17. Gut Immunology (Shnyra) Flashcards

(58 cards)

1
Q

How do isolated lymphoid follicles mature?

A

Intestinal epithelial cells and dendritic cells present to cryptopatches, causing them to develop into isolated lymphoid follicles.

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2
Q

What is an isolated lymphoid follicle?

A

A single B cell follicle that acts as an inductive site for IgA production

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3
Q

What does exposure to microbiota do to assist the intestine in its development?

A

Stimulates the proliferation of intestinal epithelial cells encrypts, resulting in their increased depth.

In the small intestine, increases the density of Paneth cells.

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4
Q

How do activated T and B cells in the mesenteric lymph node arrive in the lamina propria / mucosa?

A

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.

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5
Q

Which T cells would interact with an APC carrying an MAMP if the result was Crohn’s disease?

What would their product be?

A

Th1 / Th-17

Interferon gamma, TNF, IL-17

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6
Q

What T cells would interact with an APC carrying an MAMP if the result was homeostasis?

What would the products be?

A

T reg cells

IL-10 and TGF-beta

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7
Q

What T cells would interact with an APC carrying an MAMP if the result was allergy?

What would the products be?

A

Th2

IL-4, IL-5, IL-13

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8
Q

How do undigested dietary carbohydrates, in the presence of commensal bacteria, decrease host response to the same commensal bacteria?

A

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.

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9
Q

What are the functions of short-chain fatty acids (like acetate) produced by commensal bacteria on the G.I.?

A

Increased T reg presentation.

Increased IgA effectiveness.

Increased production of mucus.

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10
Q

What three things are all of critical importance to the formation of induced Tregs for use in the guts to inhibit inflammatory responses?

A

TGF-beta.

Retinoic acid.

An enzyme called “IDO.”

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11
Q

Which type of hypersensitivity is involved in IgE mediated reactions?

Which type of hypersensitivity is involved in IgG or IgM immune complexes?

A

Type I hypersensitivity.

Type III hypersensitivity.

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12
Q

What mediates non-IgE mediated adverse food reactions?

A

T cells

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13
Q

Are T cell mediated adverse food reactions immediate onset or delayed in onset?

A

T cell mediated adverse food reactions are delayed in onset.

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14
Q

If someone has an immediate allergic reaction to food, what is probably mediating that reaction?

A

IgE

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15
Q

In terms of a food intolerance, what is considered “late phase / delayed in onset?”

A

4 to 28 hours after ingestion.

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16
Q

What is the basic process by which a type I allergy to food is initiated?

A

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.

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17
Q

How do complement proteins exacerbate food allergy symptoms?

A

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.

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18
Q

In what four ways do Treg cells prevent allergy?

A

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.

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19
Q

How do commensal microflora reduce the response to food allergens?

A

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.

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20
Q

What are the most common food allergies in the US?

A

Milk

Egg

Peanut

Soy

Wheat

Tree nuts

Fish

Shellfish

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21
Q

How do nuts (including peanuts) contribute to a more severe than usual allergic reaction?

A

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.

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22
Q

What is the most essential part of a food allergy diagnosis?

A

History of allergy symptoms

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23
Q

What foods are most commonly associated with anaphylaxis?

A

Peanuts.

Tree nuts.

Seeds.

Seafood.

Spices.

Celery.

Eggs.

Milk.

Some fruits.

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24
Q

What is the basic mechanism of type III hypersensitivity?

A

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.

25
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.
26
What are the two mechanisms for peanut allergy?
IgE mediated, and IgG mediated (non-IgE). IgG stimulates macrophages to produce platelet activating factor.
27
In what two locations has celiac disease not been identified?
Sub-Saharan Africa. East Asia.
28
What are the main genetic predisposing factors for celiac disease?
Presentation of HLA-DQ2 and HLA-DQ8
29
What autoantibody is specifically associated with celiac disease?
Anti-tissue transglutaminase 2 (anti-tTG2)
30
Why is gluten so difficult for humans to digest?
Gluten is proline-rich, and humans lack prolyl endopeptidases.
31
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
32
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.
33
What test is necessary to confirm celiac diagnosis?
Intestinal biopsy
34
What test can exclude the diagnosis of celiac disease?
HLA-DQ2 and HLA-DQ8 testing.
35
The gut associated lymphoid tissue (GALT) is the largest immune organ in the body. What are its two main components?
Isolated lymphoid tissue (ILT) and Peyer's pathces
36
Where and where do isoalted lymphoid follicles develop?
After birth, in the small and large intestines.
37
Do PP and ILF have afferent lymphatic vessels that deliver antigens to them?
Nope! They receive Ags directly from the lumen (epithelial surface) via Ag-transporting DCs.
38
Where do Ag-loaded DCs interact wiht local lymphocytes to indcue T-cell differentiation and T-cell-depedent B cell maturation?
T-cells are induced locally in PP, while T-cell-dependnet B-cell maturation takes place in the germinal centers and leads to the development of IgA-producing Plasma Cells in the lamina propria. Dimerized IgA is subseuently released into the intetinal lumen.
39
Which one is more effective to induce IgA-producing plasma cells....heat-killed bacteria or DCs that contain live bacteria?
DCs containing live bacteria (They come from M cells above PP --\> this allows for interaction of DCs with T and B cells in the PP and the migration of DCs to the raning mesentheric nodes.) This is rare becuse both commensal and pathologic bacterai is typically killed instatnly by macrophages inteh lamina propria. CDs cannot go further than the Lymph Nodes, they only traffic to that point.
40
What is required for a naive T-cell to differentiate into a T-reg cell?
Limited pro-inflammatory cytokines by APCs and an EXCESS of TGF-Beta Tregs supress Th1, 2, and 17
41
What are the effects of malnutrition on the GALT?
small PP fewer lymphocytes, Bcell, Tcells fewer antibody-forming cells less IgA
42
What are the effects of malnutrition on Lymph nodes?
reduced cellularity altered leukocyte trafficking altered antigen trafficking impaired barrier function fewer antibody-forming cells
43
What are the effects of malnutrition on the Thymus?
reduced thymc epithelium expnaded EC matrix thymocyte depeltion reduced thymic hormone
44
What are the effects of malnutrition on the Spleen?
reduced cellularity disroganized white pulp splenocyte depletion altered inflammatory environment
45
What are the effects of malnutrition on the Bone Marrow?
reduced cellularity expanded EC matrix altered stroma erythroid hypoplasia/dysplasia reduced erythropoietic progentior cells impaired myeloid cell maturation
46
Central Tolerance
When immature lymphocytes specific for self Ag encounter these Ag in the generative (central) lymphoid organs, they are - deleted - change in receptor (receptor editing) - develop into T-reg cells (CD4+ only)
47
Peripheral Tolerance
When mature self-reactive lyphocytes n peripheral tissue encounter self Ag, they are either: - inactivated - deleted (apoptosis) - suppressed by T-reg cells
48
What are the mediators of early allergic reactions?
**Preformed:** Histamine and TNF-Alpha **Granule assoicated:** tryptase, chymase, peroxidase Also, **bradykinin** and **platelet activting factor**
49
What are the mediators of late allergic reactions?
**Formed during degranulation:** LTC4, D4, E4, PGD2, Bradykinine, and Platelet Activating Factor **Generated after transcription:** IL-1, 2,3,4,5,&6, GM-CSF, TNF-Alpha
50
Histamine's modulating effects on Mast Cells during an allergic reaction
SM contraction increased vascuar permeability bronchospasm
51
Tryptase's modulating effects on Mast Cells during an allergic reaction
Trypsin-like activity anaphylaxis urticaria
52
Protaglandin E's modulating effects on Mast Cells during an allergic reaction
Pain vascular permeability
53
Prostaglandin D, Leukotrienes C4, D4, E4's modulating effects on Mast Cells during an allergic reaction
SM contraction increased vascular permeability
54
Bradykinine's modulating effects on Mast Cells during an allergic reaction
Vasodilator SM contraction
55
IL-5's modulating effects on Mast Cells during an allergic reaction
sputum eosinophils
56
What are the two mediators of accute GI response to allergen exposure?
PAF Serotonin (resulting in diarrhea)
57
What do T-cell derived IL-10 and TGF-Beta do in mediating/controlling a food allergy response?
Suppress Th2 immunity Inhibit mast cell reactivity Reduce IgE synthesis Increase IgG and IgA synthesis
58
Culprits in food- or drug-dependent exercise-induced anaphylaxis
Aspiring and NSAIDs seafood celery wheat cheese