allergic disease

Question 1

what is an allergy?

Answer 1

it is an undesirable, damaging, discomfort-producing and sometimes fatal response produced by the normal immune system, directed against innocuous antigens in a pre-sensitised host - substances that are normally considered harmless

Question 2

what are types I, II and III?

Answer 2

antibody mediated

Question 3

what is type IV?

Answer 3

mediated by cells

Question 4

what is the relationship between response time and type?

Answer 4

the response time increases as you go along the types

Question 5

what is type I?

Answer 5

it is anaphylactic - mediated by IgE to an exogenous antigen. It takes 15-30 minutes with a wheal and flare response to things such as pollen. It is associated with allergic asthma, and the increase in baso and eosinophils

Question 6

what is type II?

Answer 6

it is cytotoxic. It is when IgG and IgM react against a combined self and foreign antigen at the cell surface - results in complement activation, phagocytosis and ADCC. the onset is from minutes to hours and it resutls in cell lysis and necrosis. the common antigen is penicillin and is associated with erythroblastosis fetalis and goodpasture’s nephritis

Question 7

what is type III?

Answer 7

immune complex. It is when IgG and IgM act against a soluble antigen resulting in an immune complex deposition. The onset is 3-8hours with vasculitis. The presentation is erythema, oedema and necrosis. The traditional cause is serum sickness from an active immunisation and it is associated with SLE. there will be a rise in complement and neutrophils.

Question 8

what is type IV?

Answer 8

delayed - the onset is 48-72 hours with erythema induration. It is an antigen specific T cell mediated cytotoxicity. The common cause is nickel/metals and tuberculin. It is associated with contact dermatitis, eczema, and secretion of cytokines and chemokines that cause damage. There will be raised monocytes and lymphocytes

Question 9

what is contact dermatitis?

Answer 9

it is a condition associated with type IV delayed hypersensitivity reaction. It is when the incomplete antigen gets access to the immune system and there is a cellular response in the lymph nodes

Question 10

why do we get allergies?

Answer 10

those components of the immune system that are involved in allergic response are primarily involved in responses to parasitic infection. Parasites are large compared to bacteria and therefore there is a large immune response. The body has evolved to give a rapid tissue based response to reinfection and lack of infectious drive is a contributory factor in allergic disease

Question 11

what is the relation between immune response to parasitic disease and hypersensitivity?

Answer 11

cross reactive and same components seen in both. There is a total increase in the levels of IgE that are specific to antigen, there is the presence of CD4+ T cells that secrete IL4, IL5, and IL13 and there is tissue inflammation with basophil infiltration, eosinophilia, and mastocytosis

Question 12

what is the hygiene hypothesis?

Answer 12

epidemiological data shows an increase in allergies. If the immune system is not fighting bacteria it will turn to fight harmless antigens. Microbes stimulate the immune system to prevent allergies, reduction in infection burden is associated with increased allergies, therefore pathogen free environment means more allergies. After anti-parasitics there will be more allergies.

Question 13

what is the mechanism for the hygiene hypothesis?

Answer 13

th1/2 deviation, lack of antigenic competition and immune regulation - allergies are th2 response type

Question 14

what does polygenic diseases mean in relation to allergic response?

Answer 14

there are a number of genes that are involved in that allergic response
cytokine gene cluster IL3,5,9,13
IL12R and IL4R
FceRI
IFNg, TNF
these alone are not sufficient for disease only for susceptibility

Question 15

there are susceptibility genes for allergic disease, what are these?

Answer 15

group 1: sense the environment. They encode molecules that directly modulate the effect of an environmental risk factor on allergic disease
group 2: barrier function. High proportion of those genes involved in susceptibility to allergic disease are in the epithelium.

Question 16

what triad of diseases are allergies associated with?

Answer 16

atopic dermatitis, asthma and allergic rhinitis

Question 17

how does an allergy develop?

Answer 17

there is barrier dysfunction - inherently defective meaning the allergen can enter, sensitise the immune system and drive the differentiation of T cells

Question 18

what is the role of IgE in the conventional immune response?

Answer 18

antigen requires processing. it will present to T cells and therefore result in cytokine release and the delineation of T helper subsets into different types

Question 19

what do innocuous antigens do in allergic response?

Answer 19

they drive an IgE mediated response

Question 20

what does the first encounter to antigen result in?

Answer 20

innate and IgM response

Question 21

how are B cells stimulated in IgE production?

Answer 21

IgE presents allergen to B and Th2 cells. It is recognised and Th2 releases IL4 to stimulate the B cell to proliferate

Question 22

how can barrier function be disrupted?

Answer 22

due to genetic defect or inflammation

Question 23

what is early priming?

Answer 23

allergen enters system through disrupted barrier and goes to the regional lymph nodes. The APC presents it to a T cell which then differentiated into different kinds depending on cytokines released.

Question 24

what does the B cell differentiate into and why?

Answer 24

plasma cells and mainly IgE antibodies - this is because it recognises the antigen / allergen

Question 25

what causes the immune reaction?

Answer 25

the IgE ABs attach to the mast cell and allergen cross links the ABs which causes the mast cell to release it’s cell contents - degranulation

Question 26

what is the IgE mediated allergic response?

Answer 26

it is the IgE mediated mast cell and basophil degranulation, resulting in the release of preformed and de novo synthesised inflammatory mediators such as histamine. The initial response is wheal and flare with an onset of 15-30 minutes, and the later phase response is eosinophils, leukotrienes and prostaglandins and Th2 cells.

Question 27

what is anaphylaxis?

Answer 27

it is a serious allergic response with a clear drop in BP after exposure to known allergen and airway symptoms. there is urticaria and angiodema. Watch breathing, airways and consciousness.

Question 28

what are the symptoms of the atopic triad?

Answer 28

if you treat one of allergic rhinitis, asthma and eczema then there will be poor control, there is wheezing, cough, airway restriction and night time awakening

Question 29

what is asthma and what does the initial and late response cause?

Answer 29

it is a disease of inflammation and hyper-reactivity of the small airways. The main stimulus in childhood is house dust mite or aero-allergic stimuli. The initial symptoms are IgE mediated and the damage to the airways is through the late phase response. This causes the airways to be hyper reactive to non-allergic stimuli.

Question 30

what are the symptoms and treatments for allergic rhinitis?

Answer 30

the symptoms are conjunctivitis related and the main treatment is anti-histamines and intranasal steroids

Question 31

what is the difference between allergic and non allergic rhinitis?

Answer 31

allergic: seasonal (pollen or moulds), perennial (house dust mite or animal dander)
non-allergic: vasomotor, structure and infective, drugs hormonal or polyps

Question 32

what are other symptoms of allergic rhinitis?

Answer 32

nasal congestion (mucus, polyps, oedema), tonsillar or adenoidial enlargement, loss of nasopharyngeal area, obstructive sleep apnoea, airway inflammation (oedema or mucus), airway constriction and hyperreactivity

Question 33

in dermatitis what is external and internal?

Answer 33

eczema - internal

contact - external

Question 34

what is dermatitis?

Answer 34

itching, blistering and flaking of skin

Question 35

what types of dermatitis are there?

Answer 35

discoid eczema, photosensitive and seborrhoeic dermatitis and irritant contact dermatitis

Question 36

what is the barrier problem interplay?

Answer 36

when there is disruption to the barrier the allergen gets in and stimulates Th2 - this then eventually leads to pruritus which then disrupts the barrier - cycle

Question 37

what does the differentiation and clonal expansion of Th2 cells lead to?

Answer 37

the production of cytokines - IL4 and IL13 leading to the immunoglobulin class switching to IgE and clonal expansion of naive and IgE memory B cell populations. IL4 also helps T cell differentiation into Th2 cells and there is more antigen presentation

Question 38

how does the immediate response of the type I occur?

Answer 38

there is the crosslinking of the mast cell and basophil cell surface FcRI (high affinity IgE receptor). IgE bound allergens lead to the production of vasoactive amines (histamine), lipid mediators (prostaglandins and leukotrienes), chemokines and cytokines

Question 39

what happens in the late phase response of type I?

Answer 39

the allergen specific T cells migrate to site of allergen exposure under the influence of cyto and chemokines and clonally expand, and dendritic cells and local IgE increase T cell activation. There is activation of mast cells and basophils for release of histamine chemokines and cytokines

Question 40

where is local IgE not seen?

Answer 40

not seen in allergic skin inflammation due to lack of eosinophils in skin

Question 41

what does Th1 do?

Answer 41

produces interferon and tumour necrosis factor - activation and apoptosis of keratinocytes, bronchial epithelial cells and pulmonary smooth muscle cells

Question 42

how would you diagnose an allergy?

Answer 42

history, certain IgE, basophil activation test, skin prick test, intradermal test and graded challenge test

Question 43

what is intradermal testing used for and why?

Answer 43

for drug allergy testing as more sensitivity is needed - inject tiny amount into skin and note size after around 15 minutes - if over 3mm then positive

Question 44

what are some false negatives of common allergy tests?

Answer 44

could be antigens stuck to cells and not in blood so not picked up
taking anthistamines

Question 45

what are the reason for some false positives?

Answer 45

in eczema and asthma IgE levels are high anyway

sensitive skin

Question 46

what are positives for specific IgE testing?

Answer 46

safe as take out of patient and externally see in blood

Question 47

what are the positives of the skin prick test ?

Answer 47

it is quick and there is patient satisfaction

Question 48

what is the treatment for allergic disease?

Answer 48

mostly symptomatic - antihistamines, steroids and adrenaline - immunotherapy will stop from having a severe attack

Question 49

when might you use immunotherapy rather than symptomatic treatment?

Answer 49

life threatening reactions to wasp and bee stings
severe hay fever
animal dander allergy

Question 50

when would you not use immunotherapy?

Answer 50

when there are multiple allergies, food allergies, eczema or spontaneous urticaria

Question 51

what is SIT and what is it associated with?

Answer 51

SIT is allergen specific immunotherapy. It is associated with decreased immediate and late phase allergic inflammation and improved tolerance in the allergen challenge

Question 52

what are the benefits of SIT?

Answer 52

it prevents the development of sensitisation to new allergens and will slow the progression of allergic rhinitis to asthma. There is a duration of effect beyond the treatment time and it modifies both cellular and humoral responses to allergens

Question 53

how does SIT work?

Answer 53

the ratio of Th1:Th2 is increased, and there is the induction of Tr cells. IL10 from monocytes, B, T cells and macrophages also increases. IL10 with the expression of TGF increases the function of Tr cells and immunoglobulin class switching meaning that there is less antigen capture. Finally it reduces the number of mast cells so there is less mediator release and the recruitment of eosinophils and neutrophils is reduced.

Question 54

what are the adverse reactions to food?

Answer 54

dairy - more common in children
nuts - more common in adults
water soluble glycoproteins

Question 55

what are the clinical manifestations of food allergy?

Answer 55

respiratory (rhinitis and bronchospasm), GI (vomiting, diarrhoea and oral) and cutaneous (urticaria, angiodema, atopic dermatitis)

Question 56

what would you need to know in drug reaction history?

Answer 56

indication for drug and detailed description of reaction, time between taking and onset, number of doses taken and awareness of pharmacological and non-immunological ADR

Question 57

how would you manage a drug allergy?

Answer 57

desenitisation, graded challenge and intradermal testing if appropriate

Question 58

what can cause all four types of reaction?

Answer 58

penicillin

Question 59

what is the basis of desensitisation?

Answer 59

small, diluted dose so slowly release mediators and is not a large reaction

Question 60

how do you know when someone is clear of an allergy?

Answer 60

they are challenged and tolerate it