7 Gut Immunity, Nutrition, And Adverse Food Reactions Flashcards by Abby Finder

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

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Food allergy is the consequence of abrogation of ____ due to inappropriate interactions between ____ and ____.

Oral tolerance

Genes and the environment

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A defect in the _____ may underlie food allergen sensitization in the gut, ___, and ____.

Epithelial barrier

Skin

Airways

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Oral tolerance depends on immune-modulating ___ and dietary factors like ____ and _____.

Microbial components

Vitamin A and lipids

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Breastfeeding will aid in the formation of what?

Oral tolerance

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This depends on the balance between induced oral tolerance and productive immunity (secretory IgA mediated and systemic)

Immunological homeostasis

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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

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T cell activation and differentiation is modulated by _____ between _____ and ____.

Co-stimulatory signals (cytokines and ligand)

APCs and naive (memory) T cells

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Exaggerated immune response to micro flora (TH1 immune medated response)

Allergy/food adverse reaction is a ____ immune mediated response

Crohn’s disease

TH2

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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

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_____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

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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

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Vitamins ____ suppress inflammation

What promotes inflammation?

D, A, folate

High fat diet

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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

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Normal tolerance is associated with increased presence of _____.

Blocks development of allergic reactions mediated by ____.

Treg cells

IgE and mast cells and basophils

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Dendritic cell that acquire food antigen, instead of turning on Treg, they promote ____.

TH2 causing and immune response…food allergy

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Dysbiosis can lead to what?

Caused by?

Dysregulation of the immune system and to inflammation

Environmental factors like Antibiotics and medications

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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

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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

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Two main adverse food reactions

Toxic

Non-toxic: pathogenic mechanisms that are both immune-mediated and non-immune mediated

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Non-immune mediated mechanisms include what?

Pharmacological, enzymatic, and unclear causes like irritants and psychosomatic responses

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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

*** 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