Anaphylaxis

What is Anaphylaxis

Anaphylaxis is the medical term for a severe and possibly life threatening allergic reaction. It is most often triggered by the ingestion of a specific food. It occurs after an individual develops initial sensitisation to a food when their immune system mistakenly labels the food as a threat. This causes the immune system to overreact to subsequent exposures releasing inflammatory chemicals such as histamine with potentially life threatening results. The symptoms occur within seconds to minutes of exposure and worsen rapidly. 

Symptoms of Anaphylaxis

Anaphylaxis is likely when the 3 following criteria occur:

  1. Sudden onset of symptoms with rapid progression
  2. Rash, hives or swellings
  3. Life threatening Airway, Breathing or Circulation problems

The symptoms may include:

  • Rash, hives or swellings

  • Difficulty breathing

  • Light headedness, faintness or confusion

  • Nausea, vomiting or abdominal pain

  • Collapse

Common Triggers of Anaphylaxis

  • Foods: Nuts, fish, shellfish, eggs, milk
  • Medication: Antibiotics, Anti-inflammatories, General anaesthetic etc
  • Insect Stings: Wasp and bee stings etc
  • Latex
  • Idiopathic: sometimes there is no obvious trigger

Treatment of Anaphylaxis

  1. Immediate intramuscular injection with an adrenaline pen
  2. Urgently call for an ambulance
  3. Remove any obvious trigger (e.g. peanut present on the lips)
  4. Place the patient sitting or lying down with legs raised
  5. If no improvement then repeat adrenaline injection after 5 minutes

Further information for health professionals

The Immunology of Anaphylaxis

Peanut as a major trigger of food anaphylaxis and will be used the purposes of this piece to demonstrate the immunological basis of the development of either allergic sensitisation or immunological tolerance. Peanut induced anaphylaxis is an immediate Type 1 hypersensitivity reaction which is immunoglobulin E (IgE) mediated and can precipitate a severe and life threatening multisystem response.

Allergic response

There are two phases which are paramount to the development of an allergic response.

Phase one occurs when an atopic individual is first exposed to the allergen peanut. Peanut allergen is taken up by Antigen presenting cells (APC), particularly immature Dendritic cells (DC), via antigen recognition receptors and processed into peptide fragments. The Dendritic cell will move through the lymphatics towards the lymph node inducing DC maturation and resultant upregulation of the APC functional ability. Once in the lymph node, the APC will present this peptide fragment to a naive T cell (Th0) via its surface MHC Class II receptor. Adhesion molecules bind the T cell receptor and the MHC Class II receptor forming and stabilising an immunological synapse. This ensures specificity.

In addition, co-stimulation will activate the T cell via molecules CD80/CD86 on the Dendritic cell binding to CD28 on the T cell. In turn, the T cell will activate the Dendritic cell via CD40L binding to CD40 on the DC upregulating its production. Furthermore, the Th0 cell becomes activated to express cytokines particularly IL-4 which drives the differentiation of these cells to Th2 helper cells, thus triggering clonal T cell expansion with further cytokine production. This creates an environment rich in IL-4 and IL-13 responsible for inducing IgE production from B cells and IL-5 responsible for eosinophil recruitment and activation. The cytokine profile is vital as it will determine the immune response which is a Th2 immune response in this case.

In the meantime, T cell dependent activation of B cells occur with resultant IgM production. The B cell processes the allergen and presents it to clonal Th2 cells’. Activation of the B cells stimulates further cytokine production particularly IL-4 and promotes irreversible Immunoglobulin class switching to peanut specific IgE antibodies. Somatic hypermutation occurs in the Germinal Centre and ensures high affinity for peanut. Peanut specific IgE will attach to mast cells and basophils. This is referred to as sensitisation. Memory B cells are generated and a small number of memory T cells remain.

Phase two occurs on subsequent exposure to peanut. Peanut binds to the sensitised mast cells causing a conformational change and crosslinking of the receptor in turn triggering degranulation of the mast cell releasing pre-stored and newly synthesised inflammatory mediators. This is how anaphylaxis occurs.

Tolerant response

If the immune system can distinguish peanut from being a harmful allergen it will establish tolerance. The balance of peanut tolerance and allergy can be influenced at multiple levels. The principal mediator of tolerance is the dendritic cell. In addition to antigen presentation an activated Dendritic cell will increase costimulatory molecules, augment cytokine production and upregulate MHC class II receptors to allow further antigen presentation. It will ensure that T cells become activated.

There are three main chemicals that will induce activation of a Dendritic cell and these include pro-inflammatory cytokines for example TNF alpha and IL-1 beta, Pathogen associated molecular patterns (PAMPs) and Damage associated molecular patterns (DAMPs). These are also referred to as ‘danger signals’ and play a central role in initiating an immune response.

Where an allergic response occurs there are background danger signals present for example as a result of eczema or an illness. However, in a situation where there are a low level of danger signals, the dendritic cell will migrate to the lymph node as before but it will present antigen in a semi-mature state. This results in reduced production of MHC class II receptors and costimulatory molecules but a substantial increase in production of suppressive cytokines such as IL-10 and TGF-beta. Consequently, the Th0 will differentiate into T regulatory cells (Tregs) rather than T2 helper cell pathway with IgE production. This is a tolerogenic response and will inhibit the development of allergen specific IgE mediated allergic response. Instead Tregs promote the expression and production of Immunoglobulin G4 (IgG4) which will bind to the peanut allergen and thus block the generation of sensitization.