Allergy Flashcards by RK Splendid

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

allergic disorder

How well did you know this?

Not at all

Perfectly

what is an Allergen?

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

and may result in clinical symptoms

How well did you know this?

Not at all

Perfectly

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

: OCCURS _____THAN ALLERGIC DISEASE

Sensitisation

MORE OFTEN

How well did you know this?

Not at all

Perfectly

Characterise the immune response to;

Allergens + Helminthes, Venoms

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

How well did you know this?

Not at all

Perfectly

Characterise the immune response to;

bacteria, viruses and fungi

Th1, Th17 immune response

based off recognition of the pathogen - via PAMP

How well did you know this?

Not at all

Perfectly

what is the sensor of infection with;

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

Stressed or Damaged

Epithelium

How well did you know this?

Not at all

Perfectly

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

which are the effector cytokines? these are released by?

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) &amp; Th2 Cells:
*IL-5
*IL-4
 IL-9
 *IL-13

released by Tfh2 cells;
IL4, IL21

How well did you know this?

Not at all

Perfectly

which are the effector cells in Th2 immune responses?

what is each of their role?

which produces IgE?

Eosinophils - allergen and womr expulsion
Mucosa - mucus secretion
B cells - IgE and IgG4

How well did you know this?

Not at all

Perfectly

what is the sensor which triggers Th2 immune MEMORY response?

Mast cell in tissues

Cross linking IgE

How well did you know this?

Not at all

Perfectly

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

*Histamine
Prostaglandins
*Leukotrienes
Proteases

How well did you know this?

Not at all

Perfectly

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

Histamine

* Leukotrienes

How well did you know this?

Not at all

Perfectly

what are the effector cells in Th2 immune memory responses ?

what is the end effect/immune response?

Endothelium
Smooth muscle
Neuron

response;
Worm & allergen expulsion
Enhanced epithelial barrier function

How well did you know this?

Not at all

Perfectly

which cytokines Helps B cells to produce IgE ?

iL-4

How well did you know this?

Not at all

Perfectly

which cytokines Expands and activate eosinophils ?

iL-5

How well did you know this?

Not at all

Perfectly

which cytokines Stimulate mucous secretion ?

iL-13

How well did you know this?

Not at all

Perfectly

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

CD4 th2

How well did you know this?

Not at all

Perfectly

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

lineage determining transcription factor GATA-3

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

How well did you know this?

Not at all

Perfectly

what is the MOA of eosinophils?

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

How well did you know this?

Not at all

Perfectly

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

EOSINOPHILS!

How well did you know this?

Not at all

Perfectly

What is the MOA of IgE?

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

How well did you know this?

Not at all

Perfectly

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

binds to ‘low affinity’ (Fc3R2) recepto

How well did you know this?

Not at all

Perfectly

What are the 2 mast cell subtypes?

Tryptase T - skin

(Chymotryptase CT) - airways

How well did you know this?

Not at all

Perfectly

2 mechanisms of mast cell degranulation?

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

How well did you know this?

Not at all

Perfectly

2 mechanisms of mast cell degranulation?

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

How well did you know this?

Not at all

Perfectly

list the key mast cell receptors to which tthe following bind to; (IgE) (IgG) (opiates, quinolones)

FcR3R1 - 3 for IgE FcgR1 and FcgR1IA - f for IgG MRGPRX2

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

Release of pre-formed inflammatory mediators from granules (histamine) Release and synthesis of lipid mediators (leukotrienes, prostaglandins) Synthesis of pro-inflammatory cytokines

Mast cell degranulation leads to which 3 responses?

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)

What factors promote IgE production ?

Antigen dose Length of exposure Physical properties of allergen i.e. heat resistance Route of exposure

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

tolerance - Oral (o for oral) sensitisation - skin and respiratory (s for skin)

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

filagrin mutation

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

filagrin mutation

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)

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

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

IL-4 ; Helps B cells to produce IgE

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

allergen cross linking of IgE on surface of mast cells and basophils which causes inflammatory mediator release -> histamine leukotriene, prostaglandin

Delayed symptoms are caused by which reactions?

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

IgE degranulation of mast cells promotes a ___ clinical response

early/immediate

allergic rhinitis is aka?

hay fever

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

Hygiene hypothesis: Increase childhood vaccination and exposure to broad spectrum antibiotics Alteration in intestinal microbiome Dietary factors: more processing

list 2 theories for rise in allergic rhinitis?

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

list 2 theories for rise in Childhood asthma?

kids indoors more - react to outdoor allergens hygeine hypoth vaccines and BS Abx

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

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

roast peanut promotes__ whereas boiled ___

roast - IgE boiled - igg

what is the the key to diagnosis in allergic disease?

history

list some Allergen specific IgE (Sensitisation) Tests?

Skin prick and intradermal test | IgE blood tests

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

childhood

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

infancy

which allergies have onset in adulthood?

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

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

igE

symptoms of IgE allergic responses?

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

Allergic symptoms may be triggered by cofactors such as?

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

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

the severity of reaction

A positive test is indicated by _____ ?

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

what must be done 2 days before skin prick test?

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

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

intradermal test

what are the indcations of an intradermal test? risks?

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

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

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

what are the downsides to specific IgE blood tests ?

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

skin prick tests can t be used in __?

in patients with dermato-graphism or extensive eczema

Indications for blood sensitisation tests?

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

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

Component resolved /molecular allergen testing

which components in nuts cause a severe reaction?

Storage proteins (2 s albumins)

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

Omega-5-gliadin

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

MAST CELL TRYPTASE

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

CD63, CD203, CD300 proteins

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

Gold standard for the diagnosis of food allergy is a double blind oral food challenge.

case; a woman gets hypotension + rash during anaesthesia. its not clear if it is anaphylaxis. best test to diagnose anaphylaxis?

MAST CELL TRYPTASE

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?

skin prick test - very fast

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

food intolerance

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

type 4 hypersensitivity

which allergies can and cant be outgrown

can - milk, egg can't - peanut, tree nut

most common allergies in young kids vs adults?

kids - 1.milk, 2.egg adults - 1.shellfish, 2.peanut

what allergen component causes reactions in shellfish?

Tropomyosin

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

indicates sensitisation but not necessarily allergy

according to guidelines, how to manage food allergy?

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

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

wheat, shellfish, celery

Delayed food-induced anaphylaxis to beef, pork, lamb | is caused by igE antibody to ___?

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

what causes oral allergy syndrome?

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

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 ?

Cross reactive IgE sensitisation between hay fever and apple allergens - > oral symptoms only - > prior pollen allergy