Allergy and Hypersensitivity

Question 1

What is hypersensitivity?

Answer 1

This is an excessive or unnecessary immune response in which host tissue is damaged in some way

Question 2

What is Allergy?

Answer 2

This is a hyper immune response to an allergen which may be local or dispersed

Question 3

What are the 4 types of hypersensitivity under the Gell and Coombs classification?

Answer 3

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

Question 4

What is the Th1 vs Th2 paradigm?

Answer 4

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

Question 5

What is the relationship between people who have allergy and IgE serum levels?

Answer 5

The vast majority of people who have allergies have higher levels of IgE in their serum

Question 6

Why do we have IgE responses?

Answer 6

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

Question 7

What is a multivalent allergen?

Answer 7

This is one that crosslinks IgE molcules that are previously passively bound to high affinity FcepsilonR1 on mast cells

Question 8

What does allergy require?

Answer 8

Preformed IgE so the patient must have been previously exposed to the allergen

Question 9

What type of exposure favours an IgE response?

Answer 9

A low dose of a complex antigen via the mucosal route

An example of this is allergic rhinitis caused by pollen

Question 10

What are Mast cells designed to do?

Answer 10

They are designed to dump toxic mediators which can kill complex organisms like parasites as well as releasing pro-inflammatory mediators

Question 11

What are the early stage or preformed mediators released by Mast cells?

Answer 11

Histamine, herapin
Enzumes such as tryptase, beta-glucosmainidase
Chemotactic and activating factors including eosinophil chemotactic factor, Neutrophil chemotactic factor and platelet activating factor

Question 12

What are the late stage mediators that are synthesized after activation released by mast cells?

Answer 12

Lipoxygenase pathway products such as SRS and other leukotrienes
Cyclo-oxygenase products like prostaglandins and thromboxanes
Anaphylotoxins
Cytokines which drive Th2 responses
Bradykinin

Question 13

What is the typical result of local inflammation?

Answer 13

Vasodilation
Vascualr leakage
Oedema
Smooth muscle contraction
Mucus secretion
Pruritis

Question 14

What are the common causes of Rhinitis?

Answer 14

House dust mite
Pollens
Animal dander

Question 15

What are small molecules that commonly allergens?

Answer 15

Penicillin
Codeine and morphine
Synthetic ACTH

Question 16

What are the common food allergies?

Answer 16

Wheat protein
Milk proteins
Peanuts
Strawberries

Question 17

What occurs with anaphylaxis in the eyes?

Answer 17

Allergic conjunctivitis

Question 18

What occurs with anaphylaxis in the respiratory tract?

Answer 18

Allergic rhinitis (hay fever, perennial rhinitis)
Sinusitis (Sinuses lined by respiratory epithelia)
Asthma (allergic component in 80% of all cases)

Question 19

What occurs with anaphylaxis in the skin?

Answer 19

Eczema (atopic dermatitis)
Urticara (wheals)
Angioedema (deeper skin involvement-swelling)

Question 20

What occurs with anaphylaxis in the gut?

Answer 20

Food allergy (diarrhoea, abdominal cramps and vomiting)

Question 21

What occurs with multiple organ anaphylaxis?

Answer 21

Generalized anaphylaxis or shock

Question 22

What is anaphylactic shock?

Answer 22

This is a generalized anaphylatic reaction with widespread vasodilation and capillary leakage which causes very low blood pressure and can be fatal

Question 23

What are monovalent allergens?

Answer 23

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

Question 24

What role might genetic control of IgE play in allergy?

Answer 24

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

Question 25

What is the hygiene hypothesis?

Answer 25

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

Question 26

How can allergy be treated?

Answer 26

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

Question 27

What is type 2 hypersensitivity?

Answer 27

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

Question 28

What is type 3 hypersensitivity?

Answer 28

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

Question 29

What is the classical example of type 3 hypersensitivity?

Answer 29

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

Question 30

What are the common regions damaged in type 3 hypersensitivity?

Answer 30

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

Question 31

How is there overlap between type 2 and 3 hypersensitivity?

Answer 31

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

Question 32

What are localized immune complex diseases caused by type 3 hypersensitivity?

Answer 32

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

Question 33

What is type 4 hypersensitivity?

Answer 33

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

Question 34

What is the classical example of type 4 hypersensitivity?

Answer 34

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

Question 35

What is contact sensitivity?

Answer 35

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