disease?
Gliadin is not broken down in the stomach, reaches small intestine, binds to SIgA in mucosal membrane
This complex binds to Transferrin receptor and is transferred to the lamina propria
Enzyme tissue transglutaminase cuts off amide group from the protein
Deaminated gliadin is phagocytosed by macrophages and is presented by MHC II molecules
Leads to activation of immune system causing destruction of epithelial cells
How is coeliac disease diagnosed?
Antibody blood tests - anti-gliadin, anti-transglutaminase, anti-endomysial
Biopsy of duodenum
How must diet be managed in coeliac disease?
Gluten free diet
What are the symptoms of Crohn’s disease?
Pain in affected area, most common right lower quadrant
Diarrhoea and blood in stool
What is the mechanism of Crohn’s disease?
Immune-related disorder - triggered by pathogens e.g. mycobacterium paratuberculosis.pseudomonas,listeria
Unregulated immune response causes destruction of cells in GI tract
Gene mutations such as frame shift mutation in NOD2 gene thought to be responsible for development of this disease
What are treatment options available for Crohn’s disease?
Medications such as anti-inflammatory drugs and antibiotics Immunosuppressants for sever symptoms Surgical removal of affected tissue Liquid diet Managing strictures Food intolerance tests for food exclusions Oral nutritional support Diet in remission
What are the symptoms of ulcerative colitis?
Pain in lower left quadrant due to ulcers along inner surface of large intestine, including colon and rectum
Severe and frequent diarrhoea
Sometimes blood in stool
What is the mechanism of ulcerative colitis?
Autoimmune disorder - Tcells destroy cells lining walls of large intestine
Secondary causes can be diet and stress
What is the treatment for ulcerative colitis?
Anti-inflammatory drugs Immunosuppresants for severe cases colectomy to cure disease dietary manipulation to minimise diarrhoea Pre-probiotics
What are the symptoms of cholera?
Vomiting, nausea
Abdominal pain
severe dehyration and watery diarrhoea
What is the mechanism of cholera?
Vibrio cholerae transmitted faeco-orally
Bacteria reaches small intestine and flagellum propells bacteria to epithelial cell where it releases cholera toxin
Toxin enters epithelial cell and starts series of chemical reactions that result in exit of ions and water from epithelial cell
How is cholera diagnosed?
Stool sample test to detect bacteria or antigen for bacteria
What is the treatment for cholera?
Drink lots of fluids Use of IV fluids and/or antibiotics Drink clean water Eat clean food Vaccination available
What is the mechanism of IBS?
not well understood
Visceral hypersensitivity = visceral nerve endings having abnormally strong response to stimuli
