Allergy and Hypersensitivity Flashcards
What is hypersensitivity?
This is an excessive or unnecessary immune response in which host tissue is damaged in some way
What is Allergy?
This is a hyper immune response to an allergen which may be local or dispersed
What are the 4 types of hypersensitivity under the Gell and Coombs classification?
Type 1 which is IgE mediated
Type 2: Which is IgG antibodies reacting to surface antigens
Type 3: Which is immune complexes mediated by soluble antigen mediated
Type 4 whch is cell mediated and sometimes known as delayed type hypersensitivity
What is the Th1 vs Th2 paradigm?
Th1 cells result in a strong T cell mediated response which is provoked mainly by intracellular pathogens while Th2 causes a strong B cell mediated response which is provoked mainly by extracellular pathogens
What is the relationship between people who have allergy and IgE serum levels?
The vast majority of people who have allergies have higher levels of IgE in their serum
Why do we have IgE responses?
These provide a defence against large helminths and other large parasites
Normal IgG/FcR-mediated activity is typically ineffective at dealing with these pathogens so a larger range of effector responses are required these must be rapid and extensive to deal with complex organisms such as parasites
What is a multivalent allergen?
This is one that crosslinks IgE molcules that are previously passively bound to high affinity FcepsilonR1 on mast cells
What does allergy require?
Preformed IgE so the patient must have been previously exposed to the allergen
What type of exposure favours an IgE response?
A low dose of a complex antigen via the mucosal route
An example of this is allergic rhinitis caused by pollen
What are Mast cells designed to do?
They are designed to dump toxic mediators which can kill complex organisms like parasites as well as releasing pro-inflammatory mediators
What are the early stage or preformed mediators released by Mast cells?
Histamine, herapin
Enzumes such as tryptase, beta-glucosmainidase
Chemotactic and activating factors including eosinophil chemotactic factor, Neutrophil chemotactic factor and platelet activating factor
What are the late stage mediators that are synthesized after activation released by mast cells?
Lipoxygenase pathway products such as SRS and other leukotrienes
Cyclo-oxygenase products like prostaglandins and thromboxanes
Anaphylotoxins
Cytokines which drive Th2 responses
Bradykinin
What is the typical result of local inflammation?
Vasodilation Vascualr leakage Oedema Smooth muscle contraction Mucus secretion Pruritis
What are the common causes of Rhinitis?
House dust mite
Pollens
Animal dander
What are small molecules that commonly allergens?
Penicillin
Codeine and morphine
Synthetic ACTH
What are the common food allergies?
Wheat protein
Milk proteins
Peanuts
Strawberries
What occurs with anaphylaxis in the eyes?
Allergic conjunctivitis
What occurs with anaphylaxis in the respiratory tract?
Allergic rhinitis (hay fever, perennial rhinitis) Sinusitis (Sinuses lined by respiratory epithelia) Asthma (allergic component in 80% of all cases)
What occurs with anaphylaxis in the skin?
Eczema (atopic dermatitis)
Urticara (wheals)
Angioedema (deeper skin involvement-swelling)
What occurs with anaphylaxis in the gut?
Food allergy (diarrhoea, abdominal cramps and vomiting)
What occurs with multiple organ anaphylaxis?
Generalized anaphylaxis or shock
What is anaphylactic shock?
This is a generalized anaphylatic reaction with widespread vasodilation and capillary leakage which causes very low blood pressure and can be fatal
What are monovalent allergens?
These are typically small antigens like penicillin and they are insufficient in themselves to crosslink IgE FcR but instead work through the covalent attachment to proteins
What role might genetic control of IgE play in allergy?
IL-4 and IL-13 are both Th2 cytokines which favour class switching to IgE production the genes for cytokines of the IL-4 cluster like close together on chromosome 5 Antoher gene ofr atopy may be a variant of the IgE Fc receptor gene
What is the hygiene hypothesis?
This suggests that there is less childhood exposure to old infection which would otherwise bias the respiratory lymphoid tissue towards Th1 with the theory being that we are too clean and our lung immune response is predominately towards the default Th2
How can allergy be treated?
Allergen avoidance
Antihistmaines
Corticosteroids
Cromoglycate
Sympathomimeitcs
Desensitization immunotherapy where low doses of allergen are injected to generate competing high affinity IgG or IgA
Rapid desensitization through IgE depletion
What is type 2 hypersensitivity?
This is antibody/surface mediated and involves complement fixation with targeting for phagocytosis
It can be a result of incompatible blood transfusion
Also includes reactions like haemolytic disease fo the newborn and autoimmune haemolytic anaemia
What is type 3 hypersensitivity?
This is immune complex mediated where there is binding of Ig and a complementary antigen which can then promote complement activation
The immune complex will stay in the tissue or circulation instead of being cleared, this is dependent on the size and solubility of the complex
The direct actions of the complement cascade products result in the recruitment of inflammatory cells and activation of platelets
What is the classical example of type 3 hypersensitivity?
Serum sickness which is caused by injection of a foreign protein, passive immunity with immunoglobulin from another species can often result in this where the patient will develop a high concentration of immune complexes containing antigen this is one of the reasons therapeutic mabs need to be fully humanized
What are the common regions damaged in type 3 hypersensitivity?
The complexes often deposit in the skin to cause rashes, joints to cause arthritis and the kidney to cause nephritis they may also induce vasculitis with formation of a microthrombus
How is there overlap between type 2 and 3 hypersensitivity?
Many antigens that are in the soluble phase attach to surfaces and then the antibody binds them
This is the postulated mechanism for vasculitis and glomerulonephritis
What are localized immune complex diseases caused by type 3 hypersensitivity?
Farmers lung where there is lung inflammation caused by inhaling actinomycetes in the hay
IgG antibodies from the blood meet the fungal spore antigens in the lungs leading to complement activation
What is type 4 hypersensitivity?
This is a slow form of hypersensitivity which is affected by memory
Antigen enters tissue where it is processed by APCs, a Th1 effector recognizes the antigen and releases cytokines which act on vascular endothelium
There is recruitment of T cells, phagocytes and plasma to the site of antigen injection causing a viable lesion
What is the classical example of type 4 hypersensitivity?
The mantoux test which is used to test for Tuberculosis exposure
This is when there is an intradermal injection of a purified protein derivative of tuberculin followed by slow development of a raised lump from 48-72 hours later whit the surrounding redness not measured
What is contact sensitivity?
This is a result of type 4 hypersensitivity where things such as metals on jewellery attach onto host proteins and form neo-epitopes which nickel appearing to be the main culprit
This is a possible major mechanism in several disease of an autoimmune nature
