Allergic Disease and Immunology Flashcards
Define hypersensitivity reaction.
A reaction of the immune system that is detrimental to the host, which is either:
- A normal immune response triggered and persistent in the absence of a true pathogen.
- An inappropriately exaggerated immune response.
Describe the 4 types of hypersensitivity reactions.
Type 1 - Type I IgE mediated mast cell degranulation and activated eosinophils and basophils.
Type 2 - Self IgG antibodies bind antigens on the patient’s own cell surfaces and cause damage directly.
Type 3 - Immune complexes formed of circulating antigen and IgG.
Type 4 - Cellular immune responses mediated by T cells.
Which of the 4 types of hypersensitivity reactions is known as allergy?
Type I.
List 6 examples of type 1 hypersensitivity reactions (allergies) in order of severity.
1 - Hay fever.
2 - Allergic asthma.
3 - Atopic dermatitis.
4 - Food allergy.
5 - Drug allergy.
6 - Latex allergy.
Give an example of a type II hypersensitivity reaction.
Autoimmune haemolytic anaemia.
List 2 examples of type III hypersensitivity reactions.
1 - Arthus reactions.
2 - Immune complex disease.
List 2 complications of type III hypersensitivity reactions.
1 - Glomerulonephritis.
2 - Vasculitis.
What are type IV hypersensitivity reactions otherwise known as?
Delayed hypersensitivity reactions.
List 2 examples of type IV hypersensitivity reactions.
1 - Contact dermatitis.
2 - Mantoux test (tuberculin reaction).
Which 2 types of hypersensitivity reaction are most common clinically?
Type 1 and 4.
How do type 1 and type 4 hypersensitivity reactions differ in time between exposure and onset?
- Type 1 hypersensitivity reactions occur immediately after exposure.
- Type 4 hypersensitivity reactions occur >4 hours after exposure.
How do type 1 and type 4 hypersensitivity reactions differ with regards to severity?
- Type 1 hypersensitivity reactions are often life threatening.
- Type 4 hypersensitivity reactions are often severe but not life threatening.
How do type 1 and type 4 hypersensitivity reactions differ with regards to the allergen that causes them?
The allergen is usually more difficult to identify with type 4 hypersensitivity reactions.
What is patch testing?
When is it used?
- A method used to determine whether a substance causes allergic inflammation of a patient’s skin.
- Used in the diagnosis of contact dermatitis.
Define sensitisation.
A phenomenon where the immune system recognises an allergen but doesn’t necessarily induce systemic symptoms.
Define atopy.
Predisposition to allergic disease.
Define anaphylaxis.
A severe, life threatening IgE mediated type 1 hypersensitivity (allergic) systemic or generalised reaction characterised by a dramatic fall in blood pressure and severe airway constriction.
Define anaphylactoid.
A severe, life threatening non-IgE mediated systemic reaction that mirrors anaphylaxis in clinical presentation.
List the steps involved in type 1 hypersensitivity reactions.
1 - Allergen exposure.
2 - Sensitisation.
3 - Specific IgE production.
4 - Re-exposure to allergen and allergic response.
What is the relative (qualitative) concentration of IgE in the blood compared with other immunoglobulin classes?
Very low.
List 2 reasons for why IgE concentration might increase during type I hypersensitivity reactions.
1 - Increased production.
2 - Increased class switching to IgE.
List 2 cytokines required for IgE class switching.
1 - IL-4.
and / or
2 - IL-13.
Via which receptors does the IgE constant region bind to allergy effector cells?
FceR1.
List the allergy effector cells.
1 - Mast cells.
2 - Basophils.
Give an example of an enzyme that is used to diagnose anaphylaxis.
Why is it useful in diagnosing anaphylaxis?
What is the function of this enzyme?
- Tryptase.
- Because it is long-lasting (about 8 hours after the onset of anaphylaxis).
- Tryptase is a mast cell mediator that is released by activated mast cells which has a role in inflammation.
List 4 early phase mast cell mediators.
1 - Histamine.
2 - Kallikrein.
3 - Serotonin.
4 - Proteases.
List 4 late phase mast cell mediators.
1 - Tryptase.
2 - Leukotrienes.
3 - Prostaglandins.
4 - Cytokines.
What is the function of kallikrein?
Kallikrein activates bradykinin which causes increased vascular permeability.
What is the general function of late phase mast cell mediators?
To promote cellular upregulation and secretion.
List 7 effects of mast cell mediators.
1 - Vasodilation.
2 - Bronchoconstriction.
3 - Increase heart rate.
4 - Increase heart contractility.
5 - Increase glandular secretion.
6 - Increase vascular permeability.
7 - Irritation of nerve endings.
List 3 treatments of anaphylaxis.
1 - Intramuscular adrenaline.
2 - Steroids.
3 - Antihistamines.
Give an example of a visual feature of allergy effector cells.
They are highly granular.
List 3 secretions of mast cells and basophils.
1 - Histamine.
2 - IL-4.
3 - IL-13.
Where are mast cells, basophils and eosinophils located?
- Mast cells are concentrated in tissues.
- Basophils circulate in the blood and migrate to lymph nodes and prime for allergic responses (by undergoing IgE class switching)
- Eosinophils circulate in the blood and migrate to tissues.
Which molecule promotes haematopoiesis in the bone marrow to produce eosinophils?
Which cells release this molecule?
- IL-5.
- CD4+ Th2 cells.
Which molecules promote chemotaxis of eosinophils?
Eotaxins.
List 2 roles of eosinophils.
1 - Control of anti-helminth immunity.
2 - Control of allergic disease.
List 4 type 1 hypersensitivity reactions (allergies) in order of age of onset.
1 - Allergic dermatitis.
2 - Food allergies.
3 - Asthma.
4 - Rhinitis.
List 3 genetic and 3 environmental causes of allergic disease.
Genetic:
Epistasis between genes such as:
1 - IL4R gene.
2 - FceR1 gene.
3 - Filaggrin gene.
Environmental:
1 - Early life exposure.
2 - Infections.
3 - Hygiene.
What is the hygiene hypothesis of allergic disease?
- The lack of exposure to germs in early life skew the immune system away from a Th1 phenotype to a Th2 phenotype.
- Th2 cells release interleukins 3, 4, 5, 9 and 13, which cause:
1 - Mast cell activation.
2 - IgE class switching.
3 - Eosinophil activation and recruitment.
What is the primary purpose of IgE-mediated immune responses?
To promote killing of parasites:
- Helminths are recognised by mast cells as the first line of defence.
- This occurs near body surfaces, where mast cells are abundant.
- The response increases lymph and blood flow, causing angioedema.
- The response involves mast cells recruiting other effectors.
Describe the process of parasite killing.
1 - IgE binds to the parasite.
2 - Eosinophils bind to IgE via the FceR1 receptor.
3 - Eosinophils release toxic lysosomal granules containing major basic protein, ribonucleases, peroxidases, ROS and nitrogen radicals.
Describe the process of parasite eradication.
Il-13 released from effector cells causes:
1 - Goblet cell hyperplasia.
2 - Increased mucus production.
3 - Increased smooth muscle contraction in the GIT.