allergic disease Flashcards
what is an allergy?
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
what are types I, II and III?
antibody mediated
what is type IV?
mediated by cells
what is the relationship between response time and type?
the response time increases as you go along the types
what is type I?
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
what is type II?
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
what is type III?
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.
what is type IV?
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
what is contact dermatitis?
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
why do we get allergies?
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
what is the relation between immune response to parasitic disease and hypersensitivity?
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
what is the hygiene hypothesis?
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.
what is the mechanism for the hygiene hypothesis?
th1/2 deviation, lack of antigenic competition and immune regulation - allergies are th2 response type
what does polygenic diseases mean in relation to allergic response?
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
there are susceptibility genes for allergic disease, what are these?
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.
what triad of diseases are allergies associated with?
atopic dermatitis, asthma and allergic rhinitis
how does an allergy develop?
there is barrier dysfunction - inherently defective meaning the allergen can enter, sensitise the immune system and drive the differentiation of T cells
what is the role of IgE in the conventional immune response?
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
what do innocuous antigens do in allergic response?
they drive an IgE mediated response
what does the first encounter to antigen result in?
innate and IgM response
how are B cells stimulated in IgE production?
IgE presents allergen to B and Th2 cells. It is recognised and Th2 releases IL4 to stimulate the B cell to proliferate
how can barrier function be disrupted?
due to genetic defect or inflammation
what is early priming?
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.
what does the B cell differentiate into and why?
plasma cells and mainly IgE antibodies - this is because it recognises the antigen / allergen
what causes the immune reaction?
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
what is the IgE mediated allergic response?
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.
what is anaphylaxis?
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.
what are the symptoms of the atopic triad?
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
what is asthma and what does the initial and late response cause?
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.
what are the symptoms and treatments for allergic rhinitis?
the symptoms are conjunctivitis related and the main treatment is anti-histamines and intranasal steroids
what is the difference between allergic and non allergic rhinitis?
allergic: seasonal (pollen or moulds), perennial (house dust mite or animal dander)
non-allergic: vasomotor, structure and infective, drugs hormonal or polyps
what are other symptoms of allergic rhinitis?
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
in dermatitis what is external and internal?
eczema - internal
contact - external
what is dermatitis?
itching, blistering and flaking of skin
what types of dermatitis are there?
discoid eczema, photosensitive and seborrhoeic dermatitis and irritant contact dermatitis
what is the barrier problem interplay?
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
what does the differentiation and clonal expansion of Th2 cells lead to?
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
how does the immediate response of the type I occur?
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
what happens in the late phase response of type I?
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
where is local IgE not seen?
not seen in allergic skin inflammation due to lack of eosinophils in skin
what does Th1 do?
produces interferon and tumour necrosis factor - activation and apoptosis of keratinocytes, bronchial epithelial cells and pulmonary smooth muscle cells
how would you diagnose an allergy?
history, certain IgE, basophil activation test, skin prick test, intradermal test and graded challenge test
what is intradermal testing used for and why?
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
what are some false negatives of common allergy tests?
could be antigens stuck to cells and not in blood so not picked up
taking anthistamines
what are the reason for some false positives?
in eczema and asthma IgE levels are high anyway
sensitive skin
what are positives for specific IgE testing?
safe as take out of patient and externally see in blood
what are the positives of the skin prick test ?
it is quick and there is patient satisfaction
what is the treatment for allergic disease?
mostly symptomatic - antihistamines, steroids and adrenaline - immunotherapy will stop from having a severe attack
when might you use immunotherapy rather than symptomatic treatment?
life threatening reactions to wasp and bee stings
severe hay fever
animal dander allergy
when would you not use immunotherapy?
when there are multiple allergies, food allergies, eczema or spontaneous urticaria
what is SIT and what is it associated with?
SIT is allergen specific immunotherapy. It is associated with decreased immediate and late phase allergic inflammation and improved tolerance in the allergen challenge
what are the benefits of SIT?
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
how does SIT work?
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.
what are the adverse reactions to food?
dairy - more common in children
nuts - more common in adults
water soluble glycoproteins
what are the clinical manifestations of food allergy?
respiratory (rhinitis and bronchospasm), GI (vomiting, diarrhoea and oral) and cutaneous (urticaria, angiodema, atopic dermatitis)
what would you need to know in drug reaction history?
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
how would you manage a drug allergy?
desenitisation, graded challenge and intradermal testing if appropriate
what can cause all four types of reaction?
penicillin
what is the basis of desensitisation?
small, diluted dose so slowly release mediators and is not a large reaction
how do you know when someone is clear of an allergy?
they are challenged and tolerate it
