7 Gut Immunity, Nutrition, And Adverse Food Reactions Flashcards
Homeostasis in the gut mucosa is normally preserved by secretory _____ dependent immune exclusion of Ags and by the suppression of ____ by _____.
IgA
Pro inflammatory responses
Induced oral tolerance
Food allergy is the consequence of abrogation of ____ due to inappropriate interactions between ____ and ____.
Oral tolerance
Genes and the environment
A defect in the _____ may underlie food allergen sensitization in the gut, ___, and ____.
Epithelial barrier
Skin
Airways
Oral tolerance depends on immune-modulating ___ and dietary factors like ____ and _____.
Microbial components
Vitamin A and lipids
Breastfeeding will aid in the formation of what?
Oral tolerance
This depends on the balance between induced oral tolerance and productive immunity (secretory IgA mediated and systemic)
Immunological homeostasis
Factors playing a role in the immunological homeostasis
Highest risk when what overlaps?
Genetics Age Breastfeeding Nutrition Dietary factors Antigen Exogenous microbial exposure Indigenous microbiota Epithelial permeability Atopic (allergic) phenotype
Lifestyle, genetics, and environment
T cell activation and differentiation is modulated by _____ between _____ and ____.
Co-stimulatory signals (cytokines and ligand)
APCs and naive (memory) T cells
Exaggerated immune response to micro flora (TH1 immune medated response)
Allergy/food adverse reaction is a ____ immune mediated response
Crohn’s disease
TH2
Innate immune cells are in close proximity to the _____ in the lumina propria
_____ can sample antigens from the lumen and take to the mesenteric lymph node; it then acts as a APC and stimulates ____.
Epithelial layers
Dendritic cells
T cells
_____a converts T cells to Treg cells to induce ___.
____ migrates locally to lamina propria to control inflammation
____controls the production and secretion of IgA antibodies
What controls the development of T reg cells?
TGF beta
Systemic suppression
T reg cells
TGF beta
TGF beta, retioic acid (to produce phenotype of dendritic cell to make Treg) and IDO control the development of Treg cells
Normally positively affect and control the immune response
It can suppress the allergic immune response through the induction of ____.
Micro flora (suppress the development of inflammatory cells)
Treg cells
Vitamins ____ suppress inflammation
What promotes inflammation?
D, A, folate
High fat diet
Effector mechanisms of a food allergy involve what?
They are suppressed by what?
IgE, basophils, and mast cells
Microbiota suppress basophils and mast cells
ITregs suppress Th2, which generate IgE
Normal tolerance is associated with increased presence of _____.
Blocks development of allergic reactions mediated by ____.
Treg cells
IgE and mast cells and basophils
Dendritic cell that acquire food antigen, instead of turning on Treg, they promote ____.
TH2 causing and immune response…food allergy
Dysbiosis can lead to what?
Caused by?
Dysregulation of the immune system and to inflammation
Environmental factors like Antibiotics and medications
What two things co-evolve?
What are they affected by and how?
Microbiota and immune system
Malnutrition: microbiota act as a barrier to enteropathogen infection. This barrier function can be disrupted by malnutrition
Recurrent infections predisposed to nutrient deficiencies and impaired intestinal mucosal barrier function
Food allergies are classified in two categories
Caused by?
Immune-mediated (food allergy and celiac disease)
Nonimmune mediated (food intolerances)
Ag-specific (adaptive) immune response that occurs reproducibly on exposure to a given food
Two main adverse food reactions
Toxic
Non-toxic: pathogenic mechanisms that are both immune-mediated and non-immune mediated
Non-immune mediated mechanisms include what?
Pharmacological, enzymatic, and unclear causes like irritants and psychosomatic responses
Food allergy contributed to two groups of immune reactions?
What type hypersensitivity is IgE mediated reactions?
Non-IgE mediated reactions?
IgE mediated:divided into immediate onset reactions and late-phase
Non-IgE-mediated: T-cell mediated
Type I hypersensitivity
Type III and Type IV
They are delayed in onset, occurs 4-28 hours after ingestion of offending food
Allergens presented to naive T cell by ______.
Naive T cell to TH2 by ____.
TH2 cell produces cytokines _____ that affect _____.
___ induces B cell to begin secreting IgE antibodies in circulation.
Dendritic cell
IL-4
IL3, IL4, IL5, IL9, IL13
Basophils, eosinophil, mast cells
IL-4
Cytokines secreted by TH2 cells:
Increase mucus production
Stimulate mast cells, basophils, eosinophil
Stimulate IgE production from B cells
Stimulate endothelial cells
IL9, IL13
IL3, IL4, IL5
IL4, IL13
IL4, IL13
*** all these effects are suppressed by Treg cell’s cytokines (IL10, TGF beta)
Cytokines secreted by Treg
IL10, TGF beta
Suppress the effects of Th2 cells
Activation of ____ is central in food allergy.
Location?
What does it release?
Mast cells
Close to capillaries
Proteases (destroy)
Histamine
Cytokines (activate endothelial cells)
During local IgE mediated food allergy, dendritic cell exposes antigen to T cells that release cytokines stimulating mast cell which induce _____.
Diarrhea and stimulates platelet activating factor for clotting in the local tissue
During systemic IgE mediated food allergy, antigen is absorbed by ____ and transferred to periphery.
Mast cells activated in skin, lung, of systemic circulation and release ____ causing ______.
Mesenteric lymph nodes
Histamine and platelet activation factor
Systemic immune response
___ is the number one epidemic diseases in children.
Most common food allergy is ____.
Suffer from ___ allergy.
What is strange about the testing?
What are they classified as?
Allergy
Milk
Cow’s milk protein allergy (CMA)
No IgE specific for CM proteins in blood***
Skin prick test with CM Ags are negative
Delayed hypersensitivity Type IV***
Most severe form of systemic reaction in which several different parts of the body experience allergic reactions to foods at the same time
Caused by what?
Effects?
Anaphylaxis
Sudden release of multiple chemical mediators that events mediated by IgE antibodies like mast cell activation and granule release
Itching, hives, throat swelling, bronchoconstriction, hypotension, unconsiousness, death
Effects of anaphylactic reactions
GI: increased fluid secretion, increased peristalsis->expulsion of GI contents with vomiting and diarrhea
Resp: decreased diameter, increased mucus secretion-> expulsion of airway contents with phlegm and coughing
Blood vessels: increased blood flow, increased permeability->edema, inflammation, increased lymph flow and carriage of antigen to lymph node
No signs during sensitization phase of a food allergy
Why?
Don’t interact with antigen. Ready in 14 days
First response with the antigen, no local or systemic response
Multiple pathways of anaphylaxis are mediated by either ___ or ____ and their respective Fc receptors.
Mast cells activated by ___ and play a central role in food-induced anaphylaxis
It’s mediators are ___ which increase ____.
Nut-induced anaphylaxis is mediated by ___ induced activation of ____ that produce PAF
IgE or IgG
IgE
Histamine and PAF; vascular permeability (that release exudation with C3 and C5) and smooth m contractility
IgG; macrophages and neutrophils
Nut allergy can be induced by IgE
What complements are in allergy and anaphylaxis?
___ is released from mast cells and act on C3 and C5 to locally generate ____ which further activate mast cells to exacerbate the symptoms.
C3a and C5a
Tryptase
C3a and C5a
Wheat allergy is ____ mediated.
Classified into what?
IgE
Occupational asthma
Food allergy
Wheat-dependent exercise-induced anaphylaxis (WDEIA): combination of food and physical exercise and NSAID or alcohol)
Contact urticaria
Food intolerance is not mediated by ____.
Types:
Absence of an _____ needed to fully digest food.
Irritable bowl syndrome
Food poisoning
immune response
Enzyme
Chronic condition can cause cramping, constipation, and diarrhea
Toxins such as bacteria in spoiled food can cause severe digestive symptoms
Types of food intolerances
Sensitive to food additives
Recurring stress
Celiac disease: chronic digestive condition triggered by gluten
Systemic immune disorder caused by a permanent sensitivity to gluten
Positive for ___ antibodies.
What molecules are the main genetic predisposing factor?
Why?
Celiacs Disease
Anti-tTG2 antibodies (diagnostic factor)
HLA-DQ2 and DQ8: play a role in orchestrating an adaptive immune response agains gluten peptides
(Most will have or will develop an autoimmune disorder)
Class II MHC molecules are found on ____.
In celiacs disease, what class II MHC are present?
Professional APC
HLA-DQ2 and DQ8
Proline-rich protein that is poorly digested in the SI because lack of ____.
Rich in glutamine residues
Peptides of 10-50 AA in length are formed and left incompletely digested
Some of the glutamine in the peptides can be deaminated by tissue enzyme ____ resulting in the formation of ____.
Prolyl endopeptidases
Gluten
TG2
Negatively charged glutamic acid residues
Peptides with proline and glutamic acid like in ____, bind to ____ on APC cells
Gluten
HLA class II (HLADQ2)
In the immuno-pathogenic response, ____ are generated.
Tissue damage occurs in a _____ manner.
Self-reactive T cells (CD4, CD8) because type of autoimmunity
Type IV hypersensitivity
Gluten causes a T cell mediated inflammatory response in the ____ that damages the mucosa and leads to ____.
____ continues as long as gluten is ingested.
Immune-pathogenic response makes ___.
Proximal SI
Malabsorption
Chronic inflammatory response
Anti-TG2 Abs
Healthy people have ____ peptides, but no disease because don’t have ___.
Gluten
HLA
Repeated activation of immune response leads to collateral damage including what?
Formation of fibroblasts from matrix degrading and mucosal remodeling (substitution of CT)
Fibroblasts exposed to TGF beta become myofibroblasts producing higher level of CT
Peptides highly resistant to intestinal proteases can reach the lamina propria
Cross-linking and deamination of gluten peptides by _____ creates potent immunostimulatory epitopes presents by ____.
Gluten peptides
Transglutaminase 2
HLADQ2 or HLADQ8 on APC
Pathogenesis of CD:
Activated CD4 T cells secret mainly ___ cytokines like ___ that induce the release of MMPs by ____ resulting in mucosal remodeling and villus atrophy.
TH1
IFN gamma
Myofibroblasts
Pathogenesis of CD:
Th2 cytokines produced and drive the production of auto-Ab to ____.
Other cytokines play a role in polarizing and maintaining the TH1 response like ____
This cytokine links the adaptive immune response to the innate.
Gluten and TG2
IL18, IFN gamma, IL21
IL15
Test for celiac disease with a measurement of ___ antibody to human tissue transglutaminase (TTG)
Why?
To exclude the diagnosis of CD, use ____.
IgA
Can facilitate interpretation when the tTG IgA is low (could be IgA deficiency)
Intestinal biopsy to identify unusual case of seronegative CD and confirm diagnosis
HLADQ2 and DQ8 testing
This reaction occurs 6-8 hours after an initial type I hypersensitivity response
Late-phase reaction
Food allergens are resistant to _____.
Gastric digestion; in order to induce an IgE dependent response, allergen peptides are loaded into HLA class II
Activates endothelium
Amplifies Th2 cell response
Increase vascular permeability
CT matrix remodeling
Chemotaxis
TNF alpha
IL4
Histamine
Tryptase
CCL3
Anaphylaxis occurs in an individual after reexposure to an antigen to which that person has produced specific ___ antibodies
IgE
These immune cells use the express FcERI
Mast cells, basophils, and eosinophils
