Immunology of the gut Flashcards
What kind of environment is the epithelium of the digestive tract?
External environment because bacteria can reach it without crossing a membrane
What are the 4 mechanisms of defence of GI mucosa?
- Physical barriers
- Chemical barriers (bactericidal enzymes from Paneth cells)
- Bacteria protection
- Immunological
Lymphocytes in the lamina propria do what?
B-cells secreting IgA mainly
What are Peyers patches covered in?
covered in follicle associated epithelium (FAE)
What are Peyers patches rich in?
B cells
T cells
Macrophages
Dendritic cells
Where are M cells found and what is their main function?
Found on FAE.
Main function = perform transcytosis of luminal bacteria/antigens/proteins
M cells express IgA receptors
What does the apical membrane of the M cell have?
Microfold
Why is the basolateral membrane of M cells invaginated?
To reduce intracellular distance that antigens have to travel
How is the apical membrane of the M cell specialised for uptake and transport of antigens?
- Reduced glycocalyx
2. Lack of hydrolytic enzymes
How are large bacteria and particles transported?
By phagocytosis
M cells produce?
IL-1
Cells of the villus side of the crypt develop into?
What about cells in the FAE side of the crypt?
Villus - enteroendocrine cells, enterocytes, goblet cells
FAE side - enterocytes, M cells, rarely goblet cells. Has low number of enterocytes and goblet cells
What lies beneath the FAE?
Sub epithelial dome.
Contains DCs, naive B cells, CD4, CD8, macrophages
Particles transported by M cells can be captured by dendritic cells, which then maturate after migrating to B cell follicles.
Why is an M cell an ideal entry point for pathogens?
Accessibility and ability to transcytose
How is secretory IgA produced?
- Plasma cells secrete IgA dimer bound by a J chain, into interstitial space
- IgA dimer binds to receptor on basolateral membrane of enterocytes.
- Receptor becomes the secretory part of IgA and binds to the dimer. SIgA formed.
- SIgA endocytose and then actively transported to apical membrane.
- Exocytosed into gut lumen.
What does the secretory component of SIgA do?
Helps IgA move through enterocyte. Protects antibody from enzymatic and acidic degradation.
What does SIgA bind to?
Pathogens. Prevents pathogens from being able to adhere to mucosal wall.
Where do stimulated mucosal lymphocytes migrate to?
Local mesenteric lymph nodes. Then reach systemic circulation via thoracic duct.
What is lymphocyte homing, and what does it require?
Lymphocytes in blood get activated by tissue specific endothelial adhesion molecules at inflammation sites. This allows the lymphocytes to transmigrate into gut mucosa.
Requires specialised post capillary microvascular endothelial cells (e.g. HEV) of lymphoid tissue.
What is the mucosal cell adhesion molecule?
MadCAM-1 (mucosal addressin cell adhesion molecule)
Where else is MadCAM-1 expressed?
Flattened endothelial cells in the lamina propria of SI and LI.
What are the symptoms and treatments of IBS
Symptoms:
- Recurrent abdominal pain
- Abnormal bowel motility
- Constipation/diarrhoea
Treatment:
- Diet modification (avoid certain foods)
- Constipation treatment (Eg fibre, stool softeners)
- Treat spasms/pain
- Management of stress.anxiety, depression, etc
What are the symptoms and treatment of coeliac disease?
Symptoms:
- Abdominal distension
- Diarrhoea
- Dermititis herpetiformis
Management:
1. Gluten free diet
Why is coeliac disease caused?
- Gliadin not broken down in stomach.
- Binds to SIgA in mucosal membrane.
- Gliadin-SIgA complex binds to transferrin receptor and transferred to lamina propria.
- Enzyme tissue transglutaminase cuts off amide group from protein.
- Deaminated gliadin phagocytosed by macrophages, presented by MHC 2.
- Immune system activated - epithelial cells destroyed
How is coeliac disease diagnosed?
AB blood tests (anti-gliadin, anti-tTG, anti-endomysial)
Biopsy test of duodenum
What are the symptoms and treatment for Crohns Syndrome?
Symptoms:
- Pain in affected area, RLQ commonly
- Diarrhoea/blood in stool
Treatment:
- Antiinflammatories, antibiotics
- Immunosuppressants (if severe)
- Liquid diet, low fibre
What are the mechanisms of Crohns syndrome?
- Pathogens (eg mycobacterium paratuberculosis, pseudomonas, listeria) trigger it
- Unregulated immune response causes cell destruction in GI tract
- NOD2 gene mutation, frame shift, may cause development of this disease.
What are the symptoms and treatment of ulcerative colitis?
Symptoms:
- Pain in LLQ (ulcers along inner LI surfaces).
- Severe, frequent diarrhoea
Treatment:
- Anti-inflammatory (e.g. sulfasalazine/mesalamine)
- Immunosuppressants if severe
- Colectomy
- Dietary manipulation
- Pre/probiotics
How is ulcerative colitis caused?
Autoimmune disorder - T cells destroy cell lining of the large intestine walls
Secondarily, diet and stress
What are the symptoms and treatment of cholera?
Symptoms:
- Vomiting, nausea
- Abdominal pain
- Dehydration and diarrhoea
Treatment:
- Fluids
- IV fluids/antibiotics
- Vaccination
How is cholera caused?
DIAGNOSED VIA STOOL TEST FOR BACTERIA OR BACTERIAL ANTIGEN
- Vibrio cholera - fecal-oral route (contaminated food)
- Bacteria reaches SI - flagellum propels it to epithelial cell - releases cholera toxin on close contact
- Cholera toxin causes Na, K, Cl, water efflux from epithelial cell.
In gut homing, where do the majority of lymphocytes proliferate?
In mesenteric lymph node
C. difficile management?
Isolate patient and give vancomycin
