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*GIGU I > 18. Gut Immunity, Nutrition, Adverse Food Reactions > Flashcards

18. Gut Immunity, Nutrition, Adverse Food Reactions Flashcards

1
Q

Homeostasis in gut mucosa is normally preserved by secretory ____-dependent exclusion of Ags and by suppression of proinflammatory responses by induced ____ tolerance

A

IgA; oral

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2
Q

Abrogation of oral tolerance and defects in the epithelial barrier may contribute to ___ allergies

A

Food

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3
Q

Oral tolerance depends on immune modulating microbial components and dietary factors, such as _____ and lipids

A

Vitamin A

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4
Q

T/F: Exclusive breastfeeding for 4 months and mixed feeding thereafter will probably promote oral tolerance to food allergens in newborns

A

True

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5
Q

2 major variables influencing the developing immunophenotype in infants

A

Induced oral tolerance

Productive immunity (secretory IgA mediated and systemic)

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6
Q

Oral tolerance occurs when antigens are captured in the _____ ______ and ______ _______ and carried to the mesenteric lymph node by _____ cells

A

Lamina propria; peyer’s patch; dendritic

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7
Q

In the lymph node, DCs stimulate expansion of induced ______ cells by a mechanism dependent on TGF-beta, _______, and indoleamine-2,3-dioxygenase

A

Treg; retinoic acid

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8
Q

Dendritic cells induce IgA-secreting plasma cells also through _____ dependent mechanisms

A

RA

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9
Q

Gut-homing iTregs are expanded in the lamina propria by ______ expressing macrophages

These iTregs can then suppress systemic immune responses including allergic sensitization in an Ag specific manner

A

IL-10

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10
Q

Environmental factors on allergic sensitization include vitamin ___, ____, and ______ which suppress inflammation

A

D, A, folate

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11
Q

What type of diet promotes inflammation?

A

High fat and medium chain triglycerides

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12
Q

The gut microbiota or its constituents can suppress allergic immune responses through the induction of _____ Cells

Effector mechanisms of allergies involve _____, basophils, and _____ cells

A

Treg

IgE; mast

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13
Q

What effect do the microbiota have on basophils and mast cells?

A

Supress them

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14
Q

iTregs suppress ____ cells that are central to generating IgE and allergic effector cells

A

Th2

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15
Q

What effect do long chain fatty acids have on allergy responses?

A

Suppress

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16
Q

Exposure to food allergens through non oral routes such as the skin may do what for allergy sensitization?

A

Predispose to sensitization, especially in the context of genetic barrier defects or inflammation

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17
Q

What is the difference between immune mediated and nonimmune mediated food reactions?

A

Immune mediated are Ag-specific and occur reproducible on exposure to a given food - such as food allergies and celiac disease

Nonimmune mediated are formerly known as food intolerances

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18
Q

Adverse food reactions are initially divided into what 2 categories?

A

Toxic

Nontoxic - comprises pathogenic mechanisms that are both immune mediated and nonimmune mediated

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19
Q

What are some general nonimmune mediated mechanisms of nontoxic adverse food reactions?

A

Pharmacological
Enzymatic
Unclear causes such as certain irritants and psychosomatic responses

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20
Q

IgE mediated reactions constitute type ____ hypersensitivity while the non-IgE mediated reactions are type ____ hypersensitvity (IgG or IgM immune complex) or type ____ hypersensitivity

A

I; III; IV

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21
Q

IgE mediated food reactions are divided into what 2 categories?

A

Immediate

Late-phase

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22
Q

Non-IgE mediated food reactions are believed to be _____ cell mediated

They are typically delayed in onset, occurring 4 to 28 hours after ingestion of offending foods

A

T

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23
Q

Most common foods triggering allergic reactions

A 
Milk
Egg
Peanut
Soy
Wheat
Tree nuts
Fish
Shellfish
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24
Q

What is the most common food allergy, with approximately 2% of infants having food intolerance or allergy to it?

A

Milk

[other most common are eggs and peanuts]

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25
Q

Within 3-5 years of life, 85% of children LOSE their sensitivity to what type of foods?

A

Milk
Eggs
Wheat
Soy

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26
Q

What type of allergies that begin in childhood continue into adulthood

A

Peanuts
Tree nuts
Fish
Shellfish

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27
Q

T/f: allergies to fruits and vegetables are common but usually not severe

A

True

28
Q

Th2 cells are induced when DCs present peptides of allergens to naive _____ T cells in the presence of ____

A

CD4; IL-4

29
Q

What cytokines do Th2 cells produce

A 
IL-3
IL-4 (most important for allergy)
IL-5
IL-9
IL-13
30
Q

In the presence of IL-4, B cells switch to produce _____ and bind to specific _____ receptors on mast cells and basophils. This is known as _______

A

IgE; FcE; sensitization

31
Q

After sensitization has occurred, encountering the same allergen for a second time leads to degranulation of ______ and _____ leading to immediate hypersensitivity

A

Mast cells; basophils

32
Q

Th2-type cytokines are important survival signals for what 3 cell types?

A

Mast cells
Basophils
Eosinophils

33
Q

The Th2 cyotkines IL-9 and IL-13 are involved in _____ production

A

Mucous

34
Q

What Th2 derived cytokines are involved in activation of mast cells, basophils, and eosinophils?

A

IL-3
IL-4
IL-5

35
Q

What Th2-derived cytokines activate endothelial cells for Th2 homing?

A

IL-4

IL-13

36
Q

What cytokines secreted by Treg cells suppress the actions of Th2 cells?

A

IL-10

TGF-beta

37
Q

Activation of mast cells is central in food allergy. what is released with the granules that increases epithelial permeability?

A

Proteases like tryptase

Histamine

Also de novo synthesis of cytokines like IL-1b and TNF-a

38
Q

______ and _______mediate the local acute GI response (diarrhea) to allergen exposure

___________ of mast cells is necessary for the local symptoms

A

PAF; serotonin

Mastocytosis

39
Q

Disseminated Ags can trigger symptoms of _____ and _______

Distal reactions involve mechanisms dependent on _____ and _______

A

Urticaria; bronchospasm

Histamine; PAF

40
Q

Anaphylaxis is a reaction resulting from sudden release of multiple chemical mediators, as a result of events mediated by ____ antibodies

What are the effects of these mediators?

A

IgE

Severe itching, hives
Swelling of throat
Bronchoconstriction
Lowered BP
Unconsciousness
Death
41
Q

Foods most frequently associated with anaphylaxis

A 
Peanuts
Tree nuts
Seeds
Seafood
Spices
Celery
Eggs
Milk
Fruit
42
Q

What effect does mast cell activation and granule release have on the GI tract?

A

Increased fluid secretion and increased peristalsis

Leads to expulsion of GI contents via diarrhea and/or vomiting

43
Q

What effect does mast cell activation and granule release have on the airways

A

Decreased diameter, increased mucous secretion

Expulsion of airway contents via phlegm, coughin

44
Q

What effect does mast cell activation and granule release have on blood vessles

A

Increased blood flow, increased permeability

Edema
Inflammation
Increased lymph flow
Carriage of Ag to LNs

45
Q

What mast cell receptor binds and crosslinks specific IgE Abs to facilitate degranulation?

A

FceRI

46
Q

Besides IgE, nut-induced anaphylaxis is also mediated by _____-induced activation of macrophages and neutrophils which also produce PAF

A

IgG

47
Q

what effects do PAF and histamine have on vascular permeability and smooth muscle contractility?

A

Increase both

48
Q

The release of mast cell derived mediators such as histamine cause an increase in vascular permeability and the resulting exudation likely contains complement components _____ and _____

______ released from activated mast cells acts on these components to generate _____ and ____ which activate mast cells to further exacerbate symptoms

A

C3; C5

Tryptase; C3a; C5a

49
Q

Ingested wheat can cause IgE mediated wheat allergies in childrens and adults

Depending on route of exposure, wheat allergy is classified into what 4 categories?

A

Occupational asthma and rhinitis

Food allergy affecting the skin, GI or respiratory tracts

Wheat dependent exercise induced anaphylaxis

Contact urticaria

50
Q

What is the most common variant of wheat allergy?

A

Wheat-dependent exercise-induced anaphylaxis (WDEIA)

Symptoms result from combination of causative food intake and physical exercise (as well as NSAIDs or alcohol)

51
Q

Examples of food intolerance

A

Absence of enzyme

IBS

Food poisoning

Sensitivity to food additives

Recurring stress or psychological factors

Celiac disease

52
Q

Main genetic predisposing factors to celiac disease

A

HLA-DQ2 and DQ8

[play key role in orchestrating adaptive immune response against gluten peptides]

53
Q

Serum autoantibodies against the ubiquitous enzyzme _____ are specifically associated with celiac disease

A

Tissue transglutaminase 2 (TG2)

54
Q

T/F: Ag-free MHC molecules are constitutively expressed on APCs

A

FALSE - no Ag-free MHC molecules are displayed on APCs

55
Q

Gluten is a _____-rich that is poorly digested in small intestine due to lack of prolyl endopeptidases

Gluten is also rich in _____ residues, some of which can be deamidated by tissue enzyme ____, resulting in formation of their negatively charged form

A

Proline

Glutamine; TG2

56
Q

Peptides with a specific spacing of proline and glutamic acid bind to HLA class ____ on APCs

The majority of CD patients express the ________ heterodimer

A

II

HLADQ2.5

57
Q

Gluten peptides that are highly resistant to intestinal proteases reach the ______

Crosslinking and deamidation of these peptides by TG2 creates potent immunostimulatory epitopes that are presented via HLADQ2 or HLADQ8 on APCs

Activated CD4 T cells secrete mainly ____ cytokines such as IFN-y which induce the release of MMPs by _______ resulting in mucosal remodeling and villus atrophy

A

Lamina propria

Th1; myofibroblasts

58
Q

In addition to pathogenesis of Th1 cytokines released in response to resistant gluten peptides, Th2 cytokines are produced driving the production of ______-abs to gluten and TG2

Other cytokines such as ____, _____, or ______seem to play a role in polarizing and maintaining the Th1 response

______ links the adaptive immune system to innate immune responses

A

Auto

IL-18, IFN-y, IL-21

IL-15

59
Q

When should CD be an early consideration for a differential diagnosis in children?

A

Children with failure to thrive and persistent diarrhea

GI symptoms like recurrent abd pain, constipation, vomiting

Non-GI symptoms such as dermatitis herpetiformis, dental enamel hypoplasia, osteoporosis, short stature, delayed puberty, and iron-deficient anemia resistant to iron

60
Q

To test for CD, the initial step is to measure ____ Ab to human tissue ________ enzyme

Note that because of inferior accuracy, the ______ test is no longer recommended

A

IgA; transglutaminase

Anti-gliadin antibody

61
Q

In testing for CD, measurement of total serum _____ can facilitate interpretation when the tTG IgA is low

A

IgA

62
Q

What test is used to identify unusual cases of CD in which they come up seronegative?

A

Intestinal biopsy (which is actually recommended to confirm the dx in all cases)

63
Q

Everybody as gluten peptides, and CD is virtually excluded if individuals lack _____ or _____ alleles

A

HLADQ2 HLADQ8

64
Q

What is the number 1 environmental epidemic disease facing children in the developed world?

A

Allergy

65
Q

T/F: a high percentage of children with cow’s milk allergy showed IgE specific to cow milk protein in their blood and skin prick tests were positive

A

False, they had NO IgE specific to CM protein and skin prick tests were negative

66
Q

Reactions based on cow’s milk allergy are classified as delayed hypersensitivity type ____

A

IV

67
Q

Skin prick or puncture tests tend to produce quick results in 15 mins. If these results are negative, what is the next step?

A

Intradermal tests

*GIGU I (67 decks)

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