Allergy L14 Flashcards
Define hypersensitivity.
“Excessive immune response that leads to damage”
“Over-reaction of the immune system to harmless agent”
What is hypersensitivity in response to? (4)
Response to pathogen
Response to environmental agents
Response to toxin/pharmacological agent
Response to food
Hypersensitivity Types
Type I - ____1____
Type II - ____2____ mediated
Type III - ____3____ complex mediated
Type IV - ____4____ mediated - “delayed type”
- Immediate
- Antibody
- Immune
- Cell
Type 1- immediate hypersensitivity
- Immediate – occurs within 2 – ___1___ minutes
- Mediated through ___2___ bound to FcεR1 on:
- mast cells, basophils, (eosinophils)
- cells not restricted to a single antigen specificity
- IgE - FcεR1 binding very high affinity
- Local inflammation – atopy (allergy)
- Systemic - ___3___
- 30
- IgE
- Anaphylaxis
The reason people collapse during allergic reactions is the increased ____1____ permeability that causes fluid from the blood to leak into the tissues. This leads to less ____2____ in the blood and therefore less gets to the brain –> collapse (like fainting).
- Vascular
- Oxygen
Read
Early Phase
- wheal and flare
- smooth muscle contraction
- increased vascular permeability
- mucus secretion
Late Phase
- post exposure production of inflammatory mediators
- influx of eosinophils
- recruit Th2 T-cells
- Produce IL4 - stimulates B cells to produce more IgE which leads to – chronic/persistent type I response
A reason why Type 1 often leads to Type 2 is the increased vascular permeability caused by Type 1 allows the movement of many ________ cells to enter the affected tissues. This congregating of ________ cells can lead to Type 2 and more.
Immune
- IgE is secreted by ___1___-cells.
- IgE binds to basophils, readying them for the binding of ___2___.
- ___1___-cells are CD40 positive cells (have CD40 proteins on their surface).
- Basophils have CD40 ligands on their surface.
- When activated by a cross-linking antigen basophils CD40L binds a ___1___-cell CD40 causing the stimulation of IgE production.
- The more IgE production, the more readying of basophils, the more ___1___-cell stimulation and so the more IgE = ___3___ feedback loop.
- B
- Antigens
- Positive
Read
Diagnosis & Treatment: type 1 hypersensitivity
Diagnosis
- challenge with antigen - “skin prick test”
- lab test for IgE
Treatment
- avoidance – desert vacations and sea cruises
- anti-histamines (hives/bee stings)
- beta adrenergic agonists (asthma -salbutamol)
- topical corticosteroids
- carry epinephrine (adrenaline) syringe - anaphylaxis
Desensitisation (can induce anaphylaxis)
Read
Type II - antibody mediated hypersensitivity
- Occurs in 5 – 6 hours
- Consequent upon action of IgG & IgM (cytotoxic)
- Autoimmune disease - Graves’ disease (α-TSHR)
- Hyper-acute allograft rejection (α-donor HLA)
- Haemolytic anaemias:
- haemolytic disease of new-born (α-Rh+)
- incompatible blood transfusion (ABO)
- autoimmune haemolytic anaemias
- response to penicillin
Read
Type III – (immune complex mediated)
- Occurs within 2 – 8 hours
-
Soluble protein plus high affinity IgG
- Pathogen - chronic viral infection (HCV)
- Environmental/therapeutic agent - penicillin
- Subcutaneous inoculum - Arthus reaction
- Auto-antigen – DNA - SLE
- Localised (Farmer’s Lung) – inhaled Ag - IgG not E
- Systemic (serum sickness, HCV, SLE) – lots of Ag
Features of type III hypersensitivity
- Caused by ____1____ complexes – deposited in blood vessels – fix complement and interact with FCR
- Complement activation:
- ___2___ activates mast cells - degranulate - urticaria
- ___3___ recruits inflammatory cells – neutrophils
- Induration - swelling and hardening of tissue
- Platelet accumulation – clots – burst vessels - erythema
- Immune
- C3a
- C5a
