Case 7- Allergies Flashcards
How is histamine produced?
When the antigen binds to the mast cell there is degranulation, one of the main mediators released is Histamine. Histamine then causes allergy symptoms
Effect of histamine release- general
1) Itchiness (Pruritus)
2) Increased smooth muscle contraction-bronchospasm
3) Increased gastric acid secretion- diarrhoea and vomiting
4) Raised Tryptase
Effect of histamine release- blood vessels
Increased blood flow and permeability in the blood vessels. Fluid shifts into the interstitial space causing pulmonary oedema, swollen eyes and lips
Effect of histamine release- mucus
In the eyes, nasal passages and airways there is decreased diameter and increased mucus secretion. This causes congestion and blockage of airways (wheezing, coughing and phlegm). There is swelling and mucus secretion in nasal passages.
Immune tolerance and allergy
A complex system causing suppresion of cellular or humoral immune responses. Allergy occurs due to a failure of this response.
Allergic reaction
A hypersensitivity reaction initiated by immunological mechanism
Allergen
An antigen that triggers an allergic reaction
Atopy
a tendency to develop an allergic disease
Effects of atopy
Atopy is clinically associated with allergic asthma, eczema and allergic rhinitis. It occurs in 20-30% of the population.
The atopy/allergic march
Shows the natural progression of allergies:
Eczema -> Food allergy -> Rhinitis -> Asthma
Type 1 allergic reaction- IgE mediated hypersensitivity
It’s split into sensitation stage and the Re-exposure stage
• On exposure to the allergen, the APC processes the antigen and presents it to the TH2 cell and bind together. (sensitisation).
• When it binds together the TH2 cell release IL-4 and IL-12, these mediators activate the B cell. (sensitisation).
• The B cell proliferates and differentiates into plasma cells that synthesize and secrete IgE antibodies (sensitisation).
• The IgE binds to the mast cells by the Fc region, sensitizing the mast cells. (sensitisation).
• Upon subsequent exposure to the allergen, mast cells with IgE bind to the antigen undergo degranulation releasing inflammatory molecules resulting in allergy symptoms. (Re-exposure)
Examples of type 1 hypersensitivity reactions
Hay fever, Asthma, Hives and Angiodema (swollen lips and eyes) these are localised reactions. Systemic reactions would be anaphylaxis.
Urticaria (hives)
You get it with nettle stings and allergic rashes. It is circumscribed, raised erythematous plaques often with central pallor. It is very itchy. Not all urticaria is caused by allergy for example, stress and viral infection. Can be caused by type 1 hypersensitivity reactions
Angioedema
Usually associated with urticaria, its swollen lips and eyes. There is the involvement of the deeper dermis and subcutaneous tissue. Not all angioedema is allergy.
Anaphylaxis
A severe life threatening, generalised or systemic hypersensitivity reaction. It is characterised by rapidly developing, life threatening air way, breathing and circulatory changes or gastrointestinal changes usually associated with skin and mucosal changes. The trigger may not always be identified.
Type 2 Hypersensitivity: Cytotoxic, antibody mediated
Involves antibody (IgG or IgM) mediated destruction of self cells. • IgG or IgM (antibodies) bind to either an intrinsic or extrinsic tissue. In the intrinsic tissue they will detect the self antigen as a foreign antigen, there will be a failure in immune tolerance. In the extrinsic tissue the foreign antigen will resemble the host cell, it will get absorbed onto cells as part of the infection of a pathogen. • The antibodies bind to the antigens, forming Ag-Ab complexes promoting the classical pathway of complement activation. This will eliminate cells presenting foreign antigens. • Mediators of acute inflammation are generated causing cell lysis and death.
Examples of a type 2 allergic reaction- transfusion reactions
Transfusion reaction produced by mismatched blood. It will destroy foreign RBC by complement-mediated lysis triggered by IgG. This produces fever and intravascular clots. The free Hgb produced will either pass in the urine- haemoglobinuria or breaks down into bilirubin which can be toxic
How long is a type 2 allergic reaction
Hours or days
Examples of type 2 allergic reactions- drugs
• Drug induced Thrombocytopenis- drugs (antibiotics) bind to the surface of platelets the IgG binds to the drug and mediates destruction of platelets by phagocytes through binding of Fc receptors on the cell surface