Hypersensitivity Reaction (Type I) Flashcards
Type I hypersensitivity reactions occur due to the action of what antibody?
IgE
Give an overview of the pathophysiology of type I hypersensitivity reactions
IgE is formed as a result of prior sensitisation (previous contact with antigen) and coats mast cells and basophils.
Subsequent encounter with the antigen results in an IgE mediated reaction with the preformed IgE antibodies.
The free antigen binds to two adjacent IgE antibodies (crosslinking), which causes the cell to degranulate
Is type I hypersensitivity immediate or delayed?
Immediate - within minutes
When mast cell degranularion occurs, what pro inflammatory mediators are released?
Histamine Prostaglandins Heparin Leukotrienes Tryptase and chymase Lysosomal enzymes
How does histamine affect lung bronchi?
Via H1 receptors it causes smooth muscle contraction - narrower airways and difficulty breathing
How does histamine affect blood vessels?
Dilation and increased permeability of vessel walls
- blood flow to affected area increases
- more inflammatory cells and chemicals to site
- fluid leaks into interstitium causing oedema, erythema, warmth
What example allergens are there in type I hypersensitivity reactions?
Seasonal exposure:
Tree and grass pollen
Perennial exposure:
House dust mite
Animal dander
Fungal spores
Accidental exposure: Insect venom - wasp and bee sting Drugs - penicillin, muscle relaxants Food - nuts, shellfish, eggs, wheat, soy, milk Chemicals - latex
What examples of type I hypersensitivity reactions are there?
Asthma
Allergic rhinitis
Anaphylaxis
Describe what happens in phase 1 (sensitisation)
Allergen picked up by antigen presenting cells
APCs carry allergen to lymph nodes and present it to the naive T helper cells there
The T helper becomes a type 2 helper T cell (TH2)
TH2 release IL4 causing B cells to undergo antibody class switching- from IgM to IgE
The IgE produced is specific to the allergen
TH2 also release IL5, which stimulates production and activation of eosinophils
What are antigen presenting cells?
Dendritic cells
Macrophages / monocytes
B cells
Which is the most important interleukin in the sensitisation phase?
IL-4 - it is released from TH2 cells to cause B cells to switch and only produce IgE
What receptor do mast cells and basophils have on their surface that IgE attaches to?
The FCER1 receptor (the FC epsilonR1)
Do the FCER1 receptors on macrophages and basophils have a high or low affinity for the FC portion of antibodies?
High affinity
When does phase 2 occur (the reaction phase)?
When the same allergen enters the body again
The pro inflammatory mediators cause what symptoms?
Itching Hypotension Bronchospasm Shock Abdominal cramping
The reaction phase is subdivided into what 2 phases?
Immediate reaction
Late reaction phase
What is the main difference between the immediate reaction phase and late reaction?
Immediate: chemicals that are already formed and stored are released
Late: new chemicals synthesised, which maintain the reaction for hours
What does histamine do to nerve endings?
Depolarises them - itching and pain
In phase 2, what role does phospholipase have?
It converts phospholipids in the membrane of mast cells into arachidonic acid - the compound from which numerous leukotrienes and prostaglandins are synthesised
What do the newly synthesised chemicals (part of phase 2) cause?
Infiltration of more inflammatory cells at site of allergy
Tissue damage
Smooth muscle spasm
Oedema that can last for days
What is the most potent activator of eosinophils?
IL 5
The late phase reaction is the major cause of symptoms in conditions like…
Asthma
Is it the immune response or the antigen that is harmful?
The immune response - it is inappropriate
Is there a genetic component to allergic reactions?
Yes genes can cause helper T cells to be more hypersensitive to certain antigens.
