18. Gut Immunity, Nutrition, Adverse Food Reactions

Question 1

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

Answer 1

IgA; oral

Question 2

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

Answer 2

Food

Question 3

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

Answer 3

Vitamin A

Question 4

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

Answer 4

True

Question 5

2 major variables influencing the developing immunophenotype in infants

Answer 5

Induced oral tolerance

Productive immunity (secretory IgA mediated and systemic)

Question 6

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

Answer 6

Lamina propria; peyer’s patch; dendritic

Question 7

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

Answer 7

Treg; retinoic acid

Question 8

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

Answer 8

RA

Question 9

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

Answer 9

IL-10

Question 10

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

Answer 10

D, A, folate

Question 11

What type of diet promotes inflammation?

Answer 11

High fat and medium chain triglycerides

Question 12

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

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

Answer 12

Treg

IgE; mast

Question 13

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

Answer 13

Supress them

Question 14

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

Answer 14

Th2

Question 15

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

Answer 15

Suppress

Question 16

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

Answer 16

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

Question 17

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

Answer 17

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

Question 18

Adverse food reactions are initially divided into what 2 categories?

Answer 18

Toxic

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

Question 19

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

Answer 19

Pharmacological
Enzymatic
Unclear causes such as certain irritants and psychosomatic responses

Question 20

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

Answer 20

I; III; IV

Question 21

IgE mediated food reactions are divided into what 2 categories?

Answer 21

Immediate

Late-phase

Question 22

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

Answer 22

T

Question 23

Most common foods triggering allergic reactions

Answer 23

Milk
Egg
Peanut
Soy
Wheat
Tree nuts
Fish
Shellfish

Question 24

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

Answer 24

Milk

[other most common are eggs and peanuts]

Question 25

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

Answer 25

Milk Eggs Wheat Soy

Question 26

What type of allergies that begin in childhood continue into adulthood

Answer 26

Peanuts Tree nuts Fish Shellfish

Question 27

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

Answer 27

True

Question 28

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

Answer 28

CD4; IL-4

Question 29

What cytokines do Th2 cells produce

Answer 29

``` IL-3 IL-4 (most important for allergy) IL-5 IL-9 IL-13 ```

Question 30

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 _______

Answer 30

IgE; FcE; sensitization

Question 31

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

Answer 31

Mast cells; basophils

Question 32

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

Answer 32

Mast cells Basophils Eosinophils

Question 33

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

Answer 33

Mucous

Question 34

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

Answer 34

IL-3 IL-4 IL-5

Question 35

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

Answer 35

IL-4 | IL-13

Question 36

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

Answer 36

IL-10 | TGF-beta

Question 37

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

Answer 37

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

Question 38

______ and _______mediate the local acute GI response (diarrhea) to allergen exposure ___________ of mast cells is necessary for the local symptoms

Answer 38

PAF; serotonin Mastocytosis

Question 39

Disseminated Ags can trigger symptoms of _____ and _______ Distal reactions involve mechanisms dependent on _____ and _______

Answer 39

Urticaria; bronchospasm Histamine; PAF

Question 40

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?

Answer 40

IgE ``` Severe itching, hives Swelling of throat Bronchoconstriction Lowered BP Unconsciousness Death ```

Question 41

Foods most frequently associated with anaphylaxis

Answer 41

``` Peanuts Tree nuts Seeds Seafood Spices Celery Eggs Milk Fruit ```

Question 42

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

Answer 42

Increased fluid secretion and increased peristalsis Leads to expulsion of GI contents via diarrhea and/or vomiting

Question 43

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

Answer 43

Decreased diameter, increased mucous secretion Expulsion of airway contents via phlegm, coughin

Question 44

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

Answer 44

Increased blood flow, increased permeability Edema Inflammation Increased lymph flow Carriage of Ag to LNs

Question 45

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

Answer 45

FceRI

Question 46

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

Answer 46

IgG

Question 47

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

Answer 47

Increase both

Question 48

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

Answer 48

C3; C5 Tryptase; C3a; C5a

Question 49

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?

Answer 49

Occupational asthma and rhinitis Food allergy affecting the skin, GI or respiratory tracts Wheat dependent exercise induced anaphylaxis Contact urticaria

Question 50

What is the most common variant of wheat allergy?

Answer 50

Wheat-dependent exercise-induced anaphylaxis (WDEIA) Symptoms result from combination of causative food intake and physical exercise (as well as NSAIDs or alcohol)

Question 51

Examples of food intolerance

Answer 51

Absence of enzyme IBS Food poisoning Sensitivity to food additives Recurring stress or psychological factors Celiac disease

Question 52

Main genetic predisposing factors to celiac disease

Answer 52

HLA-DQ2 and DQ8 [play key role in orchestrating adaptive immune response against gluten peptides]

Question 53

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

Answer 53

Tissue transglutaminase 2 (TG2)

Question 54

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

Answer 54

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

Question 55

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

Answer 55

Proline Glutamine; TG2

Question 56

Peptides with a specific spacing of proline and glutamic acid bind to HLA class ____ on APCs The majority of CD patients express the ________ heterodimer

Answer 56

II HLADQ2.5

Question 57

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

Answer 57

Lamina propria Th1; myofibroblasts

Question 58

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

Answer 58

Auto IL-18, IFN-y, IL-21 IL-15

Question 59

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

Answer 59

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

Question 60

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

Answer 60

IgA; transglutaminase Anti-gliadin antibody

Question 61

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

Answer 61

IgA

Question 62

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

Answer 62

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

Question 63

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

Answer 63

HLADQ2 HLADQ8

Question 64

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

Answer 64

Allergy

Question 65

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

Answer 65

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

Question 66

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

Answer 66

IV

Question 67

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

Answer 67

Intradermal tests