T3: Hypersensitivity Flashcards
Explain the role of IgE in Type I hypersensitivity.
Type 1 Hypersensitivity
- IgE antibody mediated on the mast cell and basophil degranulation. Released of preformed and de novo synthesized inflammatory mediators
- Fast onset of symptoms (within an hour)
- Eosinophils are seen in the late response and central role of Th2 cell.
The mast cell is in the mucosa and the tissues and so can cause swelling. Binding can cause degranulation through intracellular messaging. Histamine, protease and chemotaxic factors are released. In the late response, there is release of prostaglandins and leukotrienes leading to a by-phasic response.
What is the effect of histamine on different organ systems?
The effect of histamine:
- Blood clots
- Gastric-acid secretion – in anaphylaxis you can vomit
- Blood vessels dilate – leading to a drop in blood pressure which can make you feel dizzy or even collapse
- Bronchoconstriction – can cause wheezing and symptoms of SOB
- Increases the permeability of the capillaries - swelling. This can affect anywhere even the airway. Can be a contributor to the rash seen (urticaria wheels).
- Adrenaline is released – tachycardia
- Swelling and inflammation – urticaria and an itchy red rash
- Frequent heart beat
What is anaphylaxis?
Anaphylaxis is a medical emergency. It is an acute, life-threatening, IgE mediated systemic hypersensitivity reaction.
Severe-moderate reaction (anaphylaxis) shows some of these symptoms:
- Diffuse urticaria and angioedema
- Severe abdominal pain, vomiting diarrhoea
- Hoarseness, cough
- Shortness of breath
- Wheezing and cyanosis
- Respiratory arrest
- Hypotension
- Dizziness, loss of consciousness
Why do we get allergies?
Components of the immune system which would historically be used in parasitic infections are used. The system has developed to produce a rapid tissue-based response to re-infection. The lack of infectious drive is a contributory factor in allergic disease. There is a combination of genetic and environmental factors.
How do we get sensitised?
The allergen is sampled by the dendritic cell – this is a APC which is constantly sampling its environment and presenting them to see if a response needs to be made. It then presents this to a naïve T cell. This recognizes the allergens and differentiates into a type 2 cell. Th2 sends key chemical messages and so there is communication to the naïve B cell (through IL4 and IL13). The Naive B cell switches to produce IgE. The memory B cell then produces IgE antibodies on a low basis.
It has been suggested that early cutaneous exposure to food protein through a disruption skin barrier leads to allergic sensitization and so is why eczema has been seen as a risk factor.
What are the genetic influences on the allergic immune response?
A specific allergy does not necessarily pass down form a parent to a child. An adult allergy is a polygenic disease. Contributories may include the cytokine gene cluster, IL12 and IL4 receptors (differences in responsiveness to cytokines may contribute to susceptibility) and IgE receptor; the presence of TNF-alpha and INF-gamma differences in release etc.
What is the atopic triad?
Atrophic triad – Asthma, rhinitis and Eczema
These diagnoses tend to come together. In terms of rhinitis:
- Can be allergic or non-allergic. Allergic is a perennial (all year round) or seasonal blocked nose, runny nose – often with eye symptoms.
- House dust mites, animal dander and pollen can also have an effect
- Treatment is nasal steroids and
Asthma:
- Disease of inflammation and hyperactivity of the small airways
- In childhood – aeroallergic stimuli tend to worsen asthma, also house dust mites
- Can be damage to the airways due to late phase response
- Allergies can make asthma worse
- Immediate symptoms are IgE mediated
Eczema:
- Atophic eczema includes different types of dermatitis. Some are contact, others non-contact
- Have intense itching, blistering/weeping and cracking of the skin
- Require topical creams and sometimes need steroid.
How do we diagnose of allergies?
Diagnosis
- History
- Specific IgE blood test – there is a threshold cut off. A higher number does not necessarily mean a more severe response.
- Skin prick test – gold standard. A positive test and a control is placed on the skin and the skin is scratched. The patient then is tested to see if a reaction appears. 15 minutes to see a wheel appears. This can be combined with the specific IgE test.
- Oral challenge test Intra-dermal test – for drug testing. The allergen is put into the skin. This is the gold standard. Very rarely do this, avoid to put at risk.
- Component resolved diagnostics – a blood test more specific to the types of allergens within one protein.
Explain the immunopathogeneisis of type II hypersensitivity?
Cytotoxic
The mechanism - IgG/IgM Ab response against combined self/foreign antigen at the cell surface
This triggers complement activation/phagocytosis/antigen dependent cytoxcity
Clinical features
- Onset minutes to hours
- Cell lysis and necrosis
Common antigens include Penicillin.
Use Blood transfusion as an example of Type II hypersensitivity.
In a blood transfusion reaction, the patients antigen presenting cells (dendritic cells to macrophage) detect the foreign antigen. They present it to B cells which make antibodies. This will activate complement and have cytotoxic action. MAC attack complexes are generated as a part of the activation of the classical pathway. This can take hours to a day.
The MAC complex includes C5 to C9 proteins and results in a hole in the membrane and causes leakage of intracellular fluid. C1 bind IgG and IgM and allows the complement pathway to occur.
Explain the immunopathogenesis of type III hypersensitivity.
Mechanism
*IgG/IgM Ab against soluble antigen - immune complex deposition. It is much smaller than the cell in type II.
Clinical features
*Onset 3-8h and it can cause a vasculitis
Give an example of an associated Type III hypersensitivity disease.
SLE
SLE is an example of type III sensitivity. Normally our blood cells are tolerant to DNA and antigens, they do not react to self. If this goes wrong, an antibody can recognize our antigen, in this case DNA. This results in autoimmunity. The DNA most likely leaked from the cell. You then get clonal expansion of the cell producing the anti-DNA antibody. Small immune complexes result. These do not get cleared as easily form the system and stick to the blood vessel wall.
C1 then binds to the antibody and C1-9 follow with increased permeability of the vessels. C3 and 4 used in large amounts – this is used in a blood test.
Describe Type IV hypersensitivity.
*Mechanism - Antigen specific T-cell mediated cytotoxicity. Not mediated by antibodies.
Clinical features
- Delayed onset 48-72h
- Erythema induration – redness of the skin
Common antigens
- Metals- e.g. nickel
- Tuberculin test
- Poison Ivy
Associated diseases include Contact dermatitis
