Hypersensitivity Flashcards
What are the mediators for the different hypersensitivity reactions
Type I-III are all antibody mediated
Type IV are T cell mediated
what are the three different types of antigen that can cause a hypersensitivity reaction
self-antigen
environmental substance
infection
what classes of hypersensitivity reactions can be an autoimmune reaction
II, III, IV
what antibody class is implicated in type I, II and III hypersensitivity reactions
I - IgE
II and III = IgG
what is a type I hypersensitivity reaction
Type I hypersensitivity (allergy) reactions are those in which antigen interacts with IgE bound to tissue mast cells or eosinophils resulting in their degranulation. This type of hypersensitivity is some¬ times referred to as immediate hypersensitivity
describe what happens on first and second exposure to the allergen in type I hypersensitivity reaction
Upon first exposure to the allergen this stimulatesIgE production by B cells (result of TH2 cells releasing IL-4). These IgE antibodies then become embedded in the membranes of mast cells, through interactions with the Fc receptors on the surface of the mast cell, exposing the antigen binding sites of the IgE molecules to the microenvironment of the cell. Re-exposure to the antigen causes a bridging effect between adjacent IgE molecules triggering the mast cell to release its mediators. There are two groups of mediators: those that are pre-formed and those that are newly synthesised, which results in an immediate and late response being observed in allergy.
what is the immediate and late phase reaction of a type I hypersensitivity reaction
Because the preformed mast cell mediators, such as histamine and heparin, are pre-synthesised, their release produces effects within 5 to 10 minutes and peak around 30 minutes. The immediate effects causes by these mediators include vasodilation, oedema and vascular congestion.
The newly synthesised mast cell mediators (cytokines) have to be transcribed and translated before being released, which takes a significant amount of time, meaning their affect is usually seen 2 to 24 hours after exposure. The release of the cytokines results in inflammatory infiltrate rich in eosinophils, neutrophils and Th2 cells.
define the allergic march and atopy
Individual that develop an allergy at a young age have an increased risk of developing other allergies throughout their life. While many of their allergies improve over time others appear – known as the allergic march. Such patients are frequently atopic: atopy defines an inherited tendency for overproduction of IgE antibodies to common environmental antigens resulting in an immediate hypersensitivity reaction.
polymorphisms in what protein has been implicated in eczema?
Polymorphisms in the gene for filaggrin are a well-established cause of allergy and has been implicated in 50% of eczema cases. Filaggrin is a protein expressed in the keratinocytes of the skin. It has a role in maintaining epithelial barriers and moisturising surfaces and controlling pH. Thus polymorphisms in this gene means the individual is less effective at maintaining the epithelial barrier or moisturizing the skin.
what are common precipitants for anaphylaxis
food: fish, shellfish, eggs, milk, wheat, nuts
Insect venoms - bee, wasp
Drugs: antibiotics, anaesthetic agents, antisera
how would you investigate someone with a possible allergy
Skin-prick testing is the preferred method for allergy testing. When the antigen introduced by pricking cross-links immunoglobulin E (IgE) on mast cell FcεRI, the rapid release of histamine causes a local flare and a wheal reaction. Skin-prick tests give immediate results, which the patient can see, and they are cheaper and more sensitive than specific IgE testing on blood samples. Skin-prick testing is not possible when patients have taken antihistamines; in these circumstances, measuring levels of specific IgE is most useful.
Alternative is IgE levels (RAST test)
what would be the outcome for someone with a Ara h2 peanut allergy exposed peanuts compared to someone with an Arah8 allergy
- Many people with peanut allergy are allergic to the peanut protein Ara h2. This protein is very stable and is not destroyed by cooking or by gastric acid. In people who are allergic to Ara h2, minute quantities of peanut in food can cause severe systemic reactions even in cooked foods.
- Ara h8, which is an unstable protein that is destroyed by heating and by gastric acid. This means that cooked foods containing peanut are somewhat less risky for people with allergy to Ara h8. Additionally, because the Ara h8 protein is destroyed by gastric acid, it does not have systemic effects and tends to cause symptoms mainly in the mouth and lips.
what are the treatment options for those with allergy
- patient education
- allergen avoidance
- antihistamines - local/systemic
- Steroid - local/systemic
- Leukotrine antagonists
- Densitisation immunotherapy
- Specific treatments
- asthma
- β2-adrenergic agonists, such as salbutamol, mimic the effects of the sympathetic nervous system and work mainly by preventing smooth bronchial muscle contraction in asthma.
- anaphylaxis:
- Epinephrine (adrenaline) is an important drug and can be lifesaving in anaphylaxis where the blood pressure falls dramatically. Epinephrine stimulates both α- and β-adrenergic receptors, decreases vascular permeability, increases blood pressure, and reverses airway obstruction.
- asthma
define a type II hypersensitivity reaction
Type II hypersensitivity reactions are triggered by antibodies (IgG or IgM) reacting with antigens found on the surface of cells or fixed within certain tissues. Once the antibody has bound to the relevant antigen damage arises by:
- stimulating opsonisation and phagocytosis
- inflammation
- abnormal cellular function
Discuss how a type II hypersensitivity reaction can cause opsonisation/phagocytosis
Antibodies that bind to cell surface antigens may directly opsonise cells, or they may activate the complement system, resulting in the production of complement proteins that opsonise cells.
These opsonised cells are phagocytosed and destroyed by phagocytes that express receptors for the Fc portions of the IgG antibodies and receptors for complement proteins.
