Mucosal immunology of the GI tract Flashcards
What is the physiological function of the GI tract?
Food digestion and absorption
Immune regulation
Describe the cellular structure of the small intestine
Villi and crypts
Goblet cells, paneth cells and Peyer’s patches
Describe the cellular structure of the epithelium of the large intestine?
Crypts, no villi No paneth cells Lots of goblet cells and mucus No Peyer's patches Enterocyctes do defence
What does the mucosal immune system of the GI tract have to do?
Capture the antigen
Initiate the local immune response
Carryout effector functions to clear any infection
Where does antigen capture occur?
In Peyer’s patches and directly across the epithelium by dendritic cells
What are the specialized epithelial cells in Peyer’s patched called?
M cells
What happens to antigens when they meet M cells?
M cells take up the antigen by endocytosis and phagocytosis
Antigen is transported across the M cells in the vesicles and released at the basal surface
Antigen is bound by dendritic cells, which activate T cell
Where does initiation of the intestinal immune response occur?
In the mesenteric lymph nodes
What are lymph nodes a hub for?
Maximising T lymphocyte exposure to antigens
What two types of cell drain to the lymph nodes with antigens?
Dendritic cells and B cells
What happens to T lymphcytes when they are activated?
The loose CCR7 meaning they can no longer re-circulate
Where do activated T cells drain to?
They drain via the mesenteric lymph nodes to the thoracic duct and return to the gut via the bloodstream
What is the most important antibody in the gut/
IgA (80% of immunoglobin in the gut)
IgM 15% and IgG 5%
How is IgA produced and released?
Produced by a IgA-secreting cell
Binds to receptor on basolateral face of epithelial cell
Endocytosis
Transcytosis to apical face of epithelial cell
Release of IgA dimer at apical face of epithelial cell
What does secreted IgA do?
Secreted IgA binds to pathogens and toxins and neutralizes them
While being secreted, IgA can bind to toxins that have entered epithelial cells and export them
What are intraepithelial lymphocytes?
Cells that sit within the epithelial barrier
90% are T cells, 80% of which are CD8+ (effector T cells) that do not need activated
What are the two recognition mechanisms for intraepithelial lymphocytes?
Virus specific recognition (TCR/CD8 cells)
Stress specific recognition (NK cells)
What is the default state of the gut immune system?
Systemic hyporesponsiveness
What immunoglobin causes an aggressive response?
IgE
What are the distinctive anatomical features of the mucosal immune system?
The tissues sit in a very intimate relationship between mucosal epithelial and lymphoid tissue
There are organised lymphoid structures unique to mucosal sites
Specialized antigen uptake mechanisms
What is the hygiene hypothesis?
A theory that suggests a young child’s environment can be “too clean” to effectively stimulate or challenge the child’s immune system to respond to various threats during the time their immune system is maturing
What mechanism eliminates most intestinal infections?
Innate mechanisms
What are the innate receptors?
Pattern recognition receptors (PRR)
What happens when pattern recognition receptors are activated?
Gene transcription and production of cytokines, chemokines and defensins
What is coeliac disease?
Damage to the small intestine due to an abnormal reaction to the gluten antigen
It has a T cell component
Results in malnutirion
(not an allergy)
What is the score to measure the scale of coeliac disease?
MARSH score
How does the antigen cause villi destruction?
The gluten peptides activate mucosal epithelial cells to express MIC molecules
Intraepithelial lymphocytes are activated by MIC molecules binding to the expressed NKG2D
They kill the epithelial cells by programmed cells death through the recognition of the stress receptor
What is a second killing mechanism in coelic disease?
Enzyme modifies peptides so they can bind to MHC class II molecules
Bound peptide activates gluten-specific CD4-T cells
Activated T cells kill mucosal epithelial cells
How is coeliac disease diagnosed?
Serology and genetics in most children
What other tests are down when diagnosis coeliac disease to avoid a false negative?
IgA deficiency tests
also if they are have IgA deficiency they go for biopsy as 10x more likely to have the disease
What is inflammatory bowel disease?
Altered function and imbalance of the relationship between prevention of invasion by pathogens and tolerance to innocuous foods and commensal microorganisms
What are the two subtypes of inflammatory bowel disease?
Crohn’s and ulcerative colitis.
Which inflammatory bowel disease has the deepest inflammation?
Crohn’s disesae
Which inflammatory bowel disease has the greatest genetic influence?
Crohn’s disease
Where does Crohn’s disease affect?
Any part of the GI tract, commonly the distal ileum and colon
Where does ulcerative colitis affect?
Restricted to the rectum and colon
What is the difference between CD and UC?
In CD there are healthy parts of the intestine mixed in between inflammed areas
In UC it is continuous inflammation of the colon
UC only occurs in the inner most lining of the colon whereas CD can occur in all the layers of the bowel walls
What is the treatment for inflammatory bowel disease?
Non-specific anti-inflammatory and immunosuppresive drugs
What causes a food allergy?
Type I hypersensitivity reaction initiated by crosslinking of allergen specific IgE on the surface of mast cells with the specific allergen
