How it works?

Anaphylaxis occurs when a person is reexposed to a specific antigen that cross-links antigen- specific IgE molecules, which are bound to mast cells and basophils.
This leads to activation and degranulation of mast cells and basophils. Preformed mediators, such as histamine and tryptase, within the mast cell and basophil are released in degranulation. The metabolism of arachidonic acid in the cell membrane produces other mediators, such as prostaglandins and leukotrienes.
These mediators act on receptors to induce mucus production, pruritus, vascular permeability, smooth-muscle constriction, and other symptoms of anaphylaxis (Rusznak, 2002). Rapid release of large quantities of mediators systemically will cause capillary leakage and mucosal edema, resulting in shock and asphyxia (Ewan, 1998).


Immunological Mechanism of Anaphylaxis:
(1) Antigen-presenting cell internalizes antigen. (2) The APC processes the internalized antigen. (3) The APC presents the processed peptide to CD4+ T lymphocytes via MHC II. (4) After the peptide is presented, the T cell differentiates into TH2 lymphocytes and produces IL-4, IL-5, IL-9, and IL-13. (5) IL-4 and IL-13 cause B cell immunoglobulin isotype switching to IgE. (6) The circulating IgE binds to the IgE receptors on mast cells. (7) Antigen similar to the original antigen cross-links the mast cell surface-bound IgE, resulting in cellular degranulation. Degranulation releases histamine, tryptase, and other mediators that produce the symptoms of anaphylaxis (Anaesthesia UK, 2005).

Figure 1: Overview of Immunological Mechanism of Anaphylaxis. This figure illustrates each step of the immunological mechanism for anaphylaxis. Figure taken from Anaesthesia UK( 2004), permission pending.

Now as we discuss in the following post, there are 3 different kinds of allergies that causes Anaphylaxis and these includes,




1. Drug Allergy:

Some drugs (polymyxin, morphine, x-ray dye, and others) may cause an anaphylactic-like reaction (anaphylactoid reaction) when people are first exposed to them. This is usually due to a toxic reaction, rather than the immune system response that occurs with "true" anaphylaxis.
The symptoms, risk for complications without treatment, and treatment are the same, however, for both types of reactions. These are the common antibiotics that are associated with anaphylaxis:

Penicillin
Cephalosporins
Tetracycline
Nitrofurantoin
Vancomycin
Chloramphenicol
Bacitracin
Neomycin
Kanamycin
Amphoterin B

The immune system protects the body from potentially harmful substances by recognizing and responding to antigens. Antigens are molecules (usually proteins) on the surface of cells, viruses, fungi, or bacteria. The immune system recognizes and destroys substances that contain these antigens.
Even your own body cells have proteins that are antigens. These include a group of antigens called HLA antigens. Your immune system learns to see these antigens as normal and does not usually react against them.
A histocompatibility antigen blood test looks at proteins called human leukocyte antigens (HLAs), which are found on the surface of nearly every cell in the human body. HLAs are found in large amounts on the surface of white blood cells. They help the immune system tell the difference between body tissue and foreign substances.


2. Food Allergy:

Examples of food allergy:

• milk (caseins and the whey protein b –lactoglobulin)



• eggs (egg white proteins ovomucoid, ovalbumin, and ovotransferrin



• peanuts and tree nuts (proteins used by the seed)



• nuts from trees (including Brazil nuts, hazelnuts, almonds and walnuts)
  
  
• fish (flesh proteins called parvalbumins)



• shellfish eg.including mussels, crab and shrimps (flesh and are part of the muscle protein system, whilst shrimps, allergens have also been found in the shells



• soya ( proteins)



• wheat ( wheat gluten)
  

So what is a Food Allergy?!


Our bodies are protected from infections by our immune system. We produce a type of proteins, called antibodies, which recognise the germs causing an infection. There are a number of different sorts of antibodies, and the one which causes an allergic reaction is called IgE.

Free IgE antibodies (green) cleave to food antigens (red stars) e.g. milk proteins. This cleavage forces the IgE ab to coat the mast cell signalling a danger. The mast cell releases granules of chemical toxins. These granules burst and release these potent chemicals which bring on the allergy attack.

The IgE acts like a tag, sticking to molecules in food or pollen called allergens. When someone who has an allergy eats a problem food the IgE attaches to the allergens, setting off an allergic reaction. One of the common effects that IgE triggers is the release of histamine, which causes the changes we see in our bodies as symptoms, like nettle rash or wheezing.


Allergens are usually proteins, and there are generally several kinds of allergen in each food. It is not fully understood why some foods can cause allergies and others do not, but a theory is that it is probably that some proteins in foods mimic very closely proteins present in viruses and bacteria.


Hence, in some persons, usually this is genetically predisposed, as our immune system is not able to distinguish the food protein from the virus or bacteria one, hence it attacks.



3. Insect Stings:

Examples:

Honeybees
Yellow jackets
Hornets
Wasps
Fire Ants


I will talk about bee stings since this is the most common stings among all.


Bees stings























Do you know that the venom of bees, wasps and fire ants contains phospholipase A2, hyaluronidase, apamin, meliltin, and kinins.




Our body quickly overreacts with histamine production. Histamine is found in higher concentrations in skin, lungs, and stomach mucosa. The release of histamine from the mast cells is usually triggered by skin disruption, i.e. bee sting. Histamine is a potent arterial dilator. Individuals therefore can become hypotensive (lowering of blood pressure) and may pass out.





Histamine can cause inflammation directly as well as indirectly. Upon release of histamine by an antigen activated mast cell, permeability of vessels near the site is increased. Thus, blood fluids (including leukocytes, which participate in immune responses) enter the area causing swelling. This is accomplished due to histamine’s ability to induce phosphorylation of an intercellular adhesion protein (called (VE)-cadherin) found on vascular endothelial cells (Andriopoulou et al 1999). That is why histamine is known as being vasoactive. Gaps between the cells in vascular tissue are created by this phosphorylation, allowing blood fluids to seep out into extracellular space. Indirectly, histamine contributes to inflammation by affecting the functions of other leukocytes in the area. It has been suggested by Marone et al that histamine release triggers the release of cytokines and inflammatory mediator by some neighboring leukocytes (1999). These chemicals in turn increases the inflammatory response.





Interesting Facts about bee stings:
Average adult can withstand approximately 1000 stings
500 stings can kill a child.
Anaphylaxis and death can occur from one sting if the individual is highly allergic.
Therefore do not worry if you get stung by a bee unless you are allergic to it!!!













Common Agents involved in Anaphylaxis and their mechanisms
(n.d.) Anaphylaxis. Retrieved from 6th February 2010.From,
http://www.allergysa.org/anaphyl.htm

Survive Outdoors.(2000). Pathophysiology of Bee Stings. Retrieved from 6th February 2010. From,
http://www.surviveoutdoors.com/reference/beeswasps/index.asp

Medical News Today.(2010).Common Food Allergies. Fetrieved from 6th February,2010. From,
http://www.medicalnewstoday.com/articles/8624.php

Medicine Net.com We bring Doctor’s knowledge to you.(n.d.) Anaphylaxis (cont.). Retrieved from 6th feb 2010.From
http://www.medicinenet.com/anaphylaxis/page5.htm
Food Reactions.(2005) Food Allergy.Retrived from 6th February 2010.From
http://www.foodreactions.org/allergy/

MedlinePlus. (n.d.) Histocompatibility antigen test.Retrieved from 6th feb 2010. from,
http://www.nlm.nih.gov/medlineplus/ency/article/003550.htm


Anaphylaxis, Davidson collage.(2010) Retrived 5th Feb 2010 from: http://www.bio.davidson.edu/courses/immunology/Students/spring2006/Witcher/Anaphylaxis.html