7. Gut Immunology Flashcards
How do isolated lymphoid follicles mature?
Intestinal epithelial cells and dendritic cells present to cryptopatches, causing them to develop into isolated lymphoid follicles.
What is an isolated lymphoid follicle?
A single B cell follicle that acts as an inductive site for IgA production
What does exposure to microbiota do to assist the intestine in its development?
Stimulates the proliferation of intestinal epithelial cells encrypts, resulting in their increased depth.
In the small intestine, increases the density of Paneth cells.
How do activated T and B cells in the mesenteric lymph node arrive in the lamina propria / mucosa?
They enter the mesenteric lymph node, enter the bloodstream through the thoracic duct, travel throughout the entire bloodstream, and then home in and enter the lamina propria / mucosa.
Which T cells would interact with an APC carrying an MAMP if the result was Crohn’s disease?
What would their product be?
Th1 / Th-17
Interferon gamma, TNF, IL-17
What T cells would interact with an APC carrying an MAMP if the result was homeostasis?
What would the products be?
T reg cells
IL-10 and TGF-beta
What T cells would interact with an APC carrying an MAMP if the result was allergy?
What would the products be?
Th2
IL-4, IL-5, IL-13
How do undigested dietary carbohydrates, in the presence of commensal bacteria, decrease host response to the same commensal bacteria?
Undigested dietary carbohydrates can be fermented into acetate.
Acetate can increase the presentation of IL-10 + T regs.
T regs decrease host response to commensal bacteria.
What are the functions of short-chain fatty acids (like acetate) produced by commensal bacteria on the G.I.?
Increased T reg presentation.
Increased IgA effectiveness.
Increased production of mucus.
What three things are all of critical importance to the formation of induced Tregs for use in the guts to inhibit inflammatory responses?
TGF-beta.
Retinoic acid.
An enzyme called “IDO.”
Which type of hypersensitivity is involved in IgE mediated reactions?
Which type of hypersensitivity is involved in IgG or IgM immune complexes?
Type I hypersensitivity.
Type III hypersensitivity.
What mediates non-IgE mediated adverse food reactions?
T cells
Are T cell mediated adverse food reactions immediate onset or delayed in onset?
T cell mediated adverse food reactions are delayed in onset.
If someone has an immediate allergic reaction to food, what is probably mediating that reaction?
IgE
In terms of a food intolerance, what is considered “late phase / delayed in onset?”
4 to 28 hours after ingestion.
What is the basic process by which a type I allergy to food is initiated?
Allergens are eaten by a dendritic cell, and then presented to a naïve T cell. IL-4 induces the naïve T cell to become a Th2 cell, which produces more IL-4 to induce B cells to produce IgE. The Th2 cell also produces other cytokines to recruit the other effector cells of allergy: basophils, eosinophils, and mast cells.
How do complement proteins exacerbate food allergy symptoms?
Mast-derived mediators increase vascular permeability, allowing complement proteins C3 and C5 to escape from the capillary. Mast cell-released enzyme tryptase clips C3/C5 into C3a/C5a. C3a/C5a further activates mast cells, and exacerbates symptoms.
In what four ways do Treg cells prevent allergy?
Treg cells prevent B cells from producing IgE.
Treg cells suppress mucus overproduction by the goblet cells of the enterocytes.
Treg cells desensitize mast cells and basophils.
Treg cells suppress Th2 cell homing to tissues.
How do commensal microflora reduce the response to food allergens?
They contain microbe associated molecular patterns which favor Treg formation.
They produce acetate and butyrate through fermentation which up regulates Treg formation.
They inhibit mast cells and basophils.
What are the most common food allergies in the US?
Milk
Egg
Peanut
Soy
Wheat
Tree nuts
Fish
Shellfish
How do nuts (including peanuts) contribute to a more severe than usual allergic reaction?
Nuts and peanuts can convert C3 into C3a, stimulating macrophages basophils and mast cells to produce platelet activating factor and histamine. C3a will stimulate the cells even as the allergic antigen is stimulating them, resulting in a more severe affect.
What is the most essential part of a food allergy diagnosis?
History of allergy symptoms
What foods are most commonly associated with anaphylaxis?
Peanuts.
Tree nuts.
Seeds.
Seafood.
Spices.
Celery.
Eggs.
Milk.
Some fruits.
What is the basic mechanism of type III hypersensitivity?
An antigen attaches to an antibody, then the Fc region attaches to an Fc receptor on an endothelial cell.
Other antibodies attach to the bound antigen, forming and immune complex.
This immune complex activates the classical complement system, which releases anaphylotoxins C3a, C5a, and C4a.
If a patient does not have IgE antibodies for cows milk, but has a history of allergic reaction to it, what type of hypersensitivity do they have?
Type IV hypersensitivity.
What are the two mechanisms for peanut allergy?
IgE mediated, and IgG mediated (non-IgE).
IgG stimulates macrophages to produce platelet activating factor.
In what two locations has celiac disease not been identified?
Sub-Saharan Africa.
East Asia.
What are the main genetic predisposing factors for celiac disease?
Presentation of HLA-DQ2 and HLA-DQ8
What autoantibody is specifically associated with celiac disease?
Anti-tissue transglutaminase 2 (anti-tTG2)
Why is gluten so difficult for humans to digest?
Gluten is proline-rich, and humans lack prolyl endopeptidases.
What are the two antibodies found in celiac disease against tissue transglutaminase 2?
Which one is most commonly assayed for?
IgA and IgG
anti-tTG2 IgA
What might cause a false negative in an anti-tTG2 antibody assay?
IgA deficiency.
An anti-tTG2 antibody assay is testing for specifically anti-tTG2 IgA. Some patients have low IgA overall, and in these patients, the assay would come back low – a false negative.
What test is necessary to confirm celiac diagnosis?
Intestinal biopsy
What test can exclude the diagnosis of celiac disease?
HLA-DQ2 and HLA-DQ8 testing.
