Systemic Anaphylaxis

Table 1. Key concepts about the roles of mast cells in systemic anaphylaxis in mice and humans... 

Although human anaphylaxis is a systemic reaction, the mouse model of passive cutaneous anaphylaxis (PGA) has been used extensively to enhance our understanding of mechanisms which also may contribute to systemic anaphylaxis. Unlike systemic anaphylaxis in the mouse, PGA appears to be entirely dependent on mast cells [4,6]. While IgE appears to be the primary antibody isotype that mediates PCA reactions in actively immunized mice, activation of FcyRIII by a fraction of IgGl antibodies (called anaphylactic IgGl) can also mediate PCA reactions in mice [4]. 

TsujimuraY, ObataK, Mukai K, Shindou H, Yoshida M, Nishikado H, Kawano Y, Minegishi Y, Shimizu X Karasuyama H Basophils play a pivotal role in SS immunoglobulin-G-mediated but not immuno-globulin-E-mediated systemic anaphylaxis. Immunity 2008 28 581-589. 

Kinet JP, GaUi SJ Systemic anaphylaxis in the mouse can be mediated largely through IgGl and FcyRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active 35 or IgE- or IgGl-dependent passive anaphylaxis. J Clin Invest 1997 99 901-914. 

Few prospective studies of induced anaphylaxis have been performed in human subjects to imderstand the molecular basis of systemic anaphylaxis, because of the potentially rapid, Ufe-threatening outcome. Accordingly, various models of anaphylaxis have been estabUshed in laboratory animals, particularly mice, and extensively studied to clarify the underlying mechanisms. Such studies revealed that the classical pathway utilizing mast cells, IgE and histamine cannot explain all cases of anaphylaxis. 

Fig. 2. IgG-mediated systemic versus local anaphylaxis, a IgG-mediated systemic anaphylaxis. When allergen-IgG immune complexes are formed in the circulation, basophils immediately capture them through IgG receptors on their surface and are activated to release PAF, that in turn act on vascular endothelial cells, leading to increased vascular permeability, b Passive cutaneous anaphylaxis. When allergen-IgG immune complexes are formed in the skin, they stimulate tissue-resident mast cells to release chemical mediators such as histamine, leading to local inflammation. 

Basophils Release Platelet-Activating Factor Instead of Histamine to Induce IgG-Mediated Systemic Anaphylaxis... 

Systemic anaphylaxis is the most dramatic and potentially fatal manifestation of immediate hypersensitivity, accounting for more than 500 deaths annually [ 1 ]. Despite these alarming findings, there is surprisingly limited interest and little information on how the cardiovascular system is involved in fatal and near-fatal allergic diseases. 

Pathological observations indicate that lesions of the cardiovascular system can be a cause of death in patients with anaphylaxis [2], Myocardial lesions might be the anatomical basis for the irreversible cardiac failure occasionally associated with systemic anaphylaxis [3]. There is compelling evidence that the heart is directly and/or indirectly involved in several forms of anaphylaxis in man [1,4,5]. 

Systemic anaphylaxis in man is frequently accompanied by electrocardiographic alterations ischemic ST waves, arrhythmias and atrial fibrillation [6-11]. Anaphylactic reactions after insect stings can lead to coronary spasm or acute myocardial infarction [12, 13]. Myocardial infarction can also occur as a consequence of idiopathic... 

Physical factors, such as heat, mechanical stimulation and exercise, may sometimes lead to mast cell degranulation and whealing in the skin, but rarely provoke systemic anaphylaxis [4, 26]. Patients do report that these and other factors in combination (such as exercise, heat and alcohol) may elicit anaphylaxis in summation. 

Foster B, Schwartz LB, Devouassoux G, Metcalfe DD, Prussin C Characterization of mast-cell try-ptase-expressing peripheral blood cells as basophils. J Allergy Clin Immunol 2002 109 287-293. Schwartz LB, Bradford TR, Rouse C, Irani AM, Rasp G, Van der Zwan JK, Van del Linden PW Development of a new, more sensitive immunoassay for human tryptase use in systemic anaphylaxis. J Clin Immunol 1994 14 190-204. 

Simons FER. Gu X. Johnston L. Simons KJ Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis Pediatrics 2000 106 1040-1044. 

The most frequent adverse effect associated with TIV is soreness at the injection site that lasts for less than 48 hours. TIV may cause fever and malaise in those who have not previously been exposed to the viral antigens in the vaccine. Allergic-type reactions (hives, systemic anaphylaxis) rarely occur after influenza vaccination and are likely a result of a reaction to residual egg protein in the vaccine. 

The PCA and ASA assays are performed in similar fashion, except that instead of using dye leakage as an indicator in the challenge phase, these studies attempt to produce skin lesions and systemic anaphylaxis, respectively, as experimental endpoints [55],... 

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