Allergy Flashcards
What is meant by allergic and hypersensitive reactions?
Undesirable, damaging and sometimes fatal reactions produced by the normal immune system - key factor is its directed against an innocuous antigens in a pre-sensitized host
Which hypersensitivity reactions are Ab mediated and which are cell mediated?
Types 1-3 = Ab mediated
Type 4 = Cell mediated
Type 3 hypersensitivity reactions are also referred to as what?
Immune complex reactions
Type 2 hypersensitivity reactions are also referred to as what?
Cytotoxic reactions
Type 4 hypersensitivity reactions are also referred to as what?
Delayed type
Which type of hypersensitivity reaction is the classic allergic reaction?
Type 1
Type 1 hypersensitivity reactions are mediated by which type of Ab?
IgE
Types 2 and 3 hypersensitivity reactions are mediated which types of Ab?
IgG and IgM
What is the immunopathogenesis of a Type 2 Hypersensitivity reaction?
1) IgM/IgG Ab response against combined self/foreign Ag at the cell surface
2) When Ab binds to Ag on solid surface get complement activation and activation of phagocytic cells, ADCC (Ab dependent cellular cytotoxicity)
What are the clinical features of Type 2 cytotoxic reactions?
1) Onset is minutes to hours
2) Cell lysis and necrosis
What is a common antigen causing a Type 2 cytotoxic reaction?
Penicillin
Give 2 diseases associated with Type 2 cytotoxic reactions?
1) Eryhtroblastosis fetalis (Rhesus reaction)
2) Goodpasture’s nephritis
What roughly happens in the rhesus reaction?
Rhesus negative mother - exposed to Rh+ child on first pregnancy and develops antigens - sensitisation
On second pregnancy with Rh+ baby - Abs bind to Ag and get cell lysis
What is the immunopathology of Type 3 hypersensitivity reaction?
IgG/IgM Ab against soluble antigens - immune complex deposition
What are the clinical features of a Type 3 hypersensitivity reaction?
1) Onset 3-8 hours
2) Vasculitis
Type 3 hypersensitivity reactions are the traditional cause of what?
Serum-sickness
Which disease is associated with Type 3 hypersensitivity reaction?
SLE
When the route of entry of antigen is intravenous in a type 3 hypersensitivity reaction what are the 3 resulting diseases and 3 sites of immune complex deposition?
Diseases 1) Vasculitis 2) Nephritis 3) Arthritis Site of deposition 1) Blood vessel walls 2) Renal glomeruli 3) Joint spaces
When the route of entry of antigen is subcutaneous in a type 3 hypersensitivity reaction what is the resulting disease and site of immune complex deposition?
Disease - Arthus reaction
Site - Perivascular area
When the route of entry of antigen is inhaled in a type 3 hypersensitivity reaction what is the resulting disease and side of immune complex deposition?
Disease - Farmer’s lung
Site - Alveolar/Capillary interface
What is the key difference between a Type 2 and 3 hypersensitivity reaction?
Type 2 - Ab against Ag attached to a cell surface so cell lysis
Type 3 - Ab against soluble Ag so immune complex deposition
What is the immunopathology of Type 4 (delayed type) hypersensitivity reaction?
- Ag specific T-cell mediated cytotoxicity
Exposure to Ag, develop T cell which can recognise that Ag
On re-exposure T cells cause tissue damage by release of various mediators
What are the clinical features of a Type 4 hypersensitivity reaction?
1) Delayed onset
2) Erythema induration
Give 1 common Ag in a type hypersensitivity reaction?
Metals eg. nickel
The tuberculin reaction is an example of what kind of hypersensitivity reaction?
Type 4
Give a disease associated with Type 4 hypersensitivity?
Contact dermatitis
What are the 5 key steps in the development of allergy (Type 1 hypersensitivity)?
1) Barrier dysfunction - allowing entry of Ag
2) Sensitisation
3) Changes in T cell sub-sets dominated by Th2
4) IgE Ab produced
5) Allergic symptoms
Which 6 organs are commonly involved in allergic reactions?
1) Eyes - allergic conjunctivitis
2) Nose - allergic rhinitis
3) Mouth - oral allergy syndrome
4) Airways - allergic asthma
5) Skin - atopic dermatitis
6) GI tract - food allergy
What is the link between parasitic infection and allergies?
Those components of the immune system involved in responses to parasitic infection are also involved in allergic responses
The system has developed to produce a rapid tissue-based response to re-infection
What are the main 3 components of immune response to parasitic disease?
1) Increased levels of IgE - total and specific to pathogen
2) Tissue inflammation with eosinophilia and mastocytosis and basophil infiltration
3) Presence of CD4+ cells secreting IL4,IL5 and IL13
What is the general principle of the ‘hygiene hypothesis’ in relation to increased allergies?
Infections seem to have some affect on developing atopic conditions and autoimmune disorders in animal models
Th1 response is thought to be towards management of infections, Th2 response directs towards allergies
Simplistic theory is that if you don’t have the competition from infectious agents, allergens and the Th2 response predominate - in line with the Th2 deviation seen in atopic conditions
What is the genetic influence of the allergic immune response?
Polygenic disease
Genetic factors alone are not sufficient for the disease, only increase susceptibility
Need the environmental factors
What 5 areas can you have genetic defects in leading to increased susceptibility to allergic disease?
1) Environment sensing - ie being hypersensitive
2) Atopic immune response
3) Defects in barrier function so allergens can get in
4) Tissue response - may have an inappropriate response
5) Eosinophils
Has asthma, atopic dermatitis or rhinitis been show to be associated with more genetic defects?
Atopic dermatitis is associated with the most defects followed by asthma, followed by rhinitis
What is meant by allergens?
Antigens that initiate an IgE mediated response
What is key in hypersensitive reactions in terms of exposure to Ag?
Can only have a hypersensitive reaction on re-exposure to an allergen to which you have previously been exposed ie. sensitised
In allergic reactions what response does the first encounter with an allergen result in?
Innate and IgM response
What is the immune process in an IgE allergic response (Type 1 hypersensitivity)?
1) Exposure to Ag which is presented to T cells by APCs
2) T cell cytokine release resulting in Th2 delineation and B cell activation to produce IgE
3) IgE Fc portion binds to mast cell IgE receptors
4) On re-exposure allergen binds to Fac portion of mast cell bound IgE
5) Cross linking causes release of mediators from mast cells and basophils leading to symptoms
What 6 cells/organs are affected by the pre-formed mediators released by mast cells/basophils in an allergic reaction?
1) Smooth muscle
2) Blood vessels
3) Platelets
4) Mucous glands
5) Sensory nerve endings
6) Eosinophils
T cells can differentiate into what 4 types - what does each roughly do?
1) Th1 - fights infections
2) Th2 - allergic reactions
3) Th17 - fights infection
4) Treg - suppresses all other types
Which cytokine released by Th2 cells is important in leading to the production of IgE by B cells?
IL-4
What 3 steps are considered to be the early priming events in allergic reactions?
1) Defect in epithelial barrier
2) Allergen taken up actively or passively
3) Allergens processed by APCs and activate T cells
What is the clinical features of IgE mediated allergic response?
1) Fast onset (15-30 mins)
2) Wheal and flare
Which 2 types of cell are heavily involved in the late phase response of an allergic reaction?
1) Eosinophils
2) Th2 cells
Which is the commonest pre-formed mediator released by mast cells causing the immediate response in allergic reactions?
Histamine
Secondary mediators playing a role in the late phase reaction of allergic response are produced by what pathway in the mast cell, what are the main 2?
Produced via the arachidonic acid pathway
Leukotrienes and prostaglandins are the main 2
What are the 3 main roles of Th2 T cells in allergic reactions?
1) Multiple cytokines released
2) Activates innate inflammatory response
3) Drives immunoglobulin production by B cells
What 3 conditions make up the atopic triad, what kind of hypersensitivity reaction is associated with each?
1) Asthma - Type 1
2) Rhinitis - Type 1
3) Eczema - Type 4
What is the main difference between immunopathology in rhinitis and asthma?
1) Rhinitis = type 1 reaction in nasal mucosa (upper airways)
2) Asthma = type 1 reaction in alveolar epithelium (lower airways)
What are the 2 types of rhinitis?
1) Allergic
2) Non-allergic
What determines whether allergic rhinitis is perennial or seasonal?
When the allergens are present eg.
Host mite - perennial
Pollen - seasonal
What are the main 3 symptoms of rhinitis?
1) Blocked nose
2) Runny nose
3) Often eye symptoms
What are 3 common allergens causing rhinitis?
1) House mite
2) Animal danders
3) Pollens
What are the 2 main treatments of rhinitis?
1) Anti-histamines
2) Nasal steroids
What are the common allergens in childhood asthma?
Aero-allergic stimuli
House dust mite thought to have a key role
Is damage to airways in asthma caused by the immediate or late phase response?
Late phase response
What is the main problem with damaged airways in asthma?
They are hyper-reactive to non-allergic stimuli eg. fumes
Immediate symptoms in asthma are mediated by what?
IgE Ab
Which 2 substances released by mast cells in the late phase reaction are key in asthma?
Leukotrienes and Prostaglandins
What are the 3 types of dermatitis?
1) Atopic - eczema
2) Allergic - type 4 hypersensitivity
3) Non-allergic
How does dermatitis of all types present clinically?
1) Intense itching
2) blistering/weeping
3) cracking of skin
What is thought to be a major trigger in atopic dermatitis?
House dust mite
What is the treatment of atopic dermatitis?
Topical steroids and moisturisers
What is the mechanism thought to be the reasons for itching in atopic dermatitis?
1) Activated T cells release a cytokine called IL31 - T cell itch mediator
2) Directly causes a scratch which leads to a cycle of barrier disruption and further exposure to hapten
What is anaphylaxis?
An acute, potentially life threatening IgE mediated systemic hypersensitivity reaction
What are the GI, respiratory, CV and neurological symptoms in severe anaphylaxis?
GI - Profuse diarrhoea, loss of bowel control
Respiratory - Severe wheezing, cyanosis, resp. arrest
CV - Hypotension, bradychardia, collapse, cardiac arrest
Neurological - Confusion, loss of consciousness
What is the gold standard test in diagnosis of allergy?
Oral challenge test
What 7 tests/procedures can be used in the diagnosis of allergy?
1) History
2) Specific IgE
3) Skin prick test
4) Intra-dermal test
5) Oral challenge test
6) Basophil activation test
7) Component resolved diagnostics
What is the principle of the basophil activation test?
Mix patients blood with allergen
Upon cross linking basophils upregulate the expression of specific activation markers which can be detected
What is the 1 advantage and disadvantage of the specific IgE test over the skin prick test?
Ad - safe
Disad - false positives and negatives
What are the 2 advantages and disadvantages of the skin prick test over the specific IgE test?
Ad - quick and patient satisfaction (they have seen it themselves)
Disad - false positives and negatives, slight risk
What are the 3 symptomatic treatments of allergic reactions?
1) Antihistamines
2) Steroids
3) Adrenaline
What are the 3 indications for specific immunotherapy (sublingual or subcutaneous) in allergy?
1) Life threatening reactions to wasp and bee sting
2) Severe hay fever
3) Animal dander allergy
In which 3 situations is specific immunotherapy for allergy not useful?
1) Multiple allergies
2) Food allergies
3) Allergic rashes - eczema, urticarial
What is the main principle of immunotherapy for allergy?
Trick the immune system to tolerate the antigen through controlled exposure
Switch from Th2 to Th1 response
What are the 6 major food allergens?
1) Cow’s milk
2) Egg
3) Legumes (peanut, soybean, tree nuts)
4) Fish
5) Crustaceans/Molluscs
6) Cereal grains
What are the 4 common clinical manifestations of adverse reactions to food?
1) GI - vomiting diarrhoea, oral symptoms
2) Respiratory - rhinitis and bronchospasm
3) Cutaneous - urticarial, angioedema
4) Anaphylaxis
What are the 4 clinical manifestations of IgE mediated reactions to drugs?
1) Urticaria
2) Angioedema
3) Bronchospasm
4) Anaphylaxis
