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Path - Immuno > Allergy > Flashcards

Allergy Flashcards

1
Q

immunological process that results in immediate and reproducible symptoms after exposure to an allergen is an?

A

allergic disorder

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2
Q

what is an Allergen?

A

a harmless substance that can trigger an IgE mediated immune response (often type 1 hypersensitivity reaction)

and may result in clinical symptoms

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3
Q

______ is the detection of specific IgE either by skin prick testing or in vitro blood tests

: OCCURS _____THAN ALLERGIC DISEASE

A

Sensitisation

MORE OFTEN

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4
Q

Characterise the immune response to;

Allergens + Helminthes, Venoms

A

immune response is by Th2 cells

targeted towards tissue damage they cause

rather than direct recognition of the pathogen as with bacteria, viruses and fungi

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5
Q

Characterise the immune response to;

bacteria, viruses and fungi

A

Th1, Th17 immune response

based off recognition of the pathogen - via PAMP

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6
Q

what is the sensor of infection with;

allergens, venoms and worms? which triggers a Th2 immune response

A

Stressed or Damaged

Epithelium

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7
Q

which cytokines are involved in signalling in allergy? these are released by?

which are the effector cytokines? these are released by?

A 
Released by damaged epithelium;
GM-CSF
IL-25
IL-33
*TSLP -Thymic stromal lymphopoeitin 
effector cytokines;
Released by Th9 cells,ILC2 (type 2 innate lymphoid cells) & Th2 Cells:
*IL-5
*IL-4
 IL-9
 *IL-13

released by Tfh2 cells;
IL4, IL21

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8
Q

which are the effector cells in Th2 immune responses?

what is each of their role?

which produces IgE?

A
  1. Eosinophils - allergen and womr expulsion
  2. Mucosa - mucus secretion
  3. B cells - IgE and IgG4
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9
Q

what is the sensor which triggers Th2 immune MEMORY response?

A

Mast cell in tissues

Cross linking IgE

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10
Q

in a Th2 immune MEMORY response, which are the signalling and effector cytokines and proteins?

A

*Histamine
Prostaglandins
*Leukotrienes
Proteases

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11
Q

which signalling and effector cytokines and proteins are drug targets in allergy?

A
  • Histamine

* Leukotrienes

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12
Q

what are the effector cells in Th2 immune memory responses ?

what is the end effect/immune response?

A

Endothelium
Smooth muscle
Neuron

response;
Worm & allergen expulsion
Enhanced epithelial barrier function

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13
Q

which cytokines Helps B cells to produce IgE ?

A

iL-4

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14
Q

which cytokines Expands and activate eosinophils ?

A

iL-5

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15
Q

which cytokines Stimulate mucous secretion ?

A

iL-13

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16
Q

which th subset has Signature cytokine; IL-4, IL-5, IL-13

A

CD4 th2

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17
Q

lineage determining transcription factor and the signal transduction protein of the CD4 Th2 cell?

A

lineage determining transcription factor GATA-3

signal transduction protein STAT-6
Signal- S, transduction - T

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18
Q

what is the MOA of eosinophils?

A

Eliminate pathogens by secretion of cytotoxic granules, RNAase proteins and extracellular traps

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19
Q

what is Implicated in late stage tissue damage in atopic dermatitis, asthma, eosinophilic oesophagitis, and granulomatous disease ?

A

EOSINOPHILS!

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20
Q

What is the MOA of IgE?

A

IgE binds to high affinity receptor (Fc3R1) on mast cells, basophils, eosinophils and DC

IgE induces mast and basophil degranulation associated with immediate hypersensitivity (allergic) reactions

IgE also binds to ‘low affinity’ (Fc3R2) receptor on above cells as well as B cells, respiratory and gastrointestinal epithelial cells

IgE function
Protection against helminth and parasitic infection

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21
Q

how does IgE interact with B cells, respiratory and gastrointestinal epithelial cells?

A

binds to ‘low affinity’ (Fc3R2) recepto

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22
Q

What are the 2 mast cell subtypes?

A

Tryptase T - skin

(Chymotryptase CT) - airways

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23
Q

2 mechanisms of mast cell degranulation?

A

1) IgE/IgG receptors which respond to antibody-antigen cross linking
2) G-protein-coupled receptors which are ligands for soluble mediators

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24
Q

2 mechanisms of mast cell degranulation?

A

1) IgE/IgG receptors which respond to antibody-antigen cross linking
2) G-protein-coupled receptors which are ligands for soluble mediators

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25
Q

list the key mast cell receptors to which tthe following bind to;

(IgE)
(IgG)
(opiates, quinolones)

A

FcR3R1 - 3 for IgE

FcgR1 and FcgR1IA - f for IgG

MRGPRX2

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26
Q

Cross linking of bound IgE by antigen results in which 3 reactions?

A

Release of pre-formed inflammatory mediators from granules (histamine)

Release and synthesis of lipid mediators (leukotrienes, prostaglandins)

Synthesis of pro-inflammatory cytokines

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27
Q

Mast cell degranulation leads to which 3 responses?

A

Recruitment of soluble proteins and inflammatory cells to site of infection

Increase in rate of lymphatic flow back to regional lymph nodes

Smooth muscle contraction in lungs and gut (may help to expel pathogens)

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28
Q

What factors promote IgE production ?

A

Antigen dose

Length of exposure

Physical properties of allergen
i.e. heat resistance

Route of exposure

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29
Q

____ exposure promotes immune tolerance whereas ____ and ____ induces IgE sensitisation

A

tolerance - Oral (o for oral)

sensitisation - skin and respiratory (s for skin)

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30
Q

Defects in skin epithelial barrier (atopic dermatitis) are caused by?

A

filagrin mutation

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31
Q

which mutation is implicated in many allergic diseases eg allergic rhinitis?

A

filagrin mutation

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32
Q

Stressed or damage epithelial cells secrete IL-25, IL-33, GM-CSF and TSLP which act on __________________________

and neurons to induce Th2 cells immune responses (IL-4, IL-5, IL-9, IL-13)

A

tissue immune cells (DC, basophils, type 2 innate lymphoid cells)

33
Q

_____ plays a crucial role in development of Th2 immune responses and is only induced following peptide-MHC presentation to naïve/memory Th2 cells

A

IL-4 ;

Helps B cells to produce IgE

34
Q

Rapid onset of symptoms within 2-3 hours are caused by which reactions?

A

allergen cross linking of IgE on surface of mast cells and basophils

which causes inflammatory mediator release -> histamine leukotriene, prostaglandin

35
Q

Delayed symptoms are caused by which reactions?

A

T2 cell immune responses
(IL-4, IL-5, IL-13 -> B cell, eosinophil, mucus)

eosinophil related tissue damage

36
Q

IgE degranulation of mast cells promotes a ___ clinical response

A

early/immediate

37
Q

allergic rhinitis is aka?

A

hay fever

38
Q

Why have allergic disorders risen over the last 150 years? list 4 theories?

A

Hygiene hypothesis:

Increase childhood vaccination and exposure to broad spectrum antibiotics

Alteration in intestinal microbiome

Dietary factors: more processing

39
Q

list 2 theories for rise in allergic rhinitis?

A

change in farming practices - rye grass ( generate more pollen). more grass pollen

hygeine hypothesis

40
Q

list 2 theories for rise in Childhood asthma?

A

kids indoors more - react to outdoor allergens

hygeine hypoth

vaccines and BS Abx

41
Q

why do amish communities see protection from dust asthma unlike Hutterites?

A

lipopolysaccharides LPS in amish dust samples

more TNF and IL-1 (pro inflam cytokines) in amish exposed to this dust

cause suppression of allergic inflammation

42
Q

roast peanut promotes__ whereas boiled ___

A

roast - IgE

boiled - igg

43
Q

what is the the key to diagnosis in allergic disease?

A

history

44
Q

list some Allergen specific IgE (Sensitisation) Tests?

A

Skin prick and intradermal test

IgE blood tests

45
Q

Asthma (HDM, pets) and Allergic rhinitis (HDM, grass, tree pollens) have onset when?

A

childhood

46
Q

Atopic dermatitis and Food allergy (milk, egg, nuts) have onset when?

A

infancy

47
Q

which allergies have onset in adulthood?

A

Drug allergy
Bee allergy
Oral allergy syndrome- itchiness in their mouth and throat, sometimes with mild swelling

Occupational allergy

48
Q

which allergic response Occurs within minutes or up to 3 hours after exposure to allergen?

A

igE

49
Q

symptoms of IgE allergic responses?

A

At least 2 organ systems are usually involved.*

Skin: angioedema (swelling of lips, tongues, eyelids) etc

Respiratory tract: cough, SOB wheeze, etc

Gastrointestinal tract: nausea, vomiting and diarrhoea

Blood vessels and Brain: symptoms of hypotension (faint, dizzy, blackout) and a sense of impending doom

50
Q

Allergic symptoms may be triggered by cofactors such as?

A

cofactors such as exercise, alcohol, NSAID and in children viral infection

51
Q

Results of skin prick test or serum specific IgE do not predict ___________?

A

the severity of reaction

52
Q

A positive test is indicated by _____ ?

A

a wheal ≥ 3mm greater than the negative control (diluent).

53
Q

what must be done 2 days before skin prick test?

A

Antihistamines and some anti-depressants should be discontinued for at least 48 hours beforehand

54
Q

which test is More sensitive but less specific than Skin prick test?

A

intradermal test

55
Q

what are the indcations of an intradermal test?

risks?

A

Best used to follow up negative venom and drug allergy test (better than blood tests)

greater risks of anaphylaxis

56
Q

what do specific IgE (antibody) blood tests/blood sensitisation tests involve?

A

Anti-IgE with label injected. binds to igE on allergen

57
Q

what are the downsides to specific IgE blood tests ?

A

higher affinity bonding associated with risk

Detection of IgE is necessary but not sufficient to make a diagnosis of allergic disease

extract can casue symptoms

high concentrations -> symptoms

58
Q

skin prick tests can t be used in __?

A

in patients with dermato-graphism or extensive eczema

59
Q

Indications for blood sensitisation tests?

A

in patients with dermato-graphism or extensive eczema

No access to SPT and/or IDermal Test

Patients who can’t stop anti-histamines

Patient with a history of anaphylaxis

etc

60
Q

which is the Test for IgE sensitisation against individual protein within whole allergen extract

A

Component resolved /molecular allergen testing

61
Q

which components in nuts cause a severe reaction?

A

Storage proteins (2 s albumins)

62
Q

in wheat what is a better marker of specific wheat allergy than total wheat IgE?

A

Omega-5-gliadin

63
Q

Failure of which biomarker to return to baseline 6-12rhs after anaphylaxis may be indicative of systemic mastocytosis

A

MAST CELL TRYPTASE

64
Q

in Basophil activation tests, Activated basophils increase the expression of ______ proteins on cell surface

A

CD63, CD203, CD300 proteins

65
Q

what is the Gold standard for food and drug allergy diagnosis ?

A

Gold standard for the diagnosis of food allergy is a

double blind oral food challenge.

66
Q

case;

a woman gets hypotension + rash during anaesthesia. its not clear if it is anaphylaxis.

best test to diagnose anaphylaxis?

A

MAST CELL TRYPTASE

67
Q

A 15 year old with a history of asthma and hayfever who notices an urticarial and angioedema skin rash shortly after eating peanuts.

What is the most appropriate initial diagnostic test?

A

skin prick test - very fast

68
Q

non immune reactions which include metabolic, pharmacological and unknown mechanisms is known as?

A

food intolerance

69
Q

Non IgE mediated (coeliac disease) food allergies are examples of ?

A

type 4 hypersensitivity

70
Q

which allergies can and cant be outgrown

A

can - milk, egg

can’t - peanut, tree nut

71
Q

most common allergies in young kids vs adults?

A

kids - 1.milk, 2.egg

adults - 1.shellfish, 2.peanut

72
Q

what allergen component causes reactions in shellfish?

A

Tropomyosin

73
Q

A positive skin test or food specific IgE blood test indicates ____ but not necessarily ____

A

indicates sensitisation but not necessarily allergy

74
Q

according to guidelines, how to manage food allergy?

A
  1. Avoidance
  2. Emergency management - epipens
  3. Prevention
    - eg Breast feeding:
    - early rather than delayed introduction of peanut
75
Q

which Common food triggers are implicated in Food associated exercise induced anaphylaxis

A

wheat, shellfish, celery

76
Q

Delayed food-induced anaphylaxis to beef, pork, lamb

is caused by igE antibody to ___?

A

IgE antibody to oligosaccharide alpha-gal (α1, 3-galactose) found in gut bacteria

77
Q

what causes oral allergy syndrome?

A

Sensitisation to inhalant pollen protein lead to cross reactive IgE to food

Onset after pollen allergy established: affect adults > young children

Respiratory exposure to pollen (birch) results in IgE directed to homologous proteins in stone fruits (apple, pear) vegetables (carrot) and nuts (peanut, hazelnut)

no rxn when these foods are cooked - heat labile antigens

78
Q

A 35 year old man with tree pollen hayfever and immediate lip tingling and swelling immediately after eating apples.

What is the most likely explanation for IgE hypersensitivity ?

A

Cross reactive IgE sensitisation between hay fever and apple allergens

  • > oral symptoms only
  • > prior pollen allergy

Path - Immuno (11 decks)

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