18. Gut Immunity, Nutrition, Adverse Food Reactions Flashcards
Homeostasis in gut mucosa is normally preserved by secretory ____-dependent exclusion of Ags and by suppression of proinflammatory responses by induced ____ tolerance
IgA; oral
Abrogation of oral tolerance and defects in the epithelial barrier may contribute to ___ allergies
Food
Oral tolerance depends on immune modulating microbial components and dietary factors, such as _____ and lipids
Vitamin A
T/F: Exclusive breastfeeding for 4 months and mixed feeding thereafter will probably promote oral tolerance to food allergens in newborns
True
2 major variables influencing the developing immunophenotype in infants
Induced oral tolerance
Productive immunity (secretory IgA mediated and systemic)
Oral tolerance occurs when antigens are captured in the _____ ______ and ______ _______ and carried to the mesenteric lymph node by _____ cells
Lamina propria; peyer’s patch; dendritic
In the lymph node, DCs stimulate expansion of induced ______ cells by a mechanism dependent on TGF-beta, _______, and indoleamine-2,3-dioxygenase
Treg; retinoic acid
Dendritic cells induce IgA-secreting plasma cells also through _____ dependent mechanisms
RA
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
IL-10
Environmental factors on allergic sensitization include vitamin ___, ____, and ______ which suppress inflammation
D, A, folate
What type of diet promotes inflammation?
High fat and medium chain triglycerides
The gut microbiota or its constituents can suppress allergic immune responses through the induction of _____ Cells
Effector mechanisms of allergies involve _____, basophils, and _____ cells
Treg
IgE; mast
What effect do the microbiota have on basophils and mast cells?
Supress them
iTregs suppress ____ cells that are central to generating IgE and allergic effector cells
Th2
What effect do long chain fatty acids have on allergy responses?
Suppress
Exposure to food allergens through non oral routes such as the skin may do what for allergy sensitization?
Predispose to sensitization, especially in the context of genetic barrier defects or inflammation
What is the difference between immune mediated and nonimmune mediated food reactions?
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
Adverse food reactions are initially divided into what 2 categories?
Toxic
Nontoxic - comprises pathogenic mechanisms that are both immune mediated and nonimmune mediated
What are some general nonimmune mediated mechanisms of nontoxic adverse food reactions?
Pharmacological
Enzymatic
Unclear causes such as certain irritants and psychosomatic responses
IgE mediated reactions constitute type ____ hypersensitivity while the non-IgE mediated reactions are type ____ hypersensitvity (IgG or IgM immune complex) or type ____ hypersensitivity
I; III; IV
IgE mediated food reactions are divided into what 2 categories?
Immediate
Late-phase
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
T
Most common foods triggering allergic reactions
Milk Egg Peanut Soy Wheat Tree nuts Fish Shellfish
What is the most common food allergy, with approximately 2% of infants having food intolerance or allergy to it?
Milk
[other most common are eggs and peanuts]
Within 3-5 years of life, 85% of children LOSE their sensitivity to what type of foods?
Milk
Eggs
Wheat
Soy
What type of allergies that begin in childhood continue into adulthood
Peanuts
Tree nuts
Fish
Shellfish
T/f: allergies to fruits and vegetables are common but usually not severe
True
Th2 cells are induced when DCs present peptides of allergens to naive _____ T cells in the presence of ____
CD4; IL-4
What cytokines do Th2 cells produce
IL-3 IL-4 (most important for allergy) IL-5 IL-9 IL-13
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 _______
IgE; FcE; sensitization
After sensitization has occurred, encountering the same allergen for a second time leads to degranulation of ______ and _____ leading to immediate hypersensitivity
Mast cells; basophils
Th2-type cytokines are important survival signals for what 3 cell types?
Mast cells
Basophils
Eosinophils
The Th2 cyotkines IL-9 and IL-13 are involved in _____ production
Mucous
What Th2 derived cytokines are involved in activation of mast cells, basophils, and eosinophils?
IL-3
IL-4
IL-5
What Th2-derived cytokines activate endothelial cells for Th2 homing?
IL-4
IL-13
What cytokines secreted by Treg cells suppress the actions of Th2 cells?
IL-10
TGF-beta
Activation of mast cells is central in food allergy. what is released with the granules that increases epithelial permeability?
Proteases like tryptase
Histamine
Also de novo synthesis of cytokines like IL-1b and TNF-a
______ and _______mediate the local acute GI response (diarrhea) to allergen exposure
___________ of mast cells is necessary for the local symptoms
PAF; serotonin
Mastocytosis
Disseminated Ags can trigger symptoms of _____ and _______
Distal reactions involve mechanisms dependent on _____ and _______
Urticaria; bronchospasm
Histamine; PAF
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?
IgE
Severe itching, hives Swelling of throat Bronchoconstriction Lowered BP Unconsciousness Death
Foods most frequently associated with anaphylaxis
Peanuts Tree nuts Seeds Seafood Spices Celery Eggs Milk Fruit
What effect does mast cell activation and granule release have on the GI tract?
Increased fluid secretion and increased peristalsis
Leads to expulsion of GI contents via diarrhea and/or vomiting
What effect does mast cell activation and granule release have on the airways
Decreased diameter, increased mucous secretion
Expulsion of airway contents via phlegm, coughin
What effect does mast cell activation and granule release have on blood vessles
Increased blood flow, increased permeability
Edema
Inflammation
Increased lymph flow
Carriage of Ag to LNs
What mast cell receptor binds and crosslinks specific IgE Abs to facilitate degranulation?
FceRI
Besides IgE, nut-induced anaphylaxis is also mediated by _____-induced activation of macrophages and neutrophils which also produce PAF
IgG
what effects do PAF and histamine have on vascular permeability and smooth muscle contractility?
Increase both
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
C3; C5
Tryptase; C3a; C5a
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?
Occupational asthma and rhinitis
Food allergy affecting the skin, GI or respiratory tracts
Wheat dependent exercise induced anaphylaxis
Contact urticaria
What is the most common variant of wheat allergy?
Wheat-dependent exercise-induced anaphylaxis (WDEIA)
Symptoms result from combination of causative food intake and physical exercise (as well as NSAIDs or alcohol)
Examples of food intolerance
Absence of enzyme
IBS
Food poisoning
Sensitivity to food additives
Recurring stress or psychological factors
Celiac disease
Main genetic predisposing factors to celiac disease
HLA-DQ2 and DQ8
[play key role in orchestrating adaptive immune response against gluten peptides]
Serum autoantibodies against the ubiquitous enzyzme _____ are specifically associated with celiac disease
Tissue transglutaminase 2 (TG2)
T/F: Ag-free MHC molecules are constitutively expressed on APCs
FALSE - no Ag-free MHC molecules are displayed on APCs
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
Proline
Glutamine; TG2
Peptides with a specific spacing of proline and glutamic acid bind to HLA class ____ on APCs
The majority of CD patients express the ________ heterodimer
II
HLADQ2.5
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
Lamina propria
Th1; myofibroblasts
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
Auto
IL-18, IFN-y, IL-21
IL-15
When should CD be an early consideration for a differential diagnosis in children?
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
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
IgA; transglutaminase
Anti-gliadin antibody
In testing for CD, measurement of total serum _____ can facilitate interpretation when the tTG IgA is low
IgA
What test is used to identify unusual cases of CD in which they come up seronegative?
Intestinal biopsy (which is actually recommended to confirm the dx in all cases)
Everybody as gluten peptides, and CD is virtually excluded if individuals lack _____ or _____ alleles
HLADQ2 HLADQ8
What is the number 1 environmental epidemic disease facing children in the developed world?
Allergy
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
False, they had NO IgE specific to CM protein and skin prick tests were negative
Reactions based on cow’s milk allergy are classified as delayed hypersensitivity type ____
IV
Skin prick or puncture tests tend to produce quick results in 15 mins. If these results are negative, what is the next step?
Intradermal tests
