hypersensitivity, allergy and inflammation Flashcards
allergy: summarise the factors underlying the development of atopic/allergic diseases, listing the important clinical features of asthma, hay fever, allergic eczema and anaphylaxis
3 most common sources of allergens (proteins causing allergy)
proteins from house dust mites, grass and tree pollens, cat and dog
prevalence of atopy in young adults in UK
50%
3 severities of allergy
mild occasional symptoms, severe chronic asthma, life threatening anaphylaxis
genetic risk factors of allergy: % with family history and whether monogenic or polygenic
80% of atopics have family history, with polygenic traits
genetic risk factors of allergy: what genes are linked to raised IgE, asthma, atopy and eczema
chromosome 5 IL-4 gene cluster (also containts IL-5 and IL-13), chromosome 11q IgE receptor, structural cells (filaggrin, IL-33)
6 environmental risk factors of allergy
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)
are allergies increasing in UK and why
yes and fast, so due to environmental changes
types of inflammation in allergy: 3 diseases most common due to type I hypersensitivity (IgE mediated)
anaphylaxis, urticaria, angioedema
types of inflammation in allergy: disease most common due to type II hypersensitivity (IgG antibody mediated)
idiopathic/chronic urticaria
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)
asthma, rhinitis, eczema
what 2 things does expression of allergic disease require, and when they occur
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)
sensitisation in atopic airway disease
allergen -> APC -> CD4+ -> Th1/Treg/Th2 -> if Th2, activate B cells to produce IgE by interleukin signalling
subsequent exposure in atopic airway disease
allergen -> APC -> memory Th2 -> activate B cells by interleukin signalling to produce IgE which then bind to mast cells, and activation of eosinophils
eosinophils: prevalence, location, recruitment, production, contents and outcome of activation
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
mast cells: location, cell surface receptors
reside in tissue and have IgE receptors on cell surface
mast cells: what does crosslinking of IgEs lead to
mediator release of pre-formed histamine, cytokines and toxic proteins from granules; newly synthesised leukotrienes and prostaglandins
neutrophils: 3 occasions when important in allergy
virus induced asthma, severe asthma, atopic eczema
neutrophils: prevalence, contents
55-70% blood leukocytes, with polymorphic nuclei (several lobes) and contain digestive enzymes in granules
neutrophils: 3 things they synthesise when activated
oxidant radicals, cytokines, leukotrienes
what causes acute inflammation of airways in asthma
mast cell activation and degranulation by pre-stored mediators (e.g. histamine) and newly synthesied mediators (e.g. prostaglandins, leukotrienes), causing acute airway narrowing
2 mechanisms by which mediators released by mast cells cause acute airway narrowing in asthma
smooth muscle contraction, vascular leakage
describe 2 phase response to single allergen challenge
immediate early response to inhaled allergen by IgE (type I hypersensitivity), followed by late response caused by cellular response 5hrs later (type IV hypersensitivity)
what 5 things cause chronic inflammaiton of aiways in asthma
cellular infiltrate (Th2, eosinophils), smooth muscle hypertrophy, mucus plugging, epithelial shedding, sub-epithelial fibrosis
9 important clinical features of asthma
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)
PEF in a typical day for someone with poorly controlled asthma
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
cause of seasonal allergic rhinitis
hay fever (grass, tree pollens)
2 causes of perennial allergic rhinitis
house dust mite, pets
4 symptoms of allergic rhinitis
sneezing; rhinorrhoea; itchy nose and eyes; nasal blockage, sinusitis and loss of smell/taste
2 features and cause of allergic eczema
chronic itchy skin rash; flexures of arms and legs; caused by house dust mite senstisation and dry cracked skin (fillagrin)
what complicates allergic eczema
bacterial and viral infections
clearance of allergic eczema in life
50% by 7 y/o, 90% by adult
common infancy-3 years food allergies
egg, cows milk
common children/adults food allergies
peanut, nut, shell fish, fruit, cereal, soya
3 mild symptoms of food allergies
itchy lips and mouth, angioedema, urticaria
6 severe symptoms of food allergies
nausea, abdominal pain, diarrhoea, collapse, wheeze, anaphylaxis
define anaphylaxis
severe generalised allergic reaction which is uncommon but potentially fatal
cause of anaphylaxis
generalised degranulation of IgE sensitised mast cells
6 symptoms of anaphylaxis
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
effect of anaphylaxis on cardiovascular system
vasodilation, cardiovascular collapse
effect of anaphylaxis on respiratory system
bronchospasm, laryngeal oedema
effect of anaphylaxis on skin
vasodilation, erythema, urticaria, angioedema
effect of anaphylaxis on GI system
vomiting, diarrhoea