11 Immunology Flashcards
Q: How does the microbiota vary at different points in the GI tract? (4)
A: Loads in the mouth is because we put lots of dirty things into it, including food, fluid, cutlery, air etc.
Into the stomach, the low pH kills lots of bacterial populations (except H. pylori).
The number is kept low in the duodenum, jejunum and proximal ileum because of paneth cells and Peyer’s patches (discussed in detail later).
Beyond the ileocaecal valve the number of microorganisms increases markedly.
Q: What are the gastrointestinal mucosa’s four main mechanisms for protection from infection?
A: Physical barriers:
Chemical barriers:
Bacteria protection:
Immunological:
Q: How can the gastrointestinal’s mucosa act as a physcial barrier to protect against infection? (5)
A: a tight epithelial wall, glycocalyx, mucous and unstirred layer. Also, persitalsis to keep things moving along the GI tract
Q: How can the gastrointestinal’s mucosa act as a chemical barrier to protect against infection? (2)
A: bacteriacidal enzymes from paneth cells, and acid from stomach
Q: How does the gastrointestinal’s mucosa act as a barrier to protect against infection in terms of bacterial protection? (2)
A: commensal bacteria maintain immune system priming and may attack foreign species.
Q: How does the gastrointestinal’s mucosa act as a barrier to protect against infection in terms of immunological protection? (3)
A: Mucosa-associated lymphoid tissue (MALT) rich in T cells and B cells, whose components can be further categorised into GALT (Gut-associated lymphoid tissue), BALT (Bronchus-associated lymphoid tissue) etc.
Q: What is GALT? What are the 2 categories of it based on? Describe each and describe 2 examples for each.
A: Gut-associated lymphoid tissue
two categories depending on organisation
- organised sites of lymphoid tissue such as Peyer’s patches in the small intestine and lymphocytes in mesenteria lymph nodules (i.e. where the lymph from the villi drain)
- disorganised sites which include lymphocytes in the lamina propria (mainly IgA-secreting B-cells) and lymphocytes in the interstitial space below the basolateral membrane of the epithelium (called intra-epithelial cells)
Q: Apart from GALT, what other immunological structures are there to protect against infection in the GI tract? function?
A: although not technically GALT, there are Kuppfer cells in the liver which can phagocytose bacteria
Q: What do peyer’s patches consist of? Where are they found? highest concentration where?
A: aggregated lymphoid follicles covered with follicle associated epithelium (FAE)
small intestine, having highest concentration in the distal ileum
Q: What is the function of peyer’s patches? capable of? (2)
What are peyer’s patches rich in? (4)
A: function as “immune sensors” since they are capable of monitoring local bacteria, and provide protection against pathogenic bacteria
B cells, T cells, macrophages and dendritic cells
Q: What does the development of peyer’s patches require? How many do we have by the last trimester of gestation? When do we reach our maximum number? how many is this?
A: requires exposure to bacterial flora (i.e. they are barely present in animal models that are born and reared in sterile environments)
Humans have about 50 by the last trimester of gestation, and hit the maximum of about 250 by their teenage years.
Q: What is FAE? where is it found? What does FAE consist of?
A: follicle associated epithelium (FAE)
- covering aggregated lymphoid follicles of peyer’s patches
FAE contains specialized enterocytes or M cells where enterocytes are just intestinal absorptive cells = simple columnar epithelial cells found in the small intestine
Q: Where are M cells found? Main function? What do they express? aids?
A: follicle associated epithelium (FAE)
- covering aggregated lymphoid follicles of peyer’s patches
main function of M cells is to perform transcytosis of luminal bacteria, antigens and proteins
(uptake and transport of antigens from the gut lumen
to the underlying mucosal immune system)
M cells express IgA receptors, facilitating transfer of IgA-bacteria complex into the peyer’s patches
Q: Antigen uptake in peyer’s patches is a combined effort by? (2) Describe (5).
A: specialised M-cells and dendritic cells
- M cells express IgA receptors, facilitating transfer of IgA-bacteria complex into the peyer’s patches
- these antigens are then presented to the lymphocytes
- for assessment and potential immunological response
- Activated cells develop gut homing markers (follows idea that where immune cells are activated= best place for them to act)
- and migrate to mesenteric lymph nodes for proliferation
Q: What are the M cells an ideal entry point for? eg? Why? (2) Summarise.
A: potential pathogens eg Vibrio cholerae
- accessibility of M cells on the mucosal surface
- ability to transcytose particulate material
M cells can transport a diverse array of mucosal microorganisms across the intestinal epithelial barrier
Q: How is the FAE distinguished? (3) What lies beneath it? describe (5).
A: (follicle associated epithelium)
aside from having M cells, is distinguished by a reduced number of goblet cells and enterocytes
sub-epithelial dome (SED)
-a diffuse region of dendritic cells (DCs), naive B cells, CD4+ and CD8+ T cells, and macrophages
Q: What can happen to particles transported by the M cells from the lumen? (4)
A: can be captured in SED (subepithelial dome (SED) region) by immature DCs
which then migrate to B-cell follicles // and parafollicular T-cell zones
and become mature DCs
Q: What is the apical membrane of M cells specialised for? Features? (2) What else specialised M cells for this role? allows? What can they produce to aid?
A: uptake and transport of antigens
reduced glycocalyx, general lack of membrane hydrolytic enzymes
dramatic reduction of lysosomes may allow M cells to transport microorganisms into the lymphoid follicles without altering their antigenic properties
pro-infammatory cytokine interleukin 1
Q: During embryonic and postnatal development, each crypt in the intestine is a? What happens next?
Describe the development of M cells and other cells in relation to it. (6)
A: clonal unit whose cells differentiate into multiple types as they migrate
Cells on the villous side of the crypt differentiate into absorptive enterocytes, goblet cells and enteroendocrine cells
The cells on the FAE side of the crypt acquire the phenotype of absorptive enterocytes, M cells and, rarely, goblet cells
Q: How do IgA and IgG differ in abundance? Explain.
A: Although IgG is the most abundant circulating immunoglobulin in the body, IgA is the most abundant antibody in the body.
Explanation: IgA is highly prevalent in mucosal secretions because MALT is associated with large numbers of IgA(+) plasma cells (B cells secreting a single antibody). The number of activated plasma cells reflects the bacterial load and up to 90% gut B-cells secrete IgA.
Q: What is the structure of SIgA/secretory IgA? produced by? in? transported?
How? (3)
A: SIgA is a dimeric form of IgA- two IgA molecules are bound together by a J-chain
produced by B cells (IgA plasma cells) in the lamina propria and transported across the enterocyte into the interstitial space
- The dimer binds to a special receptor on the external basolateral surface of enterocytes (polymeric immunoglobulin receptor; pIgR)
- This receptor becomes the secretory component and binds to the length of the IgA dimer, becoming SIgA (secretory component protects the antibody dimer from enzymatic and acidic degradation)
- SIgA is then endocytosed into the epithelial cell and actively transported within a vesicle to the apical membrane, where it is exocytosed into the gut lumen
Q: What does SIgA do? How is it stimulated? (2) in?
A: binds to pathogens, preventing their adherence to the mucosal wall
Antigen-specific SIgA production is stimulated by the actions of M-cells and dendritic cells in Peyer’s patches.
Q: Describe the process of lymphocyte circulation. (4)
A: 1. Mucosal lymphocytes in Peyer’s patches = stimulated by an antigen
- migrate into the local mesenteric lymph nodes and drain into the lymphatic system
- reach the systemic circulation via the thoracic duct and spread throughout the body in the blood
- These lymphocytes remain in the blood until activated by tissue-sepecific endothelial adhesion molecules at the site of inflammation, which permit transmigration of the lymphocytes into the gut mucosa. This is called lymphocyte homing
Q: What does lymphocyte homing require? eg?
A: requires specialised post-capillary microvascular endothelial cells, such as the high endothelial venules (HEVs) of lymphoid tissue
Q: What is L-selectin? Where is it expressed? role?
A: carbohydrate-binding lectin
- constitutively expressed on the surface of lymphocytes and mediates the low adhesive interactions that enable leukocytes to roll in postcapillary venules and HEVs
Q: What is the role of L-selectin in HEVs?
A: mediates lymphocyte rolling by its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1)
Q: Where is MAdCAM-1 expressed? (3) Role?
A: -HEVs of Peyer’s patches
- mesenteric lymph nodes
- 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 by binding to L selectin on lymphocytes- aids rolling
Q: Draw a diagram for lymphocyte circulation.
A: REFER
Q: What are the symptoms of irritable bowel syndrome? (3) Treatment? (4)
A: Recurrent abdominal pain
Abnormal bowel motility
Constipation and/or diarrhea
Diet modification - Avoiding certain foods such as apples, beans, cauliflowers.
Treatment of constipation - soluble fiber, stool softeners and osmotic laxatives
Treatment of spasms and pain - anti-diarrheals, anti-muscarinic
Management of stress, anxiety, depression
