Food Allergy - Nanda 3/15/16 Flashcards
food allergies as public health concern
- primarily seem to affect children/adolescents
- tree nuts, peanuts are leading causes of fatal/near-fatal anaphylaxis
- no cure! just avoidance
food allergy response, centered around ____
definition of true food allergy
immunoglobulin E
- minor form (.5-1%); least abundant Ig, found only in mammals
- attached mast cells, basophilic cells, infl cells in mucous membranes: lungs, intestines, skin
- gives IgE the strongest response!
- defense against parasites (helminths)
therefore, true food allergy is one where you get elevated IgE levels against an antigen from that food
two stages of food allergy progression
1. sensitization
- food allergen passes through int epi cell → interact with APCs (antigen-presenting cells)
- antigen gets engulfed, processed, presented on MHC receptors on the APC
- MHC receptors → interact with T cells → interact with T helper cells → program B cells (memory cells)
- B cells produce specific IgEs against the allergen
2. elicitation
- IgEs made by B cells move over to mast cells and bind to FCεRI
- ε : name comes from heavy chains on IgE
- eventually (after a number of times) the allergen will induce crosslinking of IgE on mast cell surface
- in response, mast cell will release inflammatory factors!
TH1/TH2 hypothesis
theory as to why some people develop allergies and others don’t
insufficient theory
balance of T helper cells exists - having a lot more of one than the other can determine whether you have a predisp to allergies
there might be genetic factors, environmental factors that affect the balance
- TH1 (class 1 helper cells) respond primarily to infection (viruses, bacteria, protozoa)
- TH2 (class 2) more recently evolved to respond to parasites, allergens
seems to be an antagonistic relationship between the two classes → turn TH1 productio non = turn TH2 production off and vice versa via cytokines, interferons
incomplete bc other things also matter: not just ratio that matters, also absolute levels of TH1 and TH2, levels of Treg cells
protein food allergens
the majority of food allergens are proteins
peanuts : Ara h 1-8 : seed storage proteins
shellfish : tropomyosin : muscle protein
cow milk : lactalbumin : lactose biosynth
allergens contain one or more epitopes: fragments that bind IgE
cross reactivity
developing allergy to one thing means increased risk of developing allergy to another thing (ex. cow’s milk allergy, 92% risk for goat’s milk allergy)
why?
structural similarity may drive cross-reactivity (ex. birch pollen allergen & apple allergen)
Celiac disease
not typical food allergy
peptide binding directly: gliadin (Pro/Gln-rich peptide in wheat) binds strongly to HLA type DQ2 → drives immune response
- Pro-rich sequence in gliadin makes it resistant to protease degradation → increases concentration in sm intesting → increased absorption, immune rxn
transglutaminase exacerbates this response : activates peptides, antibody formation
- tissue transglutaminase activates peptides → makes HLA DQ2 binding even more potent
- transglutaminase can crosslink with gliadin peptides → results in formation of antibodies against complex → stronger autoimmune rxn
role of gastric digestion in mediating allergy
- gastric acid suppression interferes with proteolysis and food degradation in stomach
- pepsinogen is kept in zymogen form until pH 2
- drugs that elevate pH can slow rate of degradation → allow epitopes that should have been degraded stick around long enough to be recog’d by immune system
in allergies, epitopes are surviving long enough to be absorbed → triggering allergic rxn
- something about proteins and epitopes themselves makes them structurally stable to digestion
pre- vs pro-biotics
prebiotics: complex sugars that are consumed by gut bacteria; do not offer direct nutrition to humans
probiotics: bacteria intended to supplement gut bacteria
influence of breastmilk on infant microbiome
hypothesis: mom-to-child microbiome connection!
- bacteria travel from mom’s gut → bloodstream → mammary glands
- 200 human milk oligosacchs (HMOs) that support growth of beneficial gut bacteria (don’t provide nourishment)
- prevent growth of harmful bacteria by preventing binding to int epi
- milk contains several lactic acid bacteria → secrete H2O2 for killing harmful pathogens
studies re: microbiome and allergy devpt
correlation between gastric acid suppression during pregnancy → childhood asthma
commensal bacteria protect against allergen sensitization [mice]
hygiene hypothesis
parents keeping kids “too clean”, super protective
- understimulation of TH1 leads to imbalance in favor of TH2
- understimulation of Tregs
- antibiotics → effect flora
- food additives (ex. adjuvants: sulfites, nitrites, nitrates, MSG, aspartame)
oral immunotherapy
small amt of allergen administered orally or sublingually
- 6 mos later → skin prick test rxns reduced
- 18 mos later → specific IgEs signif lower
also…
- IgG also elevated
- stimulation of Treg levels
anti IgE and receptor therapies
studies have found that…
- mAbs against IgE or FCεRI broadly reduce sensitivity to many antigens (incl common allergens)
- allosteric binding to IgE heavy chains → dissoc of IgE from receptor
