Infection and immunology of Gut Flashcards
What are the four main mechanisms for protection from infection?
Physical Barriers
Chemical Barriers
Bacteria protection
Immunological protection
What are the physical barriers for mucosal defense?
Tight epithelial wall
Glycocalyx
Mucous and unstirred layer
Peristalsis to keep things moving along the GI tract
What are chemical barriers for mucosal defense?
Bacteriacidal enzymes from paneth cells and acid from stomach
What are bacteria protection for mucosal defense?
Commensal bacteria maintain immune system priming and may attack foreign species
What are immunological forms of mucosal defense?
Mucosa associated lymphoid tissue (MALT) rich in T cells and B cells whose components can be further categorized into G (Gut) ALT, B (bronchus) ALT etc
What are the two categories of GALT
Organised sites of lymphoid tissue such as Peyer’s patches in the small intestine and lymphocytes in mesenteria lymph nodules (where lymph from villi drain)
Disorganised sites inc lymphocytes in the lamina propria (mainly IgA) and lymphocytes in the interstitial space below the basolateral membrane of the epithelium (intra-epithelial cells)
What are Peyers patches?
Aggregated lymphoid follicles covered in follicle associated epithelium FAE
Where are Peyers patches found?
In small intestine with highest conc in distal ileum
What do Peyer’s patches do?
Function as immune sensors since they are capable of monitoring local bacteria and provide protection against pathogenic bacteria
What do Peyer’s patches contain
B cells
T cells
macrophages
dendritic cells
What are M cells?
Specialised enterocytes in follicle associated epithelium
What do M cells do?
Perform transcytosis of luminal bacteria, antigens and proteins.
What do M cells express?
IgA receptors that facilitate the transfer of IgA bacteria complex into peyer’s patches
What happens to antigens taken up by M cells?
Presented to lymphocytes for assessment and potential immunological response. Activated cells develop gut homing markers and migrate to mesenteric lymph nodes for proliferation
Why is IgA the most abundant antibody in the body even tho IgG is the most abundant circulating immunoglobulin?
IgA highly prevalent in mucosal secretions bc MALT associated with IgA plasma cells (B cell secreting a single antibody). The no. of activated plasma cells reflect the bacterial load and up to 90% gut B cells secrete IgA
What is SIgA
Secretatory IgA is a dimeric form of IgA
Where is SIgA produced?
In B cells in lamina propria.`
How is SIgA formed?
In plasma cell, two IgA bound together by J chain. Dimer binds to special receptor on external basolateral surface of enterocytes (pIgR). Receptor = secretatory component and binds to length of IgA dimer becoming SIgA
What does the secretory component of SIgA do?
Help IgA move through the enterocyte
Protects the antibody dimer from enzymatic and acidic degeneration
What does SIgA do?
Binds to pathogens, preventing adherence to mucosal wall.
How is antigen specific SIgA production stimulated?
Actions of M cells and dendritic cells in Peyer’s patches
What happens to mucosal lymphocytes once stimulated by an antigen?
Migrate into local mesenteric lymph nodes and drain into lymphatic sstem
What is lymphocyte homing
Transmigration of lymphocytes into gut mucosa stimulated by tissue specific endothelial adhesion molecules at the site of inflammation
What does lymphocyte homing require? - what special type of cells?
Specialised post capillary microvascular endothelial cells such as high endothelial venules of lymphoid tissue
What is L selectin? - where is it expressed
A carbohydrate binding lectin that is constitutively expressed on the surface of lymphocytes
What does L selectin do?
Mediates the low adhesive interactions that enable leukocytes to roll in post capillary venules and HEVs
What happens in HEVs?
L selectin mediates lymphocyte rolling by it’s binding to mucosal addressin cell adhesion molecule MAdCAM-1
Where is MAdCAM-1 expressed?
HEVs of peyer’s patches and mesenteric lymph nodes
Flattened endothelial cells localised in lamina propria of small and large intestines
What else does MAdCAM-1 do?
Enable lymphocyte recruitment in chronic gut inflammation
What are treatment options for irritable bowl syndrome?
Diet modification Treatment of constipation Treatment of spasms Management of stress, anxiety, depression Most of these target the symptoms^
Explain the role of dietary management to treat irritable bowel syndrome
Short chain carbohydrates cause symptoms, act as solutes that draw water from GI wall into lumen, causing visceral hypersensitivity (pain) and smooth muscles to spasm and cause diarrhea if water not reabsorbed properly.
These carbs are metabolised by bacterial flora that produce gas that causes even more bloating, spasm or pain
Recall the mechanism of coeliac disease
Gliadin is not broken down in the stomach, so reaches small intestine and binds to secretory IgA in the mucosal membrane.
Gliadin secretory IgA complex binds to transferrin receptor and are transferred to the lamina propria
Enzyme tissue transglutaminase cuts off amide group from protein
Deamidated gliadin phagocytosed by macrophages and presented by MHC II molecules
leading to activation of immune system - destruction of epithelial cels
What is gliadin?
33aa peptide component of gluten
What is the dietary management of coeliac disease?
Gluten free diet (wheat, barley, rye exclusion) and medication. Can also get gluten free foods on prescription.
Factors that affect compliance are lifestyle, eatin out, cross contamination at home and holidays
What is Crohn’s disease
Causes inflammation anywhere along GI tract - inflammatory bowl disease
Immune related disorder
What is an immune related disorder?
Immune system triggered by foreign pathogen in GI tract eg mycobacterium paratuberculosis, pseudomonas, and listeria
Inflam response large and uncontrolled and leads to distruction of cells in GI tract
Explain the dietary management and nutritional significance of Chron’s disease
liquid diet, low fibre/low residue, food reintroduction
Managing strictures: decrease obstruction, pain and gas production. Need to change diet so that food can get through the stricture; fibre can block the intestines. Avoid fibrous parts of fruit and vegetables (skins, seeds, woody stalks), whole- grains, nuts, seeds, gristle and skin from meat and fish, bones etc. May require different consistency e.g. liquidising
Explain the dietary management and nutritional significance of Ulcerative colitis
Dietary manipulation to minimise exacerbation of diarrhoea.
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
What is ulcerative colitis?
An autoimmune disorder where T cells destroy the cells lining the walls of the large intestine
