Table 1. Roles (or potential roles) of various antibodies, effector cells and mediators in anaphylaxis in humans and mice.

Effector mechanisms		Humans	Mice
Antibody isotypes	IgE	- Elevated IgE levels in individuals with allergic diseases16, 19 - Purified IgE can transfer skin reactivity from a sensitized human subject to a naive host17, 21-23 - The anti-IgE Ab omalizumab can decrease the risks of anaphylaxis30-35	- PCA and PSA induced by transfer of antigen-specific IgE into naïve mice and challenge with the antigen24, 25 - IgE-mediated PCA and PSA is abrogated in mice lacking the high affinity IgE receptor FcεRI25 - ASA partially reduced in IgE-deficient or Fceε1-/- mice in some models, but not in others53, 89, 93, 103, 192, 193
	IgG	- No definitive evidence to date - Cases of anaphylaxis reported following treatment with therapeutic mAbs without detectable levels of anti-drug IgE58, 194-196	- IgG1, IgG2a and IgG2b (but not IgG3) can induce PSA50-60 - IgG-PSA is reduced in FcγRIII-/- mice51, 52 - IgG1- and IgG2b- (but not IgG2a-) PSA is enhanced in FcγRIIB-/- mice52 - Mice deficient in FcεRIα exhibit enhanced systemic anaphylaxis upon challenge with 2.4G2 anti-FcγRII/III Abs20 - Mice deficient for IgG1 or FcγRIII are largely protected in several ASA models89, 102, 103 - ‘Humanized’ mice expressing human FcγRI or FcγRIIA can develop IgG-mediated anaphylaxis150, 151, 153
Complement	Anaphylatoxins	- Injection of low doses of C3a, C4a or C5a in the skin of healthy volunteers induces immediate wheal and flare reactions66-69 - Blood levels of C3a, C4a and C5a correlate with the severity of anaphylaxis in humans65	- Reduced peanut-induced anaphylaxis in C4-/- mice197 - Reduced IgE-PCA in mice in which mast cells lack C3aR or C5aR198 - Anaphylaxis induced by direct activation of complement by peanut extract in one model177 - C3-/- mice can fully develop IgG-PSA model199 - ASA is not affected in C2-, C5- and C5aR-deficient mice, or after depletion of complement using cobra venom factor192, 200
Effector cells	Mast cells	- Elevated levels of tryptase have been detected during acute anaphylaxis in humans65, 79-82 - High occurrence of anaphylaxis in patients with mastocytosis85-87	- IgE-PCA and PSA markedly reduced in various strains of mast cell-deficient mice26-28, 58, 88 - ASA reduced in mast cell-deficient mice in some studies, but not in others51, 54, 89-93, 103, 192, 201
	Basophils	- No definitive evidence to date - “basophil activation tests” used to diagnose or confirm allergen sensitization96-99	- Controversial: some reports indicate a contribution of basophils to IgG-PSA52, 54, 56 or ASA53, 89, 91, while others found no significant role for basophils52, 92, 103, 199, 202
	Neutrophils	- MPO levels are increased in patients with anaphylaxis as compared to healthy donors106	- Antibody-mediated neutrophil depletion reduces IgG-PSA and ASA in some52, 53, 56 but not all91, 103 models
	Monocytes/ macrophages	- Not yet determined	- Depletion of monocytes/macrophages using clodronate liposomes can reduce IgG-PSA and ASA52, 89, 92, 102, 103
	Platelets	- No definitive evidence to date - Anaphylaxis in humans is associated with platelet activation108	- No definitive evidence to date - Depletion of platelets with anti-platelet antibodies (daily for 3 days) or neuraminidase does not reduce ASA102
Mediators	Histamine	- Aerosol administration of histamine induces bronchoconstriction in healthy volunteers114, 115 - Intravenous administration of histamine in volunteers can reproduce many of the symptoms of anaphylaxis116, 117 - H1 antihistamines are commonly used as adjunctive therapy for acute anaphylaxis and anaphylactoid reactions119	- Histamine injection induces anaphylaxis203, 204 - H1 antihistamine reduces IgE-PSA203 - IgG-PSA and ASA are reduced in mice pre-treated with H1 antihistamine in some models52, 103, 205, but not in others53, 102 - Mice deficient for the histidine decarboxylase (HDC)gene are protected from IgE-PSA203 - H1R- and H2R-deficient mice are partially protected from IgE-PSA204
	Cysteinyl leukotrienes (CysLTs)	- Levels of some CysLTs are increased during the onset of anaphylaxis131-133 - Intradermal injection of leukotriene B4 (LTB4), LTC4 and LTD4 induces a wheal and flare reaction in healthy volunteers134 - Aerosol administration of LTC4 and LTD4 in healthy subjects induces bronchoconstriction114, 115, 129	- Reduced IgE-PSA in mice deficient for LTC4S135 - Mice deficient for CysLT1R also have significantly reduced IgE-PCA136
	PAF	- Injection of PAF in the skin of healthy volunteers induces wheal and flare reactions123-125 - Circulating PAF levels increase and circulating PAF-AH activity decreases in proportion to the severity of anaphylaxis65, 82, 128	- PAF is released during IgG-PSA and ASA53, 91 - Injection of PAF induces anaphylaxis206 - Reduced ASA in mice deficient for the PAF receptor (PAFR)207 - PAFR antagonists can partially reduce anaphylaxis in IgG-PSA and ASA models52, 53, 57, 58, 91, 102, 103
	Others	- Anaphylaxis induces increases in levels of many mediators which could potentially contribute (positively or negatively) to the clinical signs and symptoms. This includes various cytokines and chemokines, prostaglandins, tryptase, bradykinin, serotonin, etc.	- Mast cell-derived prostaglandin D2 (PGD2) can limit IgE-PCA and IgE-PSA185