hypersensitivity, allergy and inflammation

Question 1

3 most common sources of allergens (proteins causing allergy)

Answer 1

proteins from house dust mites, grass and tree pollens, cat and dog

Question 2

prevalence of atopy in young adults in UK

Answer 2

50%

Question 3

3 severities of allergy

Answer 3

mild occasional symptoms, severe chronic asthma, life threatening anaphylaxis

Question 4

genetic risk factors of allergy: % with family history and whether monogenic or polygenic

Answer 4

80% of atopics have family history, with polygenic traits

Question 5

genetic risk factors of allergy: what genes are linked to raised IgE, asthma, atopy and eczema

Answer 5

chromosome 5 IL-4 gene cluster (also containts IL-5 and IL-13), chromosome 11q IgE receptor, structural cells (filaggrin, IL-33)

Question 6

6 environmental risk factors of allergy

Answer 6

age (increases from infancy, peaks in teens, reduces in adulthood), gender (asthma common in male children but female adults), family size (more common in small families), infections (early life infections protect), animals (early exposure protects), diet (breast feeding, anti-oxidants, fatty acids protect)

Question 7

are allergies increasing in UK and why

Answer 7

yes and fast, so due to environmental changes

Question 8

types of inflammation in allergy: 3 diseases most common due to type I hypersensitivity (IgE mediated)

Answer 8

anaphylaxis, urticaria, angioedema

Question 9

types of inflammation in allergy: disease most common due to type II hypersensitivity (IgG antibody mediated)

Answer 9

idiopathic/chronic urticaria

Question 10

types of inflammation in allergy: 3 diseases most common due to mixture of type I hypersensitivity (IgE mediated) and type IV hypersensitivity (chronic inflammation T cell mediated)

Answer 10

asthma, rhinitis, eczema

Question 11

what 2 things does expression of allergic disease require, and when they occur

Answer 11

development of sensitisation to allergens instead of tolerance (primary response - usually in early life), and further allergen exposure to produce disease (memory response - any time after sensitisation)

Question 12

sensitisation in atopic airway disease

Answer 12

allergen -> APC -> CD4+ -> Th1/Treg/Th2 -> if Th2, activate B cells to produce IgE by interleukin signalling

Question 13

subsequent exposure in atopic airway disease

Answer 13

allergen -> APC -> memory Th2 -> activate B cells by interleukin signalling to produce IgE which then bind to mast cells, and activation of eosinophils

Question 14

eosinophils: prevalence, location, recruitment, production, contents and outcome of activation

Answer 14

0-5% of blood leukocytes; present in blood, most reside in tissues (epithelia and submucosa); recruited during allergic inflammation; generated from bone marrow; nucleus has two lobes and it contains large granules with toxic proteins; lead to tissue damage

Question 15

mast cells: location, cell surface receptors

Answer 15

reside in tissue and have IgE receptors on cell surface

Question 16

mast cells: what does crosslinking of IgEs lead to

Answer 16

mediator release of pre-formed histamine, cytokines and toxic proteins from granules; newly synthesised leukotrienes and prostaglandins

Question 17

neutrophils: 3 occasions when important in allergy

Answer 17

virus induced asthma, severe asthma, atopic eczema

Question 18

neutrophils: prevalence, contents

Answer 18

55-70% blood leukocytes, with polymorphic nuclei (several lobes) and contain digestive enzymes in granules

Question 19

neutrophils: 3 things they synthesise when activated

Answer 19

oxidant radicals, cytokines, leukotrienes

Question 20

what causes acute inflammation of airways in asthma

Answer 20

mast cell activation and degranulation by pre-stored mediators (e.g. histamine) and newly synthesied mediators (e.g. prostaglandins, leukotrienes), causing acute airway narrowing

Question 21

2 mechanisms by which mediators released by mast cells cause acute airway narrowing in asthma

Answer 21

smooth muscle contraction, vascular leakage

Question 22

describe 2 phase response to single allergen challenge

Answer 22

immediate early response to inhaled allergen by IgE (type I hypersensitivity), followed by late response caused by cellular response 5hrs later (type IV hypersensitivity)

Question 23

what 5 things cause chronic inflammaiton of aiways in asthma

Answer 23

cellular infiltrate (Th2, eosinophils), smooth muscle hypertrophy, mucus plugging, epithelial shedding, sub-epithelial fibrosis

Question 24

9 important clinical features of asthma

Answer 24

reversible generalised airway obstruction (leads to chronic episodic wheeze), bronchial hyperresponsiveness (leads to bronchial irritability), cough, mucus production, breathlessness, chest tightness, response to treatment, spontaneous variation, reduced and variable peak flow (PEF)

Question 25

PEF in a typical day for someone with poorly controlled asthma

Answer 25

always below 100%: wheezy when wake up due to exposure of allergens overnight -> feel fine -> if exercise, rapid decrease -> spontaneous reductions throughout day; multiple uses of reliever inhaler

Question 26

cause of seasonal allergic rhinitis

Answer 26

hay fever (grass, tree pollens)

Question 27

2 causes of perennial allergic rhinitis

Answer 27

house dust mite, pets

Question 28

4 symptoms of allergic rhinitis

Answer 28

sneezing; rhinorrhoea; itchy nose and eyes; nasal blockage, sinusitis and loss of smell/taste

Question 29

2 features and cause of allergic eczema

Answer 29

chronic itchy skin rash; flexures of arms and legs; caused by house dust mite senstisation and dry cracked skin (fillagrin)

Question 30

what complicates allergic eczema

Answer 30

bacterial and viral infections

Question 31

clearance of allergic eczema in life

Answer 31

50% by 7 y/o, 90% by adult

Question 32

common infancy-3 years food allergies

Answer 32

egg, cows milk

Question 33

common children/adults food allergies

Answer 33

peanut, nut, shell fish, fruit, cereal, soya

Question 34

3 mild symptoms of food allergies

Answer 34

itchy lips and mouth, angioedema, urticaria

Question 35

6 severe symptoms of food allergies

Answer 35

nausea, abdominal pain, diarrhoea, collapse, wheeze, anaphylaxis

Question 36

define anaphylaxis

Answer 36

severe generalised allergic reaction which is uncommon but potentially fatal

Question 37

cause of anaphylaxis

Answer 37

generalised degranulation of IgE sensitised mast cells

Question 38

6 symptoms of anaphylaxis

Answer 38

itchiness around mouth, pharynx, lips; swelling of lips, throat and other parts of body; wheeze, chest tightness, dyspnoea; faintness, collapse; diarrhoea and vomiting; death if severe and untreated

Question 39

effect of anaphylaxis on cardiovascular system

Answer 39

vasodilation, cardiovascular collapse

Question 40

effect of anaphylaxis on respiratory system

Answer 40

bronchospasm, laryngeal oedema

Question 41

effect of anaphylaxis on skin

Answer 41

vasodilation, erythema, urticaria, angioedema

Question 42

effect of anaphylaxis on GI system

Answer 42

vomiting, diarrhoea