Food Intolerance Flashcards
(159 cards)
1
Q
What are the most common reasons for food “allergy”?
A
irritants- curry and acidity; gas; food poisoning; biochemical
2
Q
What are hte common biochemical food intolerances?
A
lactose intolerance and fructose/sorbitol malabsorption
3
Q
Give examples of non-IgE mediated food allergies?
A
food protein induced enterocolitis syndrome; food protein induced proctocolitis and enteropathies
4
Q
Give examples of mixed IgE and non-IgE mediated food allergies?
A
cows milk protein allergy and eosinophilic oesophagitis/gastroenteritis
5
Q
What is the definition of food allergy?
A
ingestion of a small amoutn of food elicits an abnormal immunologically mediated clinical response
6
Q
When is the reaction with IgE mediated food allergy?
A
mins to 2hrs
7
Q
When is the typical onset with cell-mediated food allergy?
A
1hr to 8 hrs
8
Q
What is the difference in prevalence between IgE-mediated food allergies in children and adults?
A
children: 5-7%; adults: 1.4%- Young
9
Q
What is the difference between perceived and actual prevalence of food allergy in adults?
A
actual- 1.4% vs perceived- 20.4% - Young
10
Q
What are the most common food allergies?
A
milk; egg; peanut; tree nuts; seafood; shellfish; soy and wheat
11
Q
what are the features of allergenic foods?
A
polar glycoproteins; heat; acid and protease resistant
12
Q
What is the pathway in IgE mediated HS?
A
mast cell/basophil with specific IgE on surface, if allergen binds and cross-links activates the cell and results in degranulation with release of inflammatory mediators
13
Q
What are hte features of mucosal tolerance?
A
epithelial barrier with IgA; low Ag presentation; no specific IgE; immunosuppressive environment- IL-10; TGFb and Th3 and Tregs
14
Q
What are hte features of hte mucosal barrier in food hypersensitivity?
A
increased antigen load; increased permeability of hte gut wall; DC presentation and stimualtion of Th2 cells
15
Q
What is the effect of IL-5?
A
eosinophil activation
16
Q
What are hte features of food allergy?
A
itching; hives; rhinorrhea; wheezing; angioedema; anaphylaxis-circulatory collapse
17
Q
What are the features of gastrointestinal hypersensitivity?
A
N&V&D; stomach pain
18
Q
How is food allergy diagnosed?
A
skin prick testing; RAST; food challenges
19
Q
What is RAST?
A
radioallergosorbent test- detects the presence of IgE antibodies to a particular allergen
20
Q
What is the gold standard of food allergy diagnosis?
A
double-blind placebo controlled food challenges
21
Q
What are hte atopic diseases?
A
asthma; hay-fever; food allergy; eczema; atopic dermatitis
22
Q
What is the risk of atopic disease if both parents have different atopic syndromes?
A
58%
23
Q
What is the risk of atopic disease if both parents have the same clinical disease?
A
78%
24
Q
What is the association of HLA with atopy?
A
DR4 and/orDR7 alleles are seen in 42% of patients vs 2% of health subjects
25
What supports the hygiene hypothesis?
studies showing less allergy in less economically devleoped countries; lack of early exposure to diret and germs in Western coutnires; loss of tolerance to food proteins
26
What are the features of timing of oral exposure to foods that may impact oral tolerance?
age at weaning; different quantities; breastfeeding
27
What is the recommended timing weaning?
introduction to solids after exlcusive breastfeeding at 4-6 months
28
What is the mx of urticaria?
histamine
29
What is hte MOA of sodium cromoglycate?
staibilises mast cells
30
What is the mx of anaphylaxis?
adrenaline; b2 agonists; o2; fluids; antihistamines; steroids; glucagon
31
What demonstrates the food allergy has increase in the past 10-15 years?
peanut allergy has increased two fold in children
32
How are food-specific IgE levels related to food allergy?
many individuals have detectable food-specific IgE but no clinical allergy, but increasing concentrations of specific IgE increases risk of clinical allergy
33
What is associated with food allergy severity?
reduced platelet activating factor acetylhydrolases- unable to inactivate PAF; target organ sensitivity
34
Give an exmaple of where target organ sensitivity affects allergy severity?
people with asthma are at higher risk of severe or fatal anaphylaxis
35
What demonstrates that food allergy is genetically determined?
peanut allergy is 10x as likely in a child with a sibling who is peanut allergic
36
What is oral allergy syndrome?
oral tolerance is bypassed because sensitisation happens through respiratory route e.g birch pollen protein may result in allergy with raw apples due to cross-reactivity
37
What mice models demonstrate the nonoral exposure to stable proteins invokes allergy?
epicutaneous application of food proteins may result in sensitisation leading to systemic allergy following oral exosure
38
What human data suggests that skin exposure may be sensitising?
peanut allergy was associated with the use of infant skin creams containing peanut oil-6.8 OR
39
What is the function of enzymes; bile salts and extremes of pH in oral tolerance?
combine to make allergens less immunogenic
40
What suggests that low pH is important in oral tolerance?
infants have a higher gastric pH which may reduce the efficiency of hte infant mucosal barrier- food allergy is more common in infants; antacid mediations increase the risk of sensitisation to ingested foods
41
What is the function of Th3 cells?
CD4 cells which secrete TGFb
42
Why are intestinal epithelial cells thought to play an important role in oral tolerance?
can process luminal antigen and present it to T cells on MHC-II but lack second signal thereby inducing tolerance
43
What suggests that the gut microbiotia is important in oral tolerance?
mice raised in a germ free environment fail to develop normal tolerance; if treated with antibiotics or lack TLR4- more prone to developing peanut allergy
44
What suggests that Tregs are important in oral tolerance?
in IPEX syndrome where there is mutation in FOXP3- syndrome includes severe food allergies and atopic dermatitis
45
Why is there Th2 direction in allergic immune reponse?
murine models demonstrate that DCs direct T cells towards a Th2 profile at the time of antigen presentation in the gut
46
How is the cooking of allergens related to allergy induction?
peanut consumption is nearly equivalent in US and China wwhereas in US much higher rates of allergy; US roast peanuts whereas in China they boil or fry- roasting increases stability and allergenicity of the peanuts
47
Where is the current direction in treatment of allergy?
immunotherapy
48
What have been the results with peanut allergy subcut immunotherapy?
resulted in modest clinical improvement but significant adverse effects including recurrent anaphylacis
49
What are the approaches to improving immunotherapy for allergy?
change the route of administration eg sublingual or modifying hte treatment proteins
50
What have been the efficacy of reponse with oral immunotherapy for egg and milk allergy in children?
70-80%
51
What is the difference between desensitisation and tolerance?
desensitisation- allergen is ingested without symptoms dyuring treatment but has to be ingested daily vs tolerance where food may be ingested without allergy symptoms despite periods of abstinnce
52
What is the function of engineered proteins in immuntherapy?
identify IgE binding sites on proteins and mutate the sites to ablate IgE binding whilst preserving the proteins ability to stimualte T cells
53
How would peptide immunotherapy work?
create a vaccine composed of numerous small peptides that span the sequence of native allergenic proteins which presents T cell epitopes but avoids crosslinking of IgE
54
How may combination strategies in immunotherapy be used?
use of anti-IgE antibodies to quell allergic reactions to immuntherapy
55
What causes a failure to digest lactose?
low lactase activty in the small intestinal brush border - hypolactasia
56
What age group have high lactase?
neonates
57
What is the normal level of lactase in adults?
lactase non-persistance
58
Which ethnic groups have lactase persistence?
most but not all Northern Europeans
59
What happens when there is lactose malabsorption?
lactose breaks down in the colon by microbes resulting in hydrogen; carbon dioxide and lactate
60
How is lactose intolerance diagnosed?
history or lactose-H2 breath test
61
What is the lactose-hydrogen breath test?
after oral lactose there is high hydrogen in the breath
62
What is lactose broken down into in the small intestine by lactase?
glucose/galactose
63
Give an example of a polymorphism that results in persistance/non-persistance of lactase?
trans polymorphism upstream of lactase start site in Finnish population- Enattah
64
When was milk tolerance thought to begin?
in the Middle East 11,000 years ago with the start of agriculture and domestication of dairy animals which spread to central europe by 7,500 years ago lactase persistence emerged in central europe
65
What are the symptoms of fructose and sorbitol malabsorption?
abdo pain and diarrhoea following fruit juices or diet drinks
66
What causes the symptoms of fructose/sorbitol malabsorption?
small intestinal malabsorption of these monosacchrarides results in metabolism in the colon
67
How is frcutose/sorbitol malabsorption diagnosed?
history and breat hydrogen afer ingestion
68
Why are fermented dairy drinks more popular in the middle east?
reflects lactase non-persistence
69
What is the result of oligosaccharide ingestion?
they are prebiotics which result in growth of good bacteria
70
What are polysaccharides broadly known as?
fiber
71
What is the result of fiber ingestion?
bulking effect and increased transit through the gut
72
What are FODMAPs?
fermentable oligo; di- and mono-sacchradies and polyols
73
What are the common physiologic effects of FODMAPs?
increase water retention in the small intestine via osmotic effects; rapid fermentation by intestinal bacteria leading to release of gas and short-chain farry acids- pain and bloating and abnormal motility
74
What is typically seen on duodenal histology with coeliac disease?
subtotal villous atrophy with crypt hyperplasia
75
What should be avodied in a gluten free diet?
no wheat; barley or rye products
76
What is the definition of coeliac disease?
inflamamtory disease of upper small intestine resulting from gluten ingestion in genetically susceptible individuals
77
What is the prevalence of coealic disease?
1 in 100
78
Why may coealic patients have clotting problems ?
vitamin K malabsorption
79
What are hte frequent symptoms of coelaic disease?
fatigue; steatorrhea/diarrhoea; weight loss; anameia
80
Who first described coeliac disease in children?
Gee in 1888
81
What is the avergae age of diagnosis of coeliac disease?
>50
82
What is the gold standard of diagnosis of coeliac disease?
intestinal biopsy
83
What is refractory coeliac disease?
symptoms and villous atrophy on strict GFD >1 year
84
What is typically seen with potential CD?
parents with coeliac disease, positive bloods but normal biopsy
85
When were endomysial antibodies first desribed?
1983 by Chorzelski
86
How are endomysial antibodies detected?
indirect immunofluoresnce on monkey oesophagus
87
What type of antibody are endomysial natibody?
IgA- IgG if selective IGA deficiency
88
What is the specific and sensitivity of endomysial antibodies?
99% specificity and 95% sensitivity
89
What is the autoantigen recognised by endomysial antibodies?
tissue transglutaminase
90
What is the result of ingestion of gluten ?
leads to generation of harmful gluten peptides which in predisposed individuals can induce adaptive and innate immune repones
91
What HLA groups does coeliac disease almost exclusively occur in?
HLA-DQ2 and/or HLA-DQ8 haplotypes
92
What suggests taht there are other genetic and/or environmental factors in disease onset aside from DQ2/DQ8?
only a fraction of individuals with that haplotypes ingesting gluten develop coealic disease
93
Which gender is coelaic disease more common in?
females
94
How has prevalence of coeliac disease been changing over time?
appears that according to seroprevalence that over 20 years there has been 2-fold increase, which has been confimred by recent metanalyses in biopsy-proven coeliac disease
95
What are the potential environmental factors in coeliac disease?
consumption of gluten containing cereals; infection in the early years of life and lower economic status; inferior hygienic environment
96
What is gluten made up of ?
a complex mixutre of alcohol-soluble gliadins and alcohol-insoluble glutenins
97
Whiat amino acids are gliadins and glutenins rich in?
proline and glutamine
98
What is the result of the proline rich content of gluten?
proteins are fairly resistance to proteolytic processsing by gastric, pancreatic and brush-border enzymes
99
What is the function of transglutaminase?
converts glutamine residues in gluten peptides to glutamic acid in a deamidation reaction
100
What is the result of deamidation of glutamine?
enhances the binding of gluten peptides by increasing their affinity to HLA-DQ2 on APCs
101
How much of the genetic risk are HLA-DQ2 and HLA-DQ8 thought to account for?
25-40%
102
What is the carrier frequency of HLADQ2 nad DQ8?
around 40%
103
What are the alleles that encode for HLA-DQ2?
HLADQA1*05:01 and HLADQB1*02:01
104
What is HLA-DQ8 encoded for by?
HLADQA1*03 and HLADQB1*03:02
105
How many patinets carry HLA-DQ2?
90%, and almost all the reslt carry HLA-DQ8
106
What is the adaptive immune response in coeliac disease characterised by?
mucosal gluten-specific CD4 T cells ; antibodies towards wheat gliadin and enzyme TG2
107
How do gluten peptides access the lamina propria?
actively through the transepithelial route of passively by paracellular flux caused by comrpomised petihlial barrier function (GI infection is associated with coeliac, some genetic disposition to poorly functioning tight junctions?)
108
What may explain why only some individuals with HLA-DQ2/DQ8 develop coeliac disease?
TCRs are generated in a ranom process so high-affinity TCRs specific for gliadin may be produced in a minority of those patients
109
Which cytokiens do activated gluten speicifc CD4 T cells produce?
IFNy and IL-21
110
What are hte innate immune responses in coeliac disease characterised by?
increased mucosal expression of IL-15; IL-18 and type I IfNs which are produced by stressed intestinal epithelial cells or DCs
111
What is the function of IL-15 in coeliac disease?
inhibits Tregs promoting loss of oral tolerance and immune regulation and by licenses IELs to kill intestinal epithelial cells
112
What is the function of IELs?
a heterogeneous population of T cells that patrol the mucosal barrier and exert effector functions without antigen-specific priming- interact with intestinal epithelial cells and can induce apoptosis when required
113
What suggests that microoragnisms are invovled in the development of coeliac disease?
specific microbiota species assocaited with coeliac disease; GI infections increase the risk of developing coeliac diseae
114
What suggested a role for early-life feeding practices in coeliac disease ?
in the Swedish epidermic, when dietary gluten introduction was postponed, with infant food gluten content increased
115
What happens to tissue transaminase IgA antibodies with GFD?
decrease but if rechallenged increase back up
116
What is dermatits herpetiformis?
vesicular; pruritic rash affecting particularly the arms and shoulders asssociated with villous atrophy and gluten sensitivity
117
What is seen on skin biopsy with dermatitis herpetiformis?
granular IgA deposits
118
What are the metabolic complications of coeliac disease?
nutrient malabosprtion and impaired nutriotnal status; osteoporosis;
119
What are hte neoplastic complications of coeliac disease?
enteropathy-associated T cell lymphoma; adenocarcinoma
120
What happens to calcium and bone mineral density wiht GFD?
reduced calcium absorption returns to normal with 1 year of GFD; with improvemnt in BMD
121
What is the difference in progonsis between coeliacs and other patients for primary small bowel malignancy?
surivial at 30 months if 52% overall but 13% in coeliacs
122
What is the commonest cause of malabsorption?
coeliac disease
123
How is coeliac histology in the small intestine graded?
Marsh grading
124
How are tissue transglutaminase antibodies measured ?
ELISA
125
What is the function of tissue transglutaminase ?
cross-links glutamine residues in gliadin creating neoantigens, by deamindating glutamine to glutamate
126
What is the specific polypeptide identified in coeliac disease?
33-mer peptide of a2-gliadin
127
What causes the enteropathy in CD?
inflammatory damage and apoptosis
128
What causes the histological changes in CD?
enterocyte apoptosis results in villous atrophy and stimulated regeneration results in hyperplastic cyrpts
129
What happens to the apoptotic score when a GFD is started?
reduces - Moss
130
How many immunogenic epitopes does the 33-mer carry?
multiple copies of three eptiopes
131
What is the rate of coeliac disease in first degree relatives?
1 in 10
132
What is the evidence for silent disease?
>30% of dermatitis herpetiformis have no GI symtpoms; population screening- prevalence of undiagnosed cases is aroudn 10x that os previously disgnoased
133
What are the features of sero-positive patients in the Cambridge Gp health study?
lighter, good/excellent health, less likely to smoke, lower cholesterol, Hbl increased risk of osteoporosis and mild anaemia
134
What indicates that there is something predisposing girls to coeliac disease more than sex-hormone determined phenotype?
in children aged 7, there is an increased prevlance in girls - x2
135
What groups have a higher prevalence of coeliac disease?
T1DM; thyroid disease; addison's ; osteoporosis; anaemia blood donors; IBS; turners; downs
136
What is the MZ concordance of coeliac disease?
aroudn 80%
137
What is the frequence of HLA-DR3 in Northern European patients?
65-95%
138
What HLA group is more common in mediterranaean patietns?
DR5/DR7
139
How may patients with coeliac disease who are DR3 or DR5/DR7 heterozygous express the same HLA-DQ molecule?
in DR3 individuals the 2 genes (has 2 chains) are on the same chromosome whereas in DR5/7 they are located in trans
140
What DR allele is associated with DQ8?
DR4
141
What is the concordance for coeliac disease in HLA-matched siblings and what does this indicate?
aroudn 30%- other genes must account for inheritability (MZ twins is 80%)
142
What diseases are polymorphisms in the CTLA4 exon associated with?
IDDM; Grave's; coeliac--Hunt
143
What gene in the MHC region which is non-HLA is associated with coeliac disease?
MICA- Spanish (involved in IELs and apotosis)
144
Variants in what cytokine regions are associated with coeliac disease?
IL2 and IL21
145
What is the function of IL-21?
enhances B, T, NK cell proliferation and IFNy production- greatly increased in untreated coalic dseiase
146
Why is there thought to a reduction in IL2 in untreated Coeliac disase?
in NOD mouse IL2 influences Treg activity determines susceptibility to AI diseases
147
How many non-HLA coeliac disease associated regions are there?
8
148
What are the 8 non-HLA associated regions with coelaic disease identified in GWAS coding for?
cytokines; chemokine receptor signalling; receptors; proteins invovled in immune activation
149
What is the function of IL-18?
induces T cells to synthesis IFNy
150
How many of the regions associated with coealic disease overlap with T1DM?
4/9
151
What genes did further GWAS follow-ups identify?
genes involved in the NFkB pathway
152
What do the new 8 variants explain in terms of heritability?
<5%
153
What is the relationship of a long noncoding RNA near IL18 receptor assocaited protein with coeliac disease?
increases susceptibility as influences IL18RAP expressed and causes increased inflammation
154
What did a study in Denver with risk HLA haplotypes determine about the timing of gluten introduction and development of CD?
if introduced before (5 fold increase) or after 4-6 month period- increased risk --Norris
155
How was rotavirus infection associated with coeliac disease?
1 rotavrisu infection increased risk, whilst >2 infections increased risk even further
156
What is thought to be the reason that rotavirus would increase susceptibility to coealic disease?
allows gluten through the intestine and the creation of antibodies
157
What have further studies after the Denver study found?
intervention studies have not backed up the associations found in the Denver study with weaning
158
How does IFNy produced by stimulated CD4+ T cells contribute to mucosal damage in coeliac disease?
stimulates FasL expression on IEL CD8+ cells and MMP expressiong by fibroblasts both leading to enterocyte destruction
159
Why do people who have been ingesting gluten all their lives start to develop coeliac disease?
may be due to infection/ inflammation that increases permability of hte mucosal barrier allowing gluten entry to the subepithelial region, with increased release of tTG in response to inflammation or mechnical stress
