Gut as an immune organ Flashcards
What is the normal ratio of CD8/CD4 cells in the gut?
1:4
between 1 and 4
Where will you find T lymphocytes in the gut?
Peyers patches
What are Peyers patches? Where are they found?
lymphoid follicles. Found in the small intestine.
What is the function of M cells?
They transport antigens (bacteria) across the epethilium (lumen) int the body to antigen presenting cells like Dendritic cells
What is the function of retinoic acid (vitamin A) in the Gut?
It is a homing beacon for immune cells to enter the gut from peyers patches
Which antigen presenting cell produces retinoic acid?
Dendritic cells using Retinal dehydrogenases
What is the function of Retinal dehydrogenases ?
Used by dendritic cells to convert Retinal into Retinoic acid
Describe the two mechanisms used to home CD4 and lymphocytes to the gut
CD4 T cells have an intergrin called α4β7. This binds to the ligand MadCAM which is an adhesion molecule only found on gut endothelial cells. When they bind CD4 cells can enter the lamina propria from the blood stream.
Enterocytes express CCL25 when its ligand CCR9 located on T cells binds, it guides T cells into intestinal tissue
What is the name for intestinal epithelial cells?
Enterocytes
Which cells in the gut can produce Immunoglobulin?
Gastrointestinal cells
Which Immunoglobulins are secreted into the gut?
IgA and IgM
What is the form of IgA in mucosal secretions and in the gut
Mucosal secretions- Dimer
Blood stream- monomer
How is IgA and IgM transported across the epithelium?
They bind to PIGR, which has an affinity for igA It is then transcytosed from the lamina propria into the lumen of the cell. J chain takes some of PIGR to form secretory subunit. When at other end becomes secretry iga and igm
What is the effector function of IgA?
What can IgA not do?
- Agglutination
- precipitation
1.complement activation
2.neutrophil chemotaxis
(recruit neutrophils)
3.phagocytosis
What is the most common cause of malabsorbtion?
coeliac disease.
What is coeliac disease? What is the genetic hallmark?
Autoimmune disorder of the small intestine.
People have the isoform HLA-DQ2 and HLA-DQ8 for HLA-DQ protein. 90% have HLA- DQ2
Where does the secretory IgA produced in breats milk come from?
B cells which have migrated from peyers patches to the mammary glands
What is the different between CD4 regulatory and CD4 helper cells? Which will you most likely find in the gut and why?
Regulatory suppress the immune response of there cells (tregs)
T helper cells help to initiate an immune response
Reg will be found most often
Which interlukins are mainly found in the gut? What is there function and which cell secretes them
Il-10 TGF- beta
Function- immunosurpressive
Produced by regulatory T cells
Describe the mechanism for the active transport of IgA and IgM into the gut
Once IgA has been secreted it moves form the Lamina propria to the lumen where it stops antigens from entering the mucosal surface.
PIGR receptors on the basal surface of epithelial cells have an affinity for dimeric IgA
When IgA binds to PIGR it is endocytosed into the epithelial cells and expelled into the lumen where it binds to SigA or SlgM for igm
As this occurs the J chain takes part of the PIGR receptor which forms the secretary components of the IgA antibody.
The secretary components protects IgA from enzymatic activity
What is the name of the two main immune cells found in the gut?
T cells and IgA cells
What is the normal ratio of CD4 to CD8 cells? What does this ratio represent?
A normal ratio is between 1 and 4
Reflects immune system health
Which cytokines are released by T regulatory cells? What is the name for these cytokines?
IL-10 and TGFβ which are anti inflammatory (immune suppressive) cytokines.
What can be taken up by M cells?
particles and macromolecules
Viruses
Bacteria and parasites
Why do antigens enter peyers patches through M cells?
M cells have They have No microvilli, Very little to no mucin layer
No lysozymes
They want to attract pathogens
Which parasite is taken up by M cells?
Name 2 particles taken up by M cells
Name 2 viruses taken up by M cells
Name 3 bacteria taken up by M cells
Parasite- Cryptosporidium Praticles- Ferritin and Cholera toxin Viruses- HIV-1 and Poliovirus type 1 Bacteria- Vibrio Cholera Salmonella typhi Escherichia coli
List the main lymphoid organs
Bone marrow
Lymph nodes
Spleen
List 7 regions in the body with a mucosal surface
Gastrointestinal Respiratory Genito-urinary Secretory glands: Lacrimal Salivary Mammary
List the different types of immunoglobulins produced in the Gi tract. What percentage of each does it produce?
IgA-80%
IgM-13%
IgG- 6%
IgD- 1%
What are the structural similarities and structural difference between IgA and IgM? If there is a reason for the structural component state it.
Similarities:
- 18 amino acid C-region tailpiece with a cysteine residue essential for polymerisation
- A single 15KDa “J chain” at the centre (glue) Necessary for secretion outside the mucosa
Differences-
IgA is a dimer in mucous secretions and a monomer in blood plasma
IgM is a pentamer (or hexamer) in plasma
What are the Histological symptoms of coelic disease?
Extensive malabsorbtion
complete villouse atrouphy
Cyptic hyperplasia
Increased IEL’s (intraepithelial lymphocytes)
What is the most common immunoglobulin found in breast milk?
Secretory IgA
What is Ferrograd?
A more gentle iron supplement, Contains Ferrous Sulphate which is released over a prolonged period of time.
What does MCV mean? How can it be calculated?
Mean corpuscular volume- average size and volume of red blood cells
Calculated using- hematocrit (Hct) and the red blood cell count (RBC)
What is Folate? What are its uses?
Vitamin B12 or B9
Uses:
Used to create red and white blood cells in the bone marrow.
Helps with DNA/ RNA production and repair.
Explain what IgA Anti-tTG antibodies are?
Tissue transglutaminase is an enzyme that fixes damage in your body. People with celiac disease often make antibodies that attack this enzyme. These are called anti-tissue transglutaminase antibodies.
What is ferritin? Where will you find it? What happens when its too low?
What is it? A protein in the body which binds to iron
Where will you find it? Mostly in the bone marrow, liver, spleen and skeletal muscle- not much in the blood.
What happens if ferritin levels are too low? Anaemia due to iron deficiency arises
What is Alkaline phosphatase? What does it mean when high amounts are found in those with Coeliac disease?
A group of isoenzymes, located on the outer layer of the cell membrane; they catalyze the hydrolysis of organic phosphate esters in the extracellular space
High amounts indicate Osteomalacia. Suggested to be associated with Chronic hypocalcemia and vitamin D deficiency.
Name two co-factors for Alkaline phosphatase. Where can you find it?
Zinc and magnesium
Located in many different tissues in the body. The one found in serum is secreted mainly from liver and bone
What is the dueodenum attached to superiorly and inferiorly? What is its function?
Superior- pyloric sphincter
Inferior- Jejunum
Function- First part of small intetsines, recives partially digested chyme. Uses chemicals to digest chyme further before later absorption. Uses chemicals from liver, gallbladder and pancrease
List the 4 layers of the gastrointestinal tract and the what can be found in each layer
1st (inner most)- Mucosa: Simple columnar epithelial, increase surface area and improve nutrient absorbtion
mucous glands secrete mucus into the lumen protect from friction and acidic chyme
2nd- Submucosa: Connective tissue, contains blood vessels and nerves
Contains proteins fibers to give strength and elasticity
3rd- Muscularis : Smooth muscle, Contracts to mix chyme and propel it through dodenum
4th- Serosa: simple squamous epithelium, smooth surface to prevent friction with surrounding organs. Secretes serouse fluid to reduce friction and keep duodenum moist
What is the pathophysiology of coeliac disease
- Inappropriate immune responce to gluten
- Gluten is composed of prolamines and glutenin
- prolamines contain epitopes which are presented by HLA-DQ2 or HLA-DQ8 and induce a CD4+ T-lymphocytes response
- Gliadin, break down product of gluten- impairs interenterocyte tight junctions
- This makes it able to pass through the epithelial barrier and activate T-lymphocytes located in the lamina propria
- Activated CD4+ T-lymphocytes produce high levels of pro-inflammatory cytokines, inducing either a T-helper
- These T helper cells can produce IFN-γ or cause the clonal expansion of B cells which differentiate in plasma-cells secreting anti-gliadin and anti-tissue-transglutaminase antibodies.
How does coeliac disease cause anemia?
Reduced surface area and inhibited absorbtion of iron
What else in the gut has been found to be associated with coeliac disease?
Increased intestinal Gram-negative and reduced Bifidobacteria
What are the diagnostic tests for coeliac disease?
Blood detection of IgA anti-tissue transglutaminase antibodies (tTGA) by enzyme-linked immunosorbent assay (ELISA)
Antibodies to deamidated gliadin peptides, IgA and IgG test
What is the treatment for coeliac disease?
Life-long gluten-free diet-
• Clinical improvement is achieved within a few weeks and the mucosal damage recovers in 1-2 years
• As vitamin B deficiency is common after an extended period on a GFD (gluten free diet), all patients are advised to take a gluten-free multivitamin
What are the benefits of prebiotic?
Prebiotics promote growth and survival of bacteria (and fungi)
Stimulate Bifidobacterium & Lactobacillus
What can be found in pre-biotics?
Non-digestible food ingredients Fructans Galactans Dietary fibres (inulin – asparagus, leek)
What are probiotics?
Live cultures found in dairy products or fermented foods
How does a Clostridium difficile infection occur? What are the symptoms and treatments?
Oppotunistic bacteria
Associated with use if broad-spectrum antibiotic
Symptoms- Causes watery diarrhoea,
abdominal pain
Treatment- Stop antibiotic use
Vancomycin / metronidazole
FMT
What is the mean total mucosal surface of the digestive tract and skin?
Digestive tract 32 m2
Skin 25 m2
