Anaphylactic response

This chapter highlights the mechanisms responsible for mast cell activation during anaphylactic responses to environmental substances. In addition to discussing in detail the activation of mast cells and basophils by IgE and antigen, we also will describe how mouse models have been used to analyze the importance of various proteins, cells, mediators and activation mechanisms in the expression of anaphylaxis in that species. 

Baba Y Nishida K, Fujii Y Hirano X Hikida M, Kurosaki X Essential function for the calcium sensor SXIMl in mast cell activation and anaphylactic responses. Nat Immunol 2008 9 81-88. 

Vennekens R, Olausson J, Meissner M, Bloch W, Mathar I, Philipp SE, Schmitz F, Weissgerber R Nilius B, Flockerzi V, Freichel M Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel XRPM4. Nat Immunol 2007 8 312-320. Guo Z, Xurner C, Castle D Relocation of the t-SNARE SNAP-23 from lamellipodia-like cell surface projections regulates compound exocytosis in mast cells. Cell 1998 94 537-548. 

I immediate Soluble Clonal expansion B cells Cyto-philic antibody (IgE) generated binds to mast cells Antigen binds to cell bound antibody crosslinks receptors, causing release of mediators Anaphylactic response to bee sting immediate response in allergic asthma... 

At high dose, potential for an anaphylactic response (not seen in mice). Also look for neutrophil proliferation. 

To prevent severe anaphylactic responses, administration of a small volume (10-20 ml) of low molecular mass dextran (Dextran 1) is often undertaken immediately prior to infusion of the higher molecular mass product. Circulatory anti-dextran antibodies will be mopped up by binding to the lower molecular mass dextran. This prevents formation of high molecular mass dextran-immune complexes/precipitates which often underseore the severe anaphylactic response. 

Akiyama, H., K. Hoshino, M. Tokuzumi, R. Teshima, H. Mori, T. Inakuma, Y. Ishiguro, Y. Coda, J. I. Sawada, and M. Toyoda. The effect of feeding carrots on immunoglobulin E production and anaphylactic response in mice. Biol Pharm Bull 1999 22(6) 551-555. 

Anaphylactic response. Seed oil, administered periodontally to adults, was effective. A 46-year-old male developed recurrent reaction to sesame seed oil. The symptoms were chills, shakiness, cramps, vomiting, fecal incontinence, fainting, flushing, and pruritic welts. Skin test revealed a four-plus multitest response and a marginally positive rast. Significant histamine release was also... 

Risk of convulsions Increased risk of anaphylactic response and bronchospasm Impaired stress response Especially in ICU patients... 

Immunologic reactions to drugs resulting in serum sickness are more common than immediate anaphylactic responses, but type II and type III hypersensitivities often overlap. The clinical features of serum sickness include urticarial and erythematous skin eruptions, arthralgia or arthritis, lymphadenopathy, glomerulonephritis, peripheral edema, and fever. The reactions generally last... 

I Clonal expansion of B Antigen binds to cell Anaphylactic response to... 

The molecular weight of bivalirudin is smaller than that of hirudin. Therefore, it is unlikely to cause anaphylactic responses however, bivalirudin has been reported to show cross-reactivity to anti-lepirudin antibodies. Caution is required when administering bivalirudin to patients previously treated with lepirudin (60),... 

Acute inhalation LC50 and oral and dermal LD50 studies suggest that female animals are more sensitive to the lethal effects of chromium(VI) compounds (see Sections 2.2.1.1, 2.2.2.1, and 2.2.3.1). Whether human females are more sensitive than males to toxic effects of chromium or its compounds is not known. Other information identifying possible susceptible populations was not located. Some individuals who are sensitive to chromium may develop asthma as an anaphylactic response to inhaled chromium. Also, some individuals have less ability than others to reduce chromium(VI) in the bloodstream and are more likely to be affected by the adverse effects of chromium exposure (Korallus 1986a, 1986b). The ability to reduce chromium(VI) in the bloodstream may be related to the ascorbic levels in the plasma. 

Fab (50 kd) and scFv (27 kd) antibody fragments have shorter plasma half-lives (0.5 to 21 hours) because of more rapid glomerular filtration and clearance [7], Plasma clearance, particularly of the xenogenic (usually mouse) portions of humanized and/or chimeric monoclonal antibodies, might be accelerated by development of anti-mouse (or other species), anti-isotypic, anti-idiotypic, or anti-allotypic antibodies that foster immune complex formation or reticuloendothelial clearance via several different FcR forms or elicit allergic or anaphylactic responses [7,8]. 

The immune response could also alter the pharmacokinetic or pharmacodynamic effects. Anaphylactic responses tested in the guinea pig, at any rate, are not predictive for humans and therefore not necessary. The same holds true for the standard testing batteries for immunotoxicity, these are not recommended. 

The induction of antibodies in animal studies does not predict their formation in humans. Humans developing antibodies against humanized proteins do not predict the loss of the therapeutic activity. In addition, the occurrence of severe anaphylactic responses to recombinant proteins is rare in humans. Therefore, the result of guinea pig tests for anaphylaxis is of little value for the evaluation of these products. 

Inhibitors of factor VIII are the most common and develop in 5-15% of patients with hemophilia A. Inhibitors of factor IX develop in 1 % of patients with hemophilia B (11,12). Patients with hemophiha B with complete gene deletions or derangement of the factor IX gene are particularly at risk of developing antibodies after the administration of factor IX concentrate (8). In patients with hemophilia B with antibodies, treatment with factor IX concentrate can result in an anaphylactic response. 

Thorland EC, Drost JB, Lusher JM, Warrier I, Shapiro A, Koerper MA, Dimichele D, Westman J, Key NS, Sommer SS. Anaphylactic response to factor IX replacement therapy in haemophilia B patients complete gene deletions confer the highest risk. Haemophiha 1999 5(2) 101-5. 

Omalizumab is the first anti-IgE antibody approved for the treatment of asthma not well controlled on high doses of ICSs. Omalizumab is a composite of 95% human and 5% antihuman murine IgE sequences. The mouse protein becomes part of the receptor complex and thus is shielded from exposure to the immune system and presents a low risk for an anaphylactic response. ... 

PAF receptor Reduced anaphylactic response to antigens. Intact endotoxin shock response... 

Ishii, S., Kuwaki, T., Nagase, T., Maki, K., Tashiro, F., Sunaga, S., Cao, W. H., Kume, K., Fukuchi, Y., Ikuta, K., Miyazaki, J. I., Kumada, M., and Shimizu, T. (1988). Imparied anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor. J. Exp. Med. 187, 1779-1788. 

PAF is also a lipid mediator of anaphylactic responses. PAF produced by anti-IgE challenge of IgE-sensitized basophils results in degranulation and histamine release. PAF can induce rapid and shallow breathing, transient apnea, and edema in the respiratory system. In the cardiovascular system, PAF directly induces bradycardia, hypotension, elevated right ventricular pressure, vascular spasms, and increased vascular permeability. 

Anaphylactic Response After Inhalation Exposure. There was one case of anaphylaxis reported in a paramedic who inhaled strontium-containing smoke in an enclosed space (Federman and Sachter 1997 see... 

Hypersensitivity. Hypersensitivity reactions, considered to be vaccine-related based on the timing and specificity of the reactions, were reported to the United States Vaccine Adverse Event Reporting System (VAERS) following vaccination for Lyme disease and subsequently evaluated (Burmester et al., 1995 Lathrop et al., 2002). Other reported immune system-related events to vaccines included rheumatoid arthritis, immune system disorders, detection of antinuclear antibodies, lupus syndrome, and lymphocytosis (Zhou et al., 2003). These were very rare events, with each condition comprising 0.2% or fewer of the total reports. Anaphylactic responses to vaccines were also rare and were estimated at less than one case per miUion administered vaccine doses (Bohlke et al., 2003). A number of studies evaluated anaphylactic responses to the measles-mumps-rubella (MMR), hepatitis B, diphtheria or tetanus vaccines with similar findings (Dobson et al., 1995 D Souza et al., 2000 Patja et al, 2000 Pool et al., 2002). However, some of the vaccine-induced hypersensitivity reactions are attributed to components of the formulation, such as gelatin or egg, rather than the antigen itself (Patja et al., 2001 Pool et al., 2002). 

It is of interest how the presently accepted concept of aspirin and aspirinlike compounds involvement with PGs came about. The last of the aspirin theories to arise proposed that aspirin interfered with leukocyte migration to the site of injury, thus inhibiting the inflammatory process. A prostaglandin phase of inflammation, where PGs arose in the exudate of experimentally induced edema after the appearance of histamine and bradykinin, was already known. These two events appeared to coincide in the inflammatory process. Thus, the time was ripe. In studying the mediators responsible for the anaphylactic response in sensitized guinea pig lungs, Piper and Vane (1969) isolated histamine, SRS-A, and a new substance they called rabbit aorta contracting substance (RCS), a very unstable material (1 to 2 min) whose release, and presumably production, was selectively inhibited by aspirin-... 

Anaphylactic responses have been reported in 10 to 30% of patients treated with the pladnum complexes. Symptoms, including facial edema, bronchoconstric-tion, hypotension, and tachycardia, occur within minutes of drug administration in padents previously exposed to the pladnum complexes. The incidence of hypersensitivity increases with increasing courses of platinum therapy. There appears to be cross-reactivity among the platinum complexes in that padents reactive to cispladn have a much higher incidence of hypersensitivity to carboplatin than do previously non-treated padents. 

---