Flashcards in Week 4 allergy Deck (77)
What is the definition of Allergy & Hypersensitivity?
Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitized (immune) host.
Which hypersensitivity reactions are Ab mediated and which are cell mediated?
Types 1-3 = Ab mediated Type 4 = Cell mediated
What type of antibody and antigen causes type 1 hypersensitivity?
What is the response time and appearance of type 1 hypersensitivity?
15- 30 minutes reponse time
Appearance --> weal and flare
what is the histology of type 1 hypersensitivity? How is it transfered?
basophils & eosinophil
Antibodies is by how it gets transfered
What is another name for type 2 hypersensitivity?
what is another name for type 3 hypersensitivity?
What is the Immunopathogenesis of type 2?
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
Cause cell damage
What are the clinical features of type 2? Include the histology invovled in type 2
Onset minutes to hours
Cell lysis and necrosis
The histology --> antibody and
What is a common antigen that causes type 2?
What are associated diseases with type 2 hypersensitivity?
What is Rhesus?
Rhesus (Rh) factor is an inherited protein found on the surface of red blood cells. If your blood has the protein, you're Rh positive. If your blood lacks the protein, you're Rh negative.
What is the immunopathalogy of type 3?
IgG/IgM Ab against soluble antigen- immune complex deposition
Clinical features of type 3?
Histology --> complement and
How is type 1,2,3 trasnfered?
What sickness does type 3 hypersensitivity cause?
Traditional cause-serum sickness
What is the assoicted disease with type 3?
In type 3 hypersensitivity if the antigen entered the body via IV what would be the resulting disease and the site of immune complex deposition?
Diseases 1) Vasculitis 2) Nephritis 3) Arthritis Site of deposition
1) Blood vessel walls 2) Renal glomeruli 3) Joint spaces
In type 3 hypersensitivity if the antigen entered the body via subcutaneous route what would be the resulting disease and the site of immune complex deposition?
Disease - Arthus reaction
Site - Perivascular area
In type 3 hypersensitivity if the antigen entered the body via inhalation what would be the resulting disease and the site of immune complex
Disease - Farmer's lung Site - Alveolar/Capillary interface
What is the difference beteen type 2 and type 3 in the interaction between antigens and antibodies?
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 immunopathalogy of type 4?
Antigen specific T-cell mediated cytotoxicity
what is the clinical features of type 4?
Delayed onset 48-72h
Apearance Erythema induration
What is Erythema?
It is superficial reddening of the skin, usually in patches, as a result of injury or irritation causing dilatation of the blood capillaries.
Common antigen of type 4?
Metals-e.g nickel --> cheap metals
What is Tuberculin reaction?
Tuberculin is an extract of Mycobacterium tuberculosis that is used in skin testing in animals and humans to identify a tuberculosis infection
Assoicated disease with type 4?
What is the process that causes type 1 hypersensitivity?
1) Barrier dysfunction - allowing entry of Ag
3) Changes in T cell sub-sets dominated by Th2
4) IgE Ab produced
5) Allergic symptoms
What contributes to a person developing allergic disease?
The lack of infectious drive is a contributory factor in allergic disease
What are the 6 common organs invovled in allergic reaction.
Give example for each of the organs of allergic reaction
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
Why do we get 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 is the immune response to parasitic disease?
Increased levels of IgE
Specific to pathogen – cross-reactive
Tissue inflammation with:
eosinophilia & mastocytosis
Presence of CD4+ T cells secreting:
IL4, IL5 & IL13
What disease are TH1 and TH2 invovled in?
TH1 --> management of infection
Th2 --> management of allergic disease
Can genetic influences alone cause hypersensitivity?
NOT sufficient for disease
ONLY susceptibility, environment required
Can you have a hypersensitized reaction on your first time encountering the antigen?
No because you can only have a hypersensitive reaction on re-exposure to an allergen to which you have previously been exposed ie. sensitised
What are allergens?
Allergens are Antigens that initiate an IgE mediated response
What is the action of the different TH cells?
TH1 --> fight infection
Th2 --> allergy response
Th17 --> fights infection
Treg --> calm down the pathway and block the others
What cytokine does TH2 produce to get B cells to produe IgE?
What does production of IL-4 by TH2 do?
It signalls to B cells to produce IgE
What is the process of type 1 allergic response?
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 Fab portion of mast cell bound IgE
5) Cross linking causes release of mediators from mast cells and basophils leading to symptoms
What 6 organs are affected in type 1 allergic response?
sensory nerve endings
What is the Immunopathogenesis of IgE mediated allergic response?
IgE Ab mediated mast cell and basophil degranulation- release of preformed and de novo synthesized inflammatory mediators
What is the clinical features of IgE mediated allergic response?
Fast onset (15-30 min)
Wheal and flare
Whats invovled in the late phase response to IgE mediated allergic response?
Central role for Th2 T cell
What is the pathway of the late phase reaction in IgE mediated allergic response?
Arachidonic acid pathway --> produce leukotrienes and/or prostaglandin
What process is invovled in the initial phase reaction of IgE mediated allergic response?
Degranulation --> Granule contents are realeased including histamine
What is the role of Th2 in allergic response?
Multiple cytokine release:
Drive for immunoglobulin
What are the symptoms of RHINITIS?
Blocked nose, runny nose - often with eye symptoms
What can cause rhinitis?
House dust mite, animal danders, pollens
What is the treatment for rhinitis?
Antihistamines ( deal with immediate response) & Nasal steroids ( deal with long term symptoms)
What diseases are in the atopic triad?
Asthma, Rhinitis, Eczema
What type of hypersensitivity is each of the atopic traid diseases?
Asthma - Type 1 hypersensitivity
Rhinitis - Type 1 and 3 hypersensitivity
Eczema - Type 4 hypersensitivity
What is the two types of rhinitis? What is the frequency of rhinitis?
ALLERGIC or NON-ALLERGIC
Can be perennial or seasonal
What is asthma?
Disease of INFLAMMATION & HYPER-REACTIVITY of small airways
In children what triggers asthma?
In childhood - AERO-ALLERGIC stimuli - HOUSE DUST MITE key pathogenic importance
What mediates asthma symptoms?
IMMEDIATE symptoms are IgE-mediated
What process in asthma damages the airways?
DAMAGE TO AIRWAYS due to LATE PHASE RESPONSE
What is the consequence of damaged airways?
DAMAGED AIRWAYS ARE HYPER-REACTIVE to non-allergic stimuli e.g. fumes
What two substances produced by mast cells in late phase response is key in ashtma?
Leukotrienes and Prostaglandins
what are the different types of dermatitis?
1) Atopic - eczema 2) Allergic - type 4 hypersensitivity 3) Non-allergic
How does dermatitis present clinically?
Intense itching, blistering/weeping, cracking of skin
What is thought to be a major cause of atopic dermatitis?
HOUSE DUST MITE
What is treatment for atopic dermatitis?
Topical Steroids & Moisturisers
What is the process in atopic dermatitis that makes people want to itch?
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 different ways of diagnosing allergy?
Specific IgE (>0.35 KuA/L)
Skin prick test (>3mm wheal)
Oral challenge test – Gold standard
Basophil activation test
Component resolved diagnostics
What is 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 advantage and disadvantage of doing specific IgE test?
Dis--> False negatives
What is the advantage and disadvantage of doing skin prick test?
Dis--> False negatives, alse positives, Antihistamines, Slight risk
What are the symptomatic treatment for allergic reaction?
Antihistamines, Steroids, Adrenaline
What is specific treatment for allergic reaction?
Specific – Immunotherapy (Subcutaneous or Sublingual
When is specific immunotherapy used to treat allergic reactions?
Life threatening reactions to Wasp & Bee sting
Severe Hay fever
Animal dander allergy
When is specific immunotherapy not useful in treating allergic reactions?
Allergic rashes – Eczema, Urticaria
What is the general idea of immunotherapy?
Trick the immune system to tolerate the antigen through controlled exposure Switch from Th2 to Th1 response W
What is the 6 most common food allergies?
LEGUMES - PEANUT; SOYBEAN; TREE NUTS
CRUSTACEANS / MOLLUSCS
What is the clinical manifestation of food allergy to the Gastrointestinal,Respiratory , Cutaneous system?
vomiting, diarrhoea, oral symptoms
Respiratory (upper & lower)
role of food in atopic dermatitis unclear