Gut as an Immune organ Flashcards
what is the surface area of the skin
25m2
what is the surface area of the mucosae
32m2
what enlarges the surface area of the mucosa
in the small intestine
- enlarged 1.6 times by place circularise
- enlarged 60-120 times by vili and microvilli
in the large intestine
- enlarged 6.5 times by the microvilli in the colon
the gut is lined by a…
single layer of epithelium, that is 30um across
what is giardiasis lambila
- bacteria that infect the gut
- they are a Flagellated parasitic microorganism
= they break the interface and prevent absorption leading to malabsorption
what are the two types of worms
Hook worms and tape worms
what do worms do
- they enjoy warm environment and reproduce
- they can create damage as they hook onto the gut and this creates wounding allowing bacteria to infect the gut
what is immunohistochemsitry
- this is using immunology as a way of staining cells
what is the CD4/CD8 ratio a reflection of
- immune system health
- normal ratio is between 1 and 4
what is peyer’s patch
- Organised lymphoid follicles found in the small intestine
How many Peyer’s patch is there
there is about 100 of them in the human GI tract
what type of lymphocyte is in Peyer’s patch
T lymphocyte – clustered everywhere in the gut, specifically here
what are all the types of cells in the Peyer’s patch
M cells
T lymphocytes
Dendritic cells
what do M cells do
- they transport gut antigens across the epithelium into the body
- they take bacteria from the gut
- allow antigen presenting cells (APC) to access the gut content
what do dendritic cells do within in Peyer’s patch
- Dendritic cells and sit ontop of the M cell or can extend through the peyers patch so they sample within the gut directly
what happens if you kill all the bacteria in the gut
leads to an immature Peyer’s patch
how do T and B lymphocyte gut homing work
- Peyers patch samples the kind of bacteria that we have, if there are harmful bacteria then we need to make B cells and T cells to destroy them
- APC released and go into the lymph nodes
- They need to go back into the gut
- APC talk to naïve T cells and prim them to go to the gut
- They use vitamin A – retinoic acid
- They have alcohol dehydrogenases and retinal dehydrogenase which converts retinol to retinal first then to retinoic acid
- It modifies the DNA of T cells to prim it to go to the gut
- The retinoic acid tells the nuclei of the T cells to form Alpah4beta7 and CCR9
- The APC cells have equipped the T cells with two receptors that allow them to go to the gut, they respond to signals that are only present in the gut
- Endothelial cells in the gut and in the gut only express MadCAM (this is a singla from the gut telling the T cell to move to the gut) this is the ligand for alpha4beta7, it binds to the receptor, the T cells get stuck to the cells in the gut
- They then go to the lamina propria,
- In the lamina propria the intestinal epithelial cells (enterocytes) express CCL25 which is the ligand for CCR9 (chemokine) – the chemokine molecule makes the cell move
- Its informed of the kind of bacteria that is in the gut
in the gut what is the main immunoglobulin
IgA
what shape is IgA
dimer in mucous secretions but not in plasma
what shape is IgM
pentamer in plasma
what happens to IgA when it is transported across the epithelium
- IgA is activately transported across epithelium by the polymeric Ig receptor and is secreted with the gut where it becomes SigA and SigM
what disease has an IgA deficiency
2% of people with coeliac disease has an IgA deficiency
describe the IgA and IgM
- Both contain an 18 amino acid Constant-region tailpiece with a cysteine residue essential for polymerisation
what is the J chain in IgA and IgM necessary for
- A single 15KDa “J chain” (the “glue” between two Fc regions of the antibody. Necessary for secretion outside the mucosa)
what is the function of the mucosal antibodies
- Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms.
- SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities
- You can live without Immunoglobulin A
why do lactation of breast milk some B cells leave Peyer’s patch and make IgA
because. ..
- Breast endothelium expressed MadCAM
- Breast epithelium expresses CCL25
what does B cells (that were in the gut) do in breast milk
- During lactation some B cells which leave peyer’s patch move to the breast and make IgA
- Breast endothelium expressed MadCAM
- Breast epithelium expresses CCL25
- When it is there it activate B cells and this leads to antibody production and secretion so produces SigA and SigM
- It is secreted into the milk which goes into the gut of the baby, the baby was previously IgA deficient
if malabsorption happens in the economically developed world what has caused it
coeliac disease
what is coeliac disease
- Autoimmune disorder of the small intestine that occurs in genetically predisposed people
what do people with celiacs disease have and what does it lead to
- Over 95% of people with coeliac have the isoform of DQ2 or DQ8 of the human leukocytes antigen HLA-DQ (HLA is MHC in humans)
- This leads to uncontrolled immune response, cytokine inflammation interleukins produced and a big surge of different antibodies
- This will destroy the enterocytes and make it possible for the gut to form the vili
