Immunology Of The Gut Flashcards
GI tract
- surface area of 200m squared
- Massive antigen load
- 10^14 resident bacteria in the microbiota
- State of restrained activation
Dual immunological role - tolerance vs active immune response (tolerance would be food antigens and commensal bacteria) (immune reactivity would be pathogens)
What did germ free mice show
maldevelopment of small intestine
- fewer Peyer’s patches
- angiogenin 4 expressed less
4 Major phyla of bacteria
Bacteroidetes, firmicutes, actinobacteria, proteobacteria
Provide traits we have not had to evolve individually
Genes in gut flora 100 times our own genome
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Dysbiosis
Symbionts regulate
Pathobionts cause inflammation
Commensals do not effect the equilibrium
Xenobiotics - small chemical compounds that enter unnaturally - drugs, pollutants
Dysbiosis is related to a multitude of disorders, including autism (4-EPS), cancers (short chain fatty acids), pancreatic diseases (bile acids)
Cancer development may also include overgrowth of certain biota - so cancer patients may be given probiotics
Mucosal defenses physical barrier
- Epithelial barrier
- Mucus layer - goblet cells
- Epithelial monolayer - tight junctions
- Paneth cells (in small intestine)
- At the base of the crypts of Lieberkuhn
- Secrete antimicrobial peptides (defensins) & lysozyme
- Peristalsis
Chemical mucosal defense
Enzymes
Ph
Commensal bacteria occupy an ecological niche
Immunological barriers
MALT (Mucosa Associated Lymphoid Tissue)
GALT (Gut Associated Lymphoid Tissue)
MALT (Mucosa Associated Lymphoid Tissue)
- Found in submucosa below the epithelium, as lymphoid mass containing lymphoid follicles
- Follicles are surrounded by HEV postcapillary venules, allowing easy passage of lymphocytes
- Oral cavity rich in this tissue
HEVs are found in lymph nodes and other secondary lymphoid organs but not in the spleen
GALT (Gut Associated Lymphoid Tissue)
- Responsible for both adaptive and innate immune responses through generations of lymphoid cells and Abs
1. Non organised - Intra-epithelial lymphocytes - make up 20% of intestinal epithelium, such as T cells and NK cells
- Lamina propria lymphocytes
- Less surface area in large intestine so more Ig-A secretion
2. Organised - Peyer’s patches (small intestine)
- Caecal patches (large intestine)
- Isolated lymphoid follicles
- Mesenteric lymph nodes (encapsulated)
Peyer’s patches:
Act as immune sensors
Mainly found in the distal ileum
Aggregated lymphoid follicles covered with follicle associated epithelium (FAE)
FAE - no goblet cells. no secretory IgA, lack microvilli
Organised collection of naive T and B cells
Development requires exposure to bacterial microbiota
- 50 in last trimester of pregnancy, 250 by teens
Antigen uptake via M (microfold) cells within the FAE
- M cells express IgA receptors, and facilitate transfer of IgA bacteria complex into the Peyer’s patches
Antigen sampling
Trans-epithelial dendritic cells capture an antigen from beyond the epithelial barrier, and then relocate to the mesenteric lymph nodes
B cell Adaptive Response
- Mature naive B cells express IgM
- This switches to IgA on antigen presentation
- T-cells and epithelial cells secrete cytokines which influence B cell maturation
- B cells further mature and become IgA secreting plasma cells
- These populate the lamina propria
Formation of Secretory IgA (sIgA)
- Up to 90% of gut B cells secrete IgA
- sIgA binds the luminal antigen to prevent adhesion and therefore invasion
Lymphocyte homing and circulation
Peyer’s patches - antigen presented and activated
Travels to mesenteric lymph node (lymphocyte proliferation)
This goes to the thoracic duct, into circulation
It can then go back to lamina propria, or skin, tonsils, or BALT
Tight junctions formed of a4b7 integrins where T cells bind causing cytokine release and MAdCAM-1s which causes cell adhesion . Directs circulating T cells to peyers patch to mount response
What is the life span of enterocytes and goblet cells of the small bowel?
36 hours
- Enterocytes are the first line of defence against GI pathogens, may be directly affected by toxins
- This means diminishing the effects of agents which interfere with cell function
Cholera
Caused by Vibrio cholerae serogroups O1 and O139
Releases cholera enterotoxin on contact with small intestine epithelium which causes increased adnelytate cyclase activity this increased water pump activity
Transmitter via faecal oral route, contaminated food and water
Main symptoms - diarrhoea, dehydration, vomiting, abdominal pain
Diagnosis: Bacterial culture taken from faecal sample on selective agar, or dipstick test may be performed
Treatment: Oral rehydration
Dukoral - oral, inactivated vaccine against the pathogen - useful where there is a lack of clean water