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Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy
Open accessAbstract
Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as "misdirected" type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, and against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance, and survival, to challenge with reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice surviving an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcεRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances.
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TL;DR
This review argues that mast cells and IgE, best known for allergic pathology, can also enhance innate and acquired resistance to animal venoms in mice. It synthesizes evidence that mast-cell proteases detoxify some venom components and that IgE/FcεRI/mast-cell responses can protect against honeybee and Russell’s viper venom, while noting unresolved questions.
Key findings
- Mast cells can enhance innate resistance to venoms from 4 species of poisonous snakes, the Gila monster, 2 scorpions, and the honeybee; mast-cell CPA3 detoxifies ET-1/sarafotoxin 6b, and chymase mMCP4 detoxifies VIP/helodermin and Gila monster/scorpion venoms. Human mast cell tryptase also reduced toxicity of venoms from six poisonous snakes in embryonic zebrafish assays.
- Acquired type 2 immune responses to honeybee venom or Russell’s viper venom increase survival against otherwise lethal challenge; resistance was transferable with 250 µL of immune serum, lost after IgE depletion by anti-IgE or heating at 56°C for 1 hour, and absent in IgE-deficient or FcεRI-deficient mice.
- Local IgE plus antigen (DNP-HSA) increased resistance to Russell’s viper venom admixed with DNP-HSA in C57BL/6 and BALB/c mice, whereas anti-DNP IgG1 or IgG2b did not protect and increased early hypothermia.
- Historical guinea pig studies showed anti-basophil serum ablated acquired resistance to *Amblyomma americanum* tick feeding; later mouse studies implicated mast cells, basophils, and IgE in acquired immunity to *Haemaphysalis longicornis*, with basophils possibly more important for *Dermacentor variabilis*.
Methods
- Narrative review, not a primary experimental report; it synthesizes prior studies from the authors and others.
- Evidence base includes mouse genetic models: mast cell-deficient/knock-in mice (WBB6F1-KitW/KitW-v, C57BL/6-KitW-sh/KitW-sh, C57BL/6-Cpa3-Cre+-Mcl-1fl/fl), IgE-deficient and FcεRI-deficient mice, protease-deficient or catalytically inactive CPA3 mice, passive serum transfer, venom challenge, and local IgE sensitization.
- Also cites in vitro embryonic zebrafish assays for human mast cell proteases and historical guinea pig basophil-depletion studies.
Limitations
- Stated: many unresolved questions remain, including whether mechanisms beyond protease release contribute, how venoms induce Th2/IgE responses, the evolutionary importance of ectoparasites/helminths/venomous animals, whether basophils contribute to venom resistance, and why some subjects develop fatal anaphylaxis rather than protection.
- Stated: proving that IgE, mast cells, or basophils dramatically influence survival of parasite-infected animals is challenging; prior parasite studies generally did not analyze overall survival or reproductive success, and some findings suggest effects may favor the parasite.
- Stated/evident: mouse model caveats—each mast cell/basophil deficiency model has features that must be considered, roles may vary by model strength and strain background, and the authors recommend using more than one genetic model; most venom-protection evidence is in mice, with human relevance largely inferential.
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Claims the paper makes
43 Check pending · 26 No full text of the sources · 12 Own interpretation · 6 Not checked yet · 1 Own result
In the paper
“We also found that genetically IgE-deficient mice [97] could not develop acquired immunity to honeybee venom, even though they developed a robust IgG1 antibody response to the venom [96].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked — no full text of the sourcecites [97] Oettgen HC, Martin TR, Wynshaw-Boris A, Deng C, Drazen JM, Leder P. Active anaphylaxis in IgE-deficient mice. Nature. 1994;370:367–70. source
- Check pendingcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, when such “immune serum” was depleted of IgE (either by adding a neutralizing antibody to IgE [35, 101] or by heating to 56° C for 1 hour, which eliminates the ability of IgE to bind to FcεRI and induce passive cutaneous anaphylaxis [102] while the function of other antibody classes, including IgG1, is not affected [103]), the immune serum’s ability to transfer enhanced resistance to”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [35] Amiri P, Haak-Frendscho M, Robbins K, McKerrow JH, Stewart T, Jardieu P. Anti-immunoglobulin E treatment decreases worm burden and egg production in schistosoma mansoni-infected normal and interferon gamma knockout mice. J Exp Med. 1994;180:43–51. source
- Check pendingcites [101] Haak-Frendscho M, Saban R, Shields RL, Jardieu PM. Anti-immunoglobulin E antibody treatment blocks histamine release and tissue contraction in sensitized mice. Immunology. 1998;94:115–21. source
- Not checked — no full text of the sourcecites [102] Prouvost-Danon A, Binaghi RA, Abadie A. Effect of heating at 56 degrees C on mouse IgE antibodies. Immunochemistry. 1977;14:81–4. source
- Check pendingcites [103] Strait RT, Morris SC, Finkelman FD. IgG-blocking antibodies inhibit IgE-mediated anaphylaxis in vivo through both antigen interception and FcγRIIb cross-linking. J Clin Invest. 2006;116:833–41. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“we will describe evidence that mast cells can enhance innate resistance, and survival, to challenge with reptile or arthropod venoms during a first exposure to such venoms.”
- Also stated in: § Identifying a beneficial role for mast cells in enhancing innate resistance to venoms. · hedged
“our initial evidence indicated that mast cells can increase the innate resistance of mice upon their first exposure to the venoms of 3 species of poisonous snakes, the Gila monster, the honeybee, or two especially dangerous scorpions.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Abstract
What the sources say
- Not checked — no full text of the sourcecites [15] Metz M, Piliponsky AM, Chen CC, Lammel V, Abrink M, Pejler G, et al. Mast cells can enhance resistance to snake and honeybee venoms. Science. 2006;313:526–30. source
- Check pendingcites [18] Akahoshi M, Song CH, Piliponsky AM, Metz M, Guzzetta A, Abrink M, et al. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice. J Clin Invest. 2011;121:4180–91. source
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- Also stated in: § Identifying a beneficial role for mast cells in enhancing innate resistance to venoms. · hedged
In the paper
“We found that most or all of the acquired resistance induced in mice by a single exposure to honeybee venom was transferable to naïve mice with only 250 microliters of serum from honeybee venom-immunized mice [96].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked yetcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“in mice surviving an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcεRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell’s”
- Also stated in: § Abstract · plain
“high affinity IgE receptor (FcεRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell’s viper venom.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Abstract
What the sources say
- Check pendingcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
- Check pendingcites [105] Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, et al. IgE antibodies, FcεRIα and IgE-mediated local anaphylaxis can limit snake venom toxicity. J Allergy Clin Immunol. 2016;137:246–57. source
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“We also showed that “immune serum” from WT mice could passively transfer enhanced resistance to honeybee venom to naïve IgE-deficient mice, unless such “immune serum” was first treated to neutralize IgE or impair its ability to bind to FcεRI [96].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Finally, we showed that such “immune serum” failed to transfer enhanced venom resistance to mice lacking either the IgE antibody-binding α chain of the FcεRI or the γ chain of FcεRI that is necessary for signaling initiated by aggregation of the receptor [5, 6].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked — no full text of the sourcecites [5] Kinet JP. The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annu Rev Immunol. 1999;17:931–72. source
- Check pendingcites [6] Rivera J, Fierro NA, Olivera A, Suzuki R. New insights on mast cell activation via the high affinity receptor for IgE. Adv Immunol. 2008;98:85–120. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Our evidence showed that IgE antibodies were the critical elements of the acquired host resistance to honeybee or Russell’s viper venom.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked yetcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that, in mice, IgE-associated type 2 immune responses against honeybee venom or Russell’s viper venom were able to increase significantly host resistance to challenge with potentially lethal doses of those venoms [96].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked yetcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“However, pre-sensitization of C57BL/6 mice with anti-DNP IgG1 or IgG2b, DNP-specific IgG isotypes with the capacity to activate effector cells via Fcγ receptors [108], not only failed to increase protection but also resulted in increased hypothermia at early time points compared to vehicle-treated or IgE-sensitized mice (Fig 7, B) [105].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [105] Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, et al. IgE antibodies, FcεRIα and IgE-mediated local anaphylaxis can limit snake venom toxicity. J Allergy Clin Immunol. 2016;137:246–57. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“However, pre-sensitization of C57BL/6 mice with anti-DNP IgG1 or IgG2b, DNP-specific IgG isotypes with the capacity to activate effector cells via Fcγ receptors [108], not only failed to increase protection but also resulted in increased hypothermia at early time points compared to vehicle-treated or IgE-sensitized mice (Fig 7, B) [105].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [105] Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, et al. IgE antibodies, FcεRIα and IgE-mediated local anaphylaxis can limit snake venom toxicity. J Allergy Clin Immunol. 2016;137:246–57. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Finally, we revealed that naïve genetically mast cell-deficient C57BL/6-KitW-sh/KitW-sh or C57BL/6-Cpa3-Cre+-Mcl-1fl/fl mice which received immune serum from honeybee venom-immunized C57BL/6 WT mice actually exhibited worse survival after challenge with a high dose of honeybee venom than did mast cell-deficient mice which had received serum from PBS mock-immunized C57BL/6 WT mice [96].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Notably, two different types of genetically mast cell-deficient mice also exhibited significantly diminished innate resistance to the toxicity and lethality of RVV (Fig. 6, A–C, E and F), supporting Higginbotham’s hypothesis that mast cells can contribute to enhanced innate resistance to this venom [76].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked — no full text of the sourcecites [76] Higginbotham RD. Mast cells and local resistance to Russell’s viper venom. J Immunol. 1965;95:867–75. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Compared to the corresponding mast cell-sufficient mice, such naïve mast cell-deficient mice also exhibited many fewer attempts to scratch sites of RVV injection (Fig. 6, D and G).”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [105] Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, et al. IgE antibodies, FcεRIα and IgE-mediated local anaphylaxis can limit snake venom toxicity. J Allergy Clin Immunol. 2016;137:246–57. source
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that pre-sensitization with anti-DNP IgE significantly increased the resistance of C57BL/6 (Fig 7, B and C) or BALB/c (see Fig E5, H-I in the online repository of ref. [105]) mice to challenge with a potentially lethal amount of RVV admixed with DNP-HAS [105].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [105] Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, et al. IgE antibodies, FcεRIα and IgE-mediated local anaphylaxis can limit snake venom toxicity. J Allergy Clin Immunol. 2016;137:246–57. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It should be noted, however, that it has been challenging to prove that IgE, mast cells or basophils dramatically influence the survival of parasite-infected animals.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Possible beneficial functions of mast cells, basophils and IgE.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“It also was known that tick feeding sites in sensitized guinea pigs contained large numbers of basophils and eosinophils [50].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [50] Allen JR. Tick resistance: basophils in skin reactions of resistant guinea pigs. Int J Parasitol. 1973;3:195–200. source
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In the paper
“However, later work by our group, employing both pharmacological approaches and shRNA knock down of CPA3 in adoptively-transferred mast cells [15], as well as elegant studies by Schneider et al., who exploited a mouse they created which expressed only a catalytically inactive CPA3 [81], indicated that CPA3 is the key mast cell-derived protease that detoxifies both ET-1 and sarafotoxin 6b.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Not checked — no full text of the sourcecites [15] Metz M, Piliponsky AM, Chen CC, Lammel V, Abrink M, Pejler G, et al. Mast cells can enhance resistance to snake and honeybee venoms. Science. 2006;313:526–30. source
- Check pendingcites [81] Schneider LA, Schlenner SM, Feyerabend TB, Wunderlin M, Rodewald HR. Molecular mechanism of mast cell mediated innate defense against endothelin and snake venom sarafotoxin. J Exp Med. 2007;204:2629–39. source
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In the paper
“Within or among different mammalian species, individual mast cell subpopulations can very in their susceptibility to activation via these innate mechanisms, likely reflecting such factors as microenvironmentally regulated differences in levels of expression of the cognate receptors [14, 19].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Innate activation of mast cells.
What the sources say
- Not checked — no full text of the sourcecites [14] Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol. 2005;23:749–86. source
- Not checked yetcites [19] Galli SJ, Borregaard N, Wynn TA. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol. 2011;12:1035–44. source
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hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Depending on the mammalian species, mast cells can contain several tryptases and chymases of distinct substrate specificity, as well as CPA3 [13, 72, 83].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Check pendingcites [13] Douaiher J, Succar J, Lancerotto L, Gurish MF, Orgill DP, Hamilton MJ, et al. Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing. Adv Immunol. 2014;122:211–52. source
- Check pendingcites [72] Galli SJ, Tsai M, Marichal T, Tchougounova E, Reber LL, Pejler G. Approaches for analyzing the roles of mast cells and their proteases in vivo. Adv Immunol. 2015;126:45–127. source
- Not checked — no full text of the sourcecites [83] Wernersson S, Pejler G. Mast cell secretory granules: armed for battle. Nat Rev Immunol. 2014;14:478–94. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, a recent study of human mast cell-derived proteases shows that tryptase (rather than chymase or CPA3) is more important at reducing the toxicity of the venoms of six different poisonous snakes, when embryonic zebra fish are used to assess such toxicity in vitro [84].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Not checked yetcites [84] Anderson E, Stavenhagen K, Kolarich D, Sommerhoff CP, Maurer M, Metz M. Human mast cell tryptase is a potential treatment for snakebite envenoming across multiple snake species. Front Immunol. 2018;9:1532. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Administration of this ABS i.v. to guinea pigs sensitized to express “cutaneous basophil hypersensitivity” (CBH), an antigen-induced, delayed onset, erythematous skin reaction that contains large numbers of infiltrating basophils [44], revealed that ABS could be used to reduce markedly the numbers of basophils infiltrating the skin at such sites [43].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [43] Galli SJ, Colvin RB, Verderber E, Galli AS, Monahan R, Dvorak AM, et al. Preparation of a rabbit anti-guinea pig basophil serum: in vitro and in vivo characterization. J Immunol. 1978;121:1157–66. source
- Not checked — no full text of the sourcecites [44] Dvorak HF. Cutaneous basophil hypersensitivity. J Allergy Clin Immunol. 1976;58:229–40. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“One step in that direction was the finding that ET-1 can initiate a homeostatic mechanism whereby proteases released by mast cells activated by ET-1 can degrade that vasoactive peptide and thereby diminish its potential toxicity in vivo [65].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Not checked — no full text of the sourcecites [65] Maurer M, Wedemeyer J, Metz M, Piliponsky AM, Weller K, Chatterjea D, et al. Mast cells promote homeostasis by limiting endothelin-1-induced toxicity. Nature. 2004;432:512–6. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover,, the importance of particular mast cell (or basophil) roles in individual biological responses may vary both according to the details of the model used to study that biological response (e.g., whether one is studying a “weak” or “strong” model of that response) and based on the strain background of the mice.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > New models for analyzing the functions of basophils and mast cells.
What the sources say
- Check pendingcites [72] Galli SJ, Tsai M, Marichal T, Tchougounova E, Reber LL, Pejler G. Approaches for analyzing the roles of mast cells and their proteases in vivo. Adv Immunol. 2015;126:45–127. source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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A statement the paper makes itself — it cites no source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Abstract
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Notably, ABS treatment also essentially ablated the acquired resistance to tick feeding conferred by sensitization (Fig. 1) [45].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [45] Brown SJ, Galli SJ, Gleich GJ, Askenase PW. Ablation of immunity to amblyomma americanum by anti-basophil serum: cooperation between basophils and eosinophils in expression of immunity to ectoparasites (ticks) in guinea pigs. J Immunol. 1982;129:790–6. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“They also showed that mast cells developed in WBB6F1-W/Wv mice that had been engrafted with bone marrow cells from the WT (wild type) littermate WBB6F1-+/+ mice [56].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > “Mast cell knock-in mice”.
What the sources say
- Not checked — no full text of the sourcecites [56] Kitamura Y, Go S, Hatanaka K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood. 1978;52:447–52. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Using mast cell knock-in mice, Metz et al. also provided evidence that mast cells were important in substantially enhancing the innate resistance of mice to honeybee (Apis mellifera) venom and to the venoms of two North American pit vipers, the western diamondback rattlesnake (Crotalus atrox) and the southern copperhead (Agkistrodon contortrix contortrix) [15].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Not checked — no full text of the sourcecites [15] Metz M, Piliponsky AM, Chen CC, Lammel V, Abrink M, Pejler G, et al. Mast cells can enhance resistance to snake and honeybee venoms. Science. 2006;313:526–30. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, eventually, non-irradiated WBB6F1-W/Wv mice engrafted with sufficient (e.g., 1 × 107) WBB6F1-+/+ or other genetically-compatible WT whole bone marrow cells also undergo virtually complete replacement of multiple other hematopoietic lineages (including granulocytes and lymphocytes) with cells of donor origin [58–60].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > “Mast cell knock-in mice”.
What the sources say
- Not checked — no full text of the sourcecites [58] Harrison DE, Astle CM. Population of lymphoid tissues in cured W‑anemic mice by donor cells. Transplantation. 1976;22:42–6. source
- Check pendingcites [59] Nakano T, Waki N, Asai H, Kitamura Y. Lymphoid differentiation of the hematopoietic stem cell that reconstitutes total erythropoiesis of a genetically anemic W/Wv mouse. Blood. 1989;73:1175–9. source
- Check pendingcites [60] Nakano T, Waki N, Asai H, Kitamura Y. Different repopulation profile between erythroid and nonerythroid progenitor cells in genetically anemic W/Wv mice after bone marrow transplantation. Blood. 1989;74:1552–6. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“To our knowledge, this was the first in vivo experimental evidence that went beyond correlative and observational studies (i.e., demonstrating the presence of basophils at tick feeding sites) indicating that basophils might represent one important component of acquired, antibody-dependent resistance to the feeding of an arthropod.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [45] Brown SJ, Galli SJ, Gleich GJ, Askenase PW. Ablation of immunity to amblyomma americanum by anti-basophil serum: cooperation between basophils and eosinophils in expression of immunity to ectoparasites (ticks) in guinea pigs. J Immunol. 1982;129:790–6. source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“And some findings even suggest that, in certain settings, IgE or mast cells may have effects during host responses to parasites (e.g., effects which direclty or indirectly result in increased parasite egg production) that may favor the parasite rather than the host [34–36].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Possible beneficial functions of mast cells, basophils and IgE.
What the sources say
- Check pendingcites [34] Arizono N, Kasugai T, Yamada M, Okada M, Morimoto M, Tei H, et al. Infection of nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficient Ws/Ws rats. Blood. 1993;81:2572–8. source
- Check pendingcites [35] Amiri P, Haak-Frendscho M, Robbins K, McKerrow JH, Stewart T, Jardieu P. Anti-immunoglobulin E treatment decreases worm burden and egg production in schistosoma mansoni-infected normal and interferon gamma knockout mice. J Exp Med. 1994;180:43–51. source
- Not checked — no full text of the sourcecites [36] Newlands GF, Miller HR, MacKellar A, Galli SJ. Stem cell factor contributes to intestinal mucosal mast cell hyperplasia in rats infected with Nippostrongylus brasiliensis or Trichinella spiralis, but anti-stem cell factor treatment decreases parasite egg production during N brasiliensis infection. Blood. 1995;86:1968–76. source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“It is now generally accepted that mast cells and basophils can contribute importantly to the pathology associated with allergic disorders, including potentially fatal anaphylaxis [3, 22, 23].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Possible beneficial functions of mast cells, basophils and IgE.
What the sources say
- Not checked yetcites [3] Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18:693–704. source
- Not matchedcites [22] Portier MM, Richet C. De l’action anaphylactique de certains venims. C R Seances Soc Biol Fil. 1902;54:170–2.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [23] Finkelman FD. Anaphylaxis: lessons from mouse models. J Allergy Clin Immunol. 2007;120:506–15. source
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“Similar approaches were used to provide evidence that mast cells and mMCP4 can contribute to enhanced innate resistance of mice to the venoms of two scorpions, one from the old world, the Deathstalker (Leiurus quiquestriatus hebraeus), and one from the new world, the Arizona bark scorpion (Centruroides exilicauda) [18].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Check pendingcites [18] Akahoshi M, Song CH, Piliponsky AM, Metz M, Guzzetta A, Abrink M, et al. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice. J Clin Invest. 2011;121:4180–91. source
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, for at least some mast cell populations, PAMPs are more effective in eliciting release of cytokines and chemokines than granule-stored mediators [16, 17].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Innate activation of mast cells.
What the sources say
- Not checked — no full text of the sourcecites [16] Dawicki W, Marshall JS. New and emerging roles for mast cells in host defence. Curr Opin Immunol. 2007;19:31–8. source
- Check pendingcites [17] Abraham SN, St. John AL. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol. 2010;10:440–52. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“By contrast, it appears that basophils may have a more important role than mast cells in acquired resistance to the feeding of larval Dermacentor variabilis ticks in mice [53].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [53] Steeves EB, Allen JR. Basophils in skin reactions of mast cell-deficient mice infested with dermacentor variabilis. Int J Parasitol. 1990;20:655–67. source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, Tsai et al. showed that one also can generate such mast cells from embryonic stem cells, permitting the analysis in vivo of mast cells which lack products which, if absent in the germ line, would result in embryonic or perinatal lethality [64].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > “Mast cell knock-in mice”.
What the sources say
- Check pendingcites [64] Tsai M, Wedemeyer J, Ganiatsas S, Tam SY, Zon LI, Galli SJ. In vivo immunological function of mast cells derived from embryonic stem cells: an approach for the rapid analysis of even embryonic lethal mutations in adult mice in vivo. Proc Natl Acad Sci USA. 2000;97:9186–90. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“In some unfortunate people, such IgE responses to venoms put these individuals at risk to develop potentially fatal episodes of anaphylaxis [3, 7, 23, 94].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked yetcites [3] Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18:693–704. source
- Check pendingcites [7] Oettgen HC, Geha RS. IgE in asthma and atopy: cellular and molecular connections. J Clin Invest. 1999;104:829–35. source
- Not checked — no full text of the sourcecites [23] Finkelman FD. Anaphylaxis: lessons from mouse models. J Allergy Clin Immunol. 2007;120:506–15. source
- Not checked — no full text of the sourcecites [94] Bilo BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JN. Diagnosis of hymenoptera venom allergy. Allergy. 2005;60:1339–49. source
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“In such Th2 cell-associated “type 2” immune responses, IgE enables antigen-specific function of effector cells by binding to high affinity receptors for IgE (FcεRI) on the cells’ surface [5, 6].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Mast cells, basophils and IgE in the pathology of allergic disorders.
What the sources say
- Not checked — no full text of the sourcecites [5] Kinet JP. The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annu Rev Immunol. 1999;17:931–72. source
- Check pendingcites [6] Rivera J, Fierro NA, Olivera A, Suzuki R. New insights on mast cell activation via the high affinity receptor for IgE. Adv Immunol. 2008;98:85–120. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Galli et al. generated a rabbit anti-guinea pig basophil antiserum (ABS) and showed that intravenous (i.v.) administration of ABS markedly reduced numbers of blood basophils in vivo, without reducing numbers of blood eosinophils or the total white blood cell count, or changing numbers of intradermal mast cells [43].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [43] Galli SJ, Colvin RB, Verderber E, Galli AS, Monahan R, Dvorak AM, et al. Preparation of a rabbit anti-guinea pig basophil serum: in vitro and in vivo characterization. J Immunol. 1978;121:1157–66. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites.”
- Also stated in: § Possible beneficial functions of mast cells, basophils and IgE. · hedged
“A major hypothesis about the potential “beneficial functions” of such allergic effector mechanisms is that IgE-associated type 2 immune responses contribute to host defense against helminths and certain other parasites [4, 24–26].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Abstract
What the sources say
- Check pendingcites [4] Pulendran B, Artis D. New paradigms in type 2 immunity. Science. 2012;337:431–5. source
- Not checked — no full text of the sourcecites [24] Stetson DB, Voehringer D, Grogan JL, Xu M, Reinhardt RL, Scheu S, et al. Th2 cells: orchestrating barrier immunity. Adv Immunol. 2004;83:163–89. source
- Not checked — no full text of the sourcecites [25] Finkelman FD, Shea-Donohue T, Morris SC, Gildea L, Strait R, Madden KB, et al. Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunol Rev. 2004;201:139–55. source
- Not checked — no full text of the sourcecites [26] Fitzsimmons CM, Dunne DW. Survival of the fittest: allergology or parasitology? Trends Parasitol. 2009;25:447–51. source
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Possible beneficial functions of mast cells, basophils and IgE. · hedged
In the paper
“Using mast cell knock-in C57BL/6-KitW-sh/KitW-sh mice engrafted with ETA receptor-deficient or WT mast cells derived in vitro from ETA−/− or ETA−/+ embryonic stem cells, Maurer et al. found that mast cell activation by ET-1 via the ETA receptor contributed to this effect [65].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Not checked — no full text of the sourcecites [65] Maurer M, Wedemeyer J, Metz M, Piliponsky AM, Weller K, Chatterjea D, et al. Mast cells promote homeostasis by limiting endothelin-1-induced toxicity. Nature. 2004;432:512–6. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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A statement the paper makes itself — it cites no source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Observational and epidemiological studies in humans, as well as studies in experimental animals (including those employing mice genetically deficient in mast cells, basophils or IgE), strongly suggest that one beneficial role of IgE, mast cells and basophils is to help to defend the host against ectoparasites such as ticks”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings show that, in the tested mice, local tissue responses mediated by IgE and antigen can enhance host resistance against RVV even when that antigen is not a native constituent of the venom.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Also, there is abundant evidence that Th2 cell-mediated responses are subject to immune regulation which can diminish pathology related to IgE-dependent reactivity to the inducing antigen, including honeybee venom [114–116].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
What the sources say
- Not checked — no full text of the sourcecites [114] Muller UR. Bee venom allergy in beekeepers and their family memberws. Curr Opin Allergy Clin Immunol. 2005;5:343–7. source
- Check pendingcites [115] Meiler F, Zumkehr J, Klunker S, Ruckert B, Akdis CA, Akdis M. In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J Exp Med. 2008;205:2887–98. source
- Not checked — no full text of the sourcecites [116] Ozdemir C, Kucuksezer UC, Akdis M, Akdis CA. Mechanisms of immunotherapy to wasp and bee venom. Clin Exp Allergy. 2011;41:1226–34. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Taken together, these two initial studies [96, 104] support the hypothesis that one physiological function of IgE is to protect the host against noxious substances.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
- Check pendingcites [104] Palm NW, Rosenstein RK, Yu S, Schenten DD, Florsheim E, Medzhitov R. Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity. Immunity. 2013;39:976–85. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“As noted above, Palm et al. reported that immunization of mice with honeybee venom-derived bvPLA2, which represents approximately 10% of the dry weight of whole BV [106], can reduce the toxicity-related hypothermia induced by subsequent challenge with a high dose of the same allergen in an antibody- and FcεRIα-dependent manner [104].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [104] Palm NW, Rosenstein RK, Yu S, Schenten DD, Florsheim E, Medzhitov R. Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity. Immunity. 2013;39:976–85. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, evidence derived from in vitro studies with embryonic zebra fish shows that human mast cell tryptase (but not human mast cell chymase or CPA3), can markedly reduce the toxicity of the venoms of six different poisonous snakes [84].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
What the sources say
- Check pendingcites [84] Anderson E, Stavenhagen K, Kolarich D, Sommerhoff CP, Maurer M, Metz M. Human mast cell tryptase is a potential treatment for snakebite envenoming across multiple snake species. Front Immunol. 2018;9:1532. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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A statement the paper makes itself — it cites no source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and to diminish the numbers of parasites and burden of disease in mammals infected with certain helminths.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings are consistent with the general idea that the host needs only to generate an IgE response against a limited number of the components of a complex venom (perhaps as few as one component) in order to manifest enhanced acquired resistance to that venom.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“We used amounts of anti-DNP IgE and DNP-HSA that were able to induce a local increase in vascular permeability at the DNP-HSA injection site without resulting in systemic hypothermia, and showed that the amount of DNP-HSA we used did not, by itself, influence the toxicity of RVV (see Fig E5 in the Online Repository of ref. [105]).”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [105] Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, et al. IgE antibodies, FcεRIα and IgE-mediated local anaphylaxis can limit snake venom toxicity. J Allergy Clin Immunol. 2016;137:246–57. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Tissue resident cells with morphological, biochemical, and functional properties of mammalian mast cells, and which can produce histamine, heparin and serine proteases, are present in tunicates, whose ancestors appeared in evolution before the development of adaptive immunity [109, 110].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
What the sources say
- Not checked — no full text of the sourcecites [109] Cavalcante MC, de Andrade LR, Du Bocage Santos-Pinto C, Straus AH, Takahashi HK, Allodi S, et al. Colocalization of heparin and histamine in the intracellular granules of test cells from the invertebrate styela plicata (chordata-tunicata). J Struct Biol. 2002;137:313–21. source
- Check pendingcites [110] Wong GW, Zhuo L, Kimata K, Lam BK, Satoh N, Stevens RL. Ancient origin of mast cells. Biochem Biophys Res Commun. 2014;451:314–8. source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This allowed such tissue-resident (or, in the case of basophils, circulating) cells to become “immunologically primed” or “sensitized” to undergo activation for mediator release upon encountering relatively small amounts of the antigen identified by their surface-bound IgE antibodies.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After the appearance of acquired immunity and the development of antibodies, these ancient hematopoietic lineages acquired the ability to bind immunoglobulins such as IgE (in mammals) to their surface.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“This evidence supports the notion [39–41] that key elements of “allergic reactivity”, including mast cells and IgE, indeed can importantly enhance innate and acquired host resistance to venoms.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
What the sources say
- Not checked — no full text of the sourcecites [39] Profet M. The function of allergy: immunological defense against toxins. Q Rev Biol. 1991;66:23–62. source
- Not checked — no full text of the sourcecites [40] Stebbings JH Jr.. Immediate hypersensitivity: a defense against arthropods? Perspect Biol Med. 1974;17:233–9. source
- Check pendingcites [41] Palm NW, Rosenstein RK, Medzhitov R. Allergic host defences. Nature. 2012;484:465–72. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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A statement the paper makes itself — it cites no source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Evidence in mice indicates that mast cells can enhance innate resistance of mice to 4 species of poisonous snakes, the Gila monster, 2 species of scorpions, and the honeybee, and that mast cell proteases (specifically, CPA3 and the chymase MCP4) can contribute to such mast cell-dependent innate defenses by degrading toxins present in some of these venoms.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Evidence in mice indicates that mast cells can enhance innate resistance of mice to 4 species of poisonous snakes, the Gila monster, 2 species of scorpions, and the honeybee, and that mast cell proteases (specifically, CPA3 and the chymase MCP4) can contribute to such mast cell-dependent innate defenses by degrading toxins present in some of these venoms.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“In considering this question, it should be noted that many people who develop type 2 immune responses to BV do not exhibit anaphylactic reactivity despite having venom-specific IgE antibodies [113].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
What the sources say
- Not checked — no full text of the sourcecites [113] Antonicelli L, Bilo MB, Bonifazi F. Epidemiology of hymenoptera allergy. Curr Opin Allergy Clin Immunol. 2002;2:341–6. source
plain- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The latter finding supports the idea proposed both by Stebbings [40] and Profet [39] that elements of allergic responses, in this case, mast cells, can confer benefit to hosts experiencing attacks by arthropods [40] or other sources of toxins [39] by altering the host’s behavior in ways that would help to eliminate, or at least permit the host to become aware of, the threat.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked — no full text of the sourcecites [40] Stebbings JH Jr.. Immediate hypersensitivity: a defense against arthropods? Perspect Biol Med. 1974;17:233–9. source
- Not checked — no full text of the sourcecites [39] Profet M. The function of allergy: immunological defense against toxins. Q Rev Biol. 1991;66:23–62. source
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 23
- Probably not a substantial claim. 10
In the paper
“Our initial findings indicate that the propensity to develop protective vs. potentially harmful type 2 immune responses to venoms, at least in mice, can depend on the genetic background of the animal, the type and amount of venom to which the animal is exposed, and/or the frequency of such venom exposures [105].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
What the sources say
- Check pendingcites [105] Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, et al. IgE antibodies, FcεRIα and IgE-mediated local anaphylaxis can limit snake venom toxicity. J Allergy Clin Immunol. 2016;137:246–57. source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Subsequently, we found that the acquired enhanced resistance to Russell’s viper venom (RVV) which we observed in mice that had developed type 2 immune responses to that venom [96] also was highly dependent on IgE (Fig. 5) and FcεRI (see Fig. 4, A–E in ref. [105]), and could be effectively transferred by immune serum into normal mice (see Fig. 3, F–J in ref. [105]) but not into C57BL/6-Cpa3-Cre;Mcl”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [96] Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity. 2013;39:963–75. source
- Check pendingcites [105] Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, et al. IgE antibodies, FcεRIα and IgE-mediated local anaphylaxis can limit snake venom toxicity. J Allergy Clin Immunol. 2016;137:246–57. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A check of a cited source is scheduled, or we don’t hold its full text yet; the claim is checked once it runs.
In the paper
“FcεRI are expressed on mast cells, that reside in most vascularized tissues in mammals and other vertebrates, and on basophilic granulocytes (“basophils”), that ordinarily circulate in very low numbers in the blood but which can be recruited to sites of inflammation [3, 5–10].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Mast cells, basophils and IgE in the pathology of allergic disorders.
What the sources say
- Not checked yetcites [3] Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18:693–704. source
A check is scheduled.
- Not checked — no full text of the sourcecites [5] Kinet JP. The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annu Rev Immunol. 1999;17:931–72. source
- Check pendingcites [6] Rivera J, Fierro NA, Olivera A, Suzuki R. New insights on mast cell activation via the high affinity receptor for IgE. Adv Immunol. 2008;98:85–120. source
- Check pendingcites [7] Oettgen HC, Geha RS. IgE in asthma and atopy: cellular and molecular connections. J Clin Invest. 1999;104:829–35. source
- Not checked — no full text of the sourcecites [8] Karasuyama H, Mukai K, Obata K, Tsujimura Y, Wada T. Nonredundant roles of basophils in immunity. Annu Rev Immunol. 2011;29:45–69. source
- Check pendingcites [9] Sullivan BM, Liang HE, Bando JK, Wu D, Cheng LE, McKerrow JK, et al. Genetic analysis of basophil function in vivo. Nat Immunol. 2011;12:527–35. source
- Not checked — no full text of the sourcecites [10] Voehringer D. Protective and pathological roles of mast cells and basophils. Nat Rev Immunol. 2013;13:362–75. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Not checked yet
In the paper
“Even before Profet’s 1991 paper, James Stebbings, Jr. hypothesized that “a major function of the immediate hypersensitivity reactions has been the protection of terrestrial vertebrates from the bites of, or invasion by, arthropods” [40].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Possible beneficial functions of mast cells, basophils and IgE.
What the sources say
- Not checked — no full text of the sourcecites [40] Stebbings JH Jr.. Immediate hypersensitivity: a defense against arthropods? Perspect Biol Med. 1974;17:233–9. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By undergoing degranulation and releasing proteases that can inactivate potentially toxic endogenous peptides or peptides in venoms, mouse mast cells can help to restore homeostasis, albeit while also enhancing features of the ensuing local and perhaps systemic inflammatory responses.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Such envenomation not only provokes an innate inflammatory response and pathology related to the biological activities of the venoms’ toxins [86–88], but also can induce allergic sensitization associated with the development of specific IgE antibodies [89–94].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked — no full text of the sourcecites [86] Habermann E. Bee and wasp venoms. Science. 1972;177:314–22. source
- Not checked — no full text of the sourcecites [87] Mukherjee AK, Ghosal SK, Maity CR. Some biochemical properties of Russell’s viper (daboia russelli) venom from eastern India: correlation with clinico-pathological manifestation in Russell’s viper bite. Toxicon. 2000;38:163–75. source
- Not checked — no full text of the sourcecites [88] Risch M, Georgieva D, von Bergen M, Jehmlich N, Genov N, Arni RK, et al. Snake venomics of the siamese Russell’s viper (daboia russelli siamensis)—relation to pharmacological activities. J Proteomics. 2009;72:256–69. source
- Not checked — no full text of the sourcecites [89] Saelinger CB, Higginbotham RD. Hypersensitivity responses to bee venom and the mellitin. Int Arch Allergy Appl Immunol. 1974;46:28–37. source
- Not checked — no full text of the sourcecites [90] Charavejasarn CC, Reisman RE, Arbesman CE. Reactions of anti-bee venom mouse reagins and other antibodies with related antigens. Int Arch Allergy Appl Immunol. 1975;48:691–7. source
- Not checked — no full text of the sourcecites [91] Jarisch R, Yman L, Boltz A, Sandor I, Janitsch A. IgE antibodies to bee venom, phospholipase A, melittin and wasp venom. Clin Allergy. 1979;9:535–41. source
- Check pendingcites [92] Wadee AA, Rabson AR. Development of specific IgE antibodies after repeated exposure to snake venom. J Allergy Clin Immunol. 1987;80:695–8. source
- Not checked — no full text of the sourcecites [93] Annila I. Bee venom allergy. Clin Exp Allergy. 2000;30:1682–7. source
- Not checked — no full text of the sourcecites [94] Bilo BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JN. Diagnosis of hymenoptera venom allergy. Allergy. 2005;60:1339–49. source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It was known that when guinea pigs subjected to a single round of exposure to the feeding of larval A. americanum ticks are challenged with a second exposure to the larval ticks about a month later, tick feeding success is markedly diminished, and such acquired resistance can be transferred by administering serum from sensitized to naïve guinea pigs [49].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [49] Brown SJ, Askenase PW. Cutaneous basophil responses and immune resistance of guinea pigs to ticks: passive transfer with peritoneal exudate cells or serum. J Immunol. 1981;127:2163–7. source
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Basophils activated via FcεRI aggregation can release a panel of mediators partially overlapping with those of mast cells, but, as compared to mast cells, they contain much lower amounts of proteases and appear to produce fewer cytokines and chemokines [8–10].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Mast cells, basophils and IgE in the pathology of allergic disorders.
What the sources say
- Not checked — no full text of the sourcecites [8] Karasuyama H, Mukai K, Obata K, Tsujimura Y, Wada T. Nonredundant roles of basophils in immunity. Annu Rev Immunol. 2011;29:45–69. source
- Check pendingcites [9] Sullivan BM, Liang HE, Bando JK, Wu D, Cheng LE, McKerrow JK, et al. Genetic analysis of basophil function in vivo. Nat Immunol. 2011;12:527–35. source
- Not checked — no full text of the sourcecites [10] Voehringer D. Protective and pathological roles of mast cells and basophils. Nat Rev Immunol. 2013;13:362–75. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A statement the paper makes itself — it cites no source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mouse mast cells contain at least two different proteases, CPA3 and chymase (mMCP4), which permit such mast cells to respond, after their activation via cognate receptors that can bind either the endogenous or the structurally similar reptile-derived peptides, to high and potentially toxic levels of ET-1 and VIP, respectively.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Profet proposed that acute allergic reactions, manifested as immediately occurring symptoms in response to allergen exposure, such as sneezing, coughing, vomiting and diarrhea, evolved as defense mechanisms allowing the sensitized host to respond immediately to, and to expel, neutralize and/or avoid, noxious substances which might be indicative of potentially life-threatening situations [39].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Possible beneficial functions of mast cells, basophils and IgE.
What the sources say
- Not checked — no full text of the sourcecites [39] Profet M. The function of allergy: immunological defense against toxins. Q Rev Biol. 1991;66:23–62. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Early work by Higginbotham and colleagues suggested that mast cells might be able to diminish the toxicity of certain venoms by degranulating and releasing heparin in response to venom exposure [76, 77].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Not checked — no full text of the sourcecites [76] Higginbotham RD. Mast cells and local resistance to Russell’s viper venom. J Immunol. 1965;95:867–75. source
- Not checked — no full text of the sourcecites [77] Higginbotham RD, Karnella S. The significance of the mast cell response to bee venom. J Immunol. 1971;106:233–40. source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“However, the recipient W/Wv mice also were cured of their anemia [56], as was initially shown by Elizabeth Russell [57].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > “Mast cell knock-in mice”.
What the sources say
- Not checked — no full text of the sourcecites [56] Kitamura Y, Go S, Hatanaka K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood. 1978;52:447–52. source
- Not checked — no full text of the sourcecites [57] Russell ES. Hereditary anemias of the mouse: a review for geneticists. Adv Genet. 1979;20:357–459. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Hiroshi Matsuda and Yukihiko Kitamura and colleagues (using mast cell-engrafted genetically mast cell deficient (WB/Re-W/+ X C57BL/6-Wv/+)F1-”W/Wv” mice) [51], and Hajime Karasuyama and colleagues (using mice genetically deficient in basophils [52]), provided evidence that both mast cells and basophils, as well as IgE, can contribute to acquired immunity to the feeding of Haemaphysalis longicornis”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [51] Matsuda H, Watanabe N, Kiso Y, Hirota S, Ushio H, Kannan Y, et al. Necessity of IgE antibodies and mast cells for manifestation of resistance against larval haemaphysalis longicornis ticks in mice. J Immunol. 1990;144:259–62. source
- Check pendingcites [52] Wada T, Ishiwata K, Koseki H, Ishikura T, Ugajin T, Ohnuma N, et al. Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. J Clin Invest. 2010;120:2867–75. source
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Treatment with rabbit AES had a lesser, but still statistically significant, effect on tick feeding success, whereas normal rabbit serum was without effect (Fig. 1) [45].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [45] Brown SJ, Galli SJ, Gleich GJ, Askenase PW. Ablation of immunity to amblyomma americanum by anti-basophil serum: cooperation between basophils and eosinophils in expression of immunity to ectoparasites (ticks) in guinea pigs. J Immunol. 1982;129:790–6. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“We recently showed that this approach also can be pursued using C57BL/6-Cpa3-Cre+-Mcl-1fl/fl mice, which are mast cell-deficient (and also have substantially diminished numbers and function of basophils) due to the lineage-restricted ablation of the anti-apoptotic factor, myeloid cell leukemia 1 (Mcl-1), in lineages with sufficiently high expression of the Cpa3 gene [70].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > “Mast cell knock-in mice”.
What the sources say
- Check pendingcites [70] Lilla JN, Chen CC, Mukai K, BenBarak MJ, Franco CB, Kalesnikoff J, et al. Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl‑1fl/fl mice. Blood. 2011;118:6930–8. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ABS did cause a reduction in skin mast cell numbers if injected intra-dermally, raising the possibility that the antiserum targeted an antigen shared by basophils and mast cells.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [43] Galli SJ, Colvin RB, Verderber E, Galli AS, Monahan R, Dvorak AM, et al. Preparation of a rabbit anti-guinea pig basophil serum: in vitro and in vivo characterization. J Immunol. 1978;121:1157–66. source
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, certain peptides such as substance P can activate some mast cell populations to robustly release the granule-stored mediators; however, compared to the same cells activated via the FcεRI, such stimuli may less potently elicit release of lipid mediators or cytokines [14, 20, 21].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Innate activation of mast cells.
What the sources say
- Not checked — no full text of the sourcecites [14] Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol. 2005;23:749–86. source
- Not checked — no full text of the sourcecites [20] Jensen BM, Frandsen PM, Raaby EM, Schiotz PO, Skov PS, Poulsen LK. Molecular and stimulus-response profiles illustrate heterogeneity between peripheral and cord blood-derived human mast cells. J Leukoc Biol. 2014;95:893–901. source
- Check pendingcites [21] McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519:237–41. source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Yukihiko Kitamura and colleagues discovered that (WB/Re-W/+ X C57BL/6-Wv/+)F1-”W/Wv” mice (now known as WBB6F1-KitW/KitW-v mice, since “W” later was shown to encode c-kit [54, 55]) not only had a moderate macrocytic anemia, a phenotype which had been reported decades earlier, but were profoundly deficient in tissue mast cells [56].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > “Mast cell knock-in mice”.
What the sources say
- Not checked — no full text of the sourcecites [54] Chabot B, Stephenson DA, Chapman VM, Besmer P, Bernstein A. The proto-oncogene c‑kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988;335:88–9. source
- Not checked — no full text of the sourcecites [55] Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c‑kit proto-oncogene. Cell. 1988;55:185–92. source
- Not checked — no full text of the sourcecites [56] Kitamura Y, Go S, Hatanaka K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood. 1978;52:447–52. source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Brown et al. found that treatment of tick-sensitized guinea pigs with rabbit ABS markedly diminished basophils in the bone marrow, blood, and skin at sites of tick feeding of the sensitized guinea pigs, and also resulted in diminished numbers of eosinophils at such feeding sites [45].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Evidence for a beneficial role of basophils in acquired immunity to the feeding of ixodid ticks.
What the sources say
- Not checked — no full text of the sourcecites [45] Brown SJ, Galli SJ, Gleich GJ, Askenase PW. Ablation of immunity to amblyomma americanum by anti-basophil serum: cooperation between basophils and eosinophils in expression of immunity to ectoparasites (ticks) in guinea pigs. J Immunol. 1982;129:790–6. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Nakano et al. showed that the transfer of WBB6F1-+/+ mouse bone marrow-derived cultured mast cells (BMCMCs) i.v., i.p. or i.d. into WBB6F1-W/Wv mice had no effect on the anemia of the recipient mice but resulted in the appearance of mast cells in their tissues, and that, over time, these mast cell populations came to exhibit certain phenotypic features similar to those present in the corresponding”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > “Mast cell knock-in mice”.
What the sources say
- Check pendingcites [63] Nakano T, Sonoda T, Hayashi C, Yamatodani A, Kanayama Y, Yamamura T, et al. Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells. J Exp Med. 1985;162:1025–43. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This work showed that mast cells could diminish the toxicity of VIP, helodermin, and the whole venom of H. suspectum, and that this was largely or wholly dependent on mast cell-derived mMCP4 rather than CPA3 [18].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Not checked yetcites [18] Akahoshi M, Song CH, Piliponsky AM, Metz M, Guzzetta A, Abrink M, et al. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice. J Clin Invest. 2011;121:4180–91. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Abnormalities in host responses to certain parasites have been observed in mice that genetically lack IgE [27, 28], mast cells [29–33], or basophils [28, 33] but such studies generally have not included an analysis of the effects of those deficiencies on the overall survival or reproductive success of the infected hosts.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Possible beneficial functions of mast cells, basophils and IgE.
What the sources say
- Not checked — no full text of the sourcecites [27] Spencer LA, Porte P, Zetoff C, Rajan TV. Mice genetically deficient in immunoglobulin E are more permissive hosts than wild-type mice to a primary, but not secondary, infection with the filarial nematode Brugia malayi. Infect Immun. 2003;71:2462–7. source
- Check pendingcites [28] Schwartz C, Turqueti-Neves A, Hartmann S, Yu P, Nimmerjahn F, Voehringer D. Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion. Proc Natl Acad Sci USA. 2014;111:E5169–77. source
- Not checked — no full text of the sourcecites [29] Nawa Y, Kiyota M, Korenaga M, Kotani M. Defective protective capacity of W/Wv mice against strongyloides ratti infection and its reconstitution with bone marrow cells. Parasite Immunol. 1985;7:429–38. source
- Check pendingcites [30] Knight PA, Wright SH, Lawrence CE, Paterson YY, Miller HR. Delayed expulsion of the nematode trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease‑1. J Exp Med. 2000;192:1849–56. source
- Check pendingcites [31] Furuta T, Kikuchi T, Iwakura Y, Watanabe N. Protective roles of mast cells and mast cell-derived TNF in murine malaria. J Immunol. 2006;177:3294–302. source
- Not checked — no full text of the sourcecites [32] Maurer M, Lopez Kostka S, Siebenhaar F, Moelle K, Metz M, Knop J, et al. Skin mast cells control T cell-dependent host defense in Leishmania major infections. FASEB J. 2006;20:2460–7. source
- Not checked — no full text of the sourcecites [33] Ohnmacht C, Voehringer D. Basophils protect against reinfection with hookworms independently of mast cells and memory Th2 cells. J Immunol. 2010;184:344–50. source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances.”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Abstract
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metz et al. showed that mast cells not only diminished the toxicity of sarafotoxin 6b and enhanced the survival of mice injected with that peptide, but also did so in mice injected with the whole venom of A. engaddensis [15].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Identifying a beneficial role for mast cells in enhancing innate resistance to venoms.
What the sources say
- Not checked — no full text of the sourcecites [15] Metz M, Piliponsky AM, Chen CC, Lammel V, Abrink M, Pejler G, et al. Mast cells can enhance resistance to snake and honeybee venoms. Science. 2006;313:526–30. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“When mast cell- or basophil-bound IgE antibodies recognize antigens that are at least bivalent, rapid aggregation of the FcεRI initiates complex intra-cellular signaling pathways. This ultimately results in the release, by such activated effector cells, of a wide variety of mediators with diverse biological effects [5, 6, 8–11].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Mast cells, basophils and IgE in the pathology of allergic disorders.
What the sources say
- Not checked — no full text of the sourcecites [5] Kinet JP. The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annu Rev Immunol. 1999;17:931–72. source
- Check pendingcites [6] Rivera J, Fierro NA, Olivera A, Suzuki R. New insights on mast cell activation via the high affinity receptor for IgE. Adv Immunol. 2008;98:85–120. source
- Not checked — no full text of the sourcecites [8] Karasuyama H, Mukai K, Obata K, Tsujimura Y, Wada T. Nonredundant roles of basophils in immunity. Annu Rev Immunol. 2011;29:45–69. source
- Check pendingcites [9] Sullivan BM, Liang HE, Bando JK, Wu D, Cheng LE, McKerrow JK, et al. Genetic analysis of basophil function in vivo. Nat Immunol. 2011;12:527–35. source
- Not checked — no full text of the sourcecites [10] Voehringer D. Protective and pathological roles of mast cells and basophils. Nat Rev Immunol. 2013;13:362–75. source
- Check pendingcites [11] Kawakami T, Kitaura J. Mast cell survival and activation by IgE in the absence of antigen: a consideration of the biologic mechanisms and relevance. J Immunol. 2005;175:4167–73. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In addition to using the original mast cell-deficient WBB6F1-KitW/KitW-v mice to prepare “mast cell knock-in mice”, this approach also can be employed using C57BL/6-KitW-sh/KitW-sh mice, which have the advantage of being inbred, fertile and not anemic [68, 69, 73].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > “Mast cell knock-in mice”.
What the sources say
- Check pendingcites [68] Grimbaldeston MA, Chen CC, Piliponsky AM, Tsai M, Tam SY, Galli SJ. Mast cell-deficient W‑sash c‑kit mutant KitW‑sh/W-sh mice as a model for investigating mast cell biology in vivo. Am J Pathol. 2005;167:835–48. source
- Check pendingcites [69] Wolters PJ, Mallen-St. Clair J, Lewis CC, Villalta SA, Baluk P, Erle DJ, et al. Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient KitW‑sh/KitW‑sh sash mice. Clin Exp Allergy. 2005;35:82–8. source
- Check pendingcites [73] Nigrovic PA, Gray DH, Jones T, Hallgren J, Kuo FC, Chaletzky B, et al. Genetic inversion in mast cell-deficient Wsh mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. Am J Pathol. 2008;173:1693–701. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Such tunicates also have been reported to have cells resembling basophils [111].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > Conclusions.
What the sources say
- Not checked — no full text of the sourcecites [111] de Barros CM, Andrade LR, Allodi S, Viskov C, Mourier PA, Cavalcante MC, et al. The Hemolymph of the ascidian styela plicata (chordata-tunicata) contains heparin inside basophil-like cells and a unique sulfated galactoglucan in the plasma. J Biol Chem. 2007;282:1615–26. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Independently of our work, Palm et al. showed that mice immunized with the major allergen contained in honeybee venom, bee venom phospholipase A2 (bvPLA2), exhibited enhanced resistance to the ability of bvPLA2 to induce hypothermia upon its injection into mice, and also provided evidence that this enhanced immunity required B cells and was diminished significantly in mice which lacked the IgE”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Check pendingcites [104] Palm NW, Rosenstein RK, Yu S, Schenten DD, Florsheim E, Medzhitov R. Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity. Immunity. 2013;39:976–85. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“DNP-specific IgG isotypes with the capacity to activate effector cells via Fcγ receptors [108]”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked — no full text of the sourcecites [108] Bruhns P. Properties of mouse and human IgG receptors and their contribution to disease models. Blood. 2012;119:5640–9. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The latter finding suggested that mast cells can contribute to IgE-mediated acquired resistance to honeybee venom, as well as enhance the innate resistance of mice to a first exposure to that venom [15].”
§ Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy[1] > IgE can contribute to host defense against arthropod and reptile venoms.
What the sources say
- Not checked — no full text of the sourcecites [15] Metz M, Piliponsky AM, Chen CC, Lammel V, Abrink M, Pejler G, et al. Mast cells can enhance resistance to snake and honeybee venoms. Science. 2006;313:526–30. source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Findings in mice about mast cells, IgE, and venom resistance are relevant to human allergy and venom defense.
“These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances.”
The paper relies on this without support.
The venoms used in mouse experiments are representative of animal venoms that threaten humans.
“our initial evidence indicated that mast cells can increase the innate resistance of mice upon their first exposure to the venoms of 3 species of poisonous snakes, the Gila monster, the honeybee, or two especially dangerous scorpions.”
The paper relies on this without support.
Vertebrates have been subjected to evolutionary pressure through millions of years of co-evolution with venomous arthropods, reptiles, and other species.
“However, in addition to parasites, vertebrates also have been subjected to evolutionary pressure through millions of years of co-evolution with venomous arthropods, reptiles, and other species.”
Citations
Cites
IgE and mast cells in allergic disease
Galli, S. J., & Tsai, M. (2012) · Nature Medicine · doi:10.1038/nm.2755 · Cited by 1,799
Self-citationCetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose
Chung, C. H., Mirakhur, B., Chan, E., Le, Q.-T., Berlin, J., Morse, M., Murphy, B. A., Satinover, S. M., Hosen, J., Mauro, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa074943 · Cited by 1,521
Bee and Wasp Venoms: The biochemistry and pharmacology of their peptides and enzymes are reviewed.
Habermann, E. (1972) · Science · doi:10.1126/science.177.4046.314 · Cited by 1,324
The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene
Geissler, E. N., Ryan, M. A., & Housman, D. E. (1988) · Cell · doi:10.1016/0092-8674(88)90020-7 · Cited by 1,287
Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions
McNeil, B. D., Pundir, P., Meeker, S., Han, L., Undem, B. J., Kulka, M., & Dong, X. (2015) · Nature · doi:10.1038/nature14022 · Cited by 1,228
Galli, S. J., Borregaard, N., & Wynn, T. A. (2011) · Nature Immunology · doi:10.1038/ni.2109 · Cited by 1,055
Self-citationMAST CELLS AS “TUNABLE” EFFECTOR AND IMMUNOREGULATORY CELLS: Recent Advances
Galli, S. J., Kalesnikoff, J., Grimbaldeston, M. A., Piliponsky, A. M., Williams, C. M. M., & Tsai, M. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141025 · Cited by 1,017
Self-citationHow are TH2-type immune responses initiated and amplified?
Paul, W. E., & Zhu, J. (2010) · Nature reviews. Immunology · doi:10.1038/nri2735 · Cited by 997
The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus
Chabot, B., Stephenson, D. A., Chapman, V. M., Besmer, P., & Bernstein, A. (1988) · Nature · doi:10.1038/335088a0 · Cited by 994
THE HIGH-AFFINITY I g E RECEPTOR (FcεRI): From Physiology to Pathology
Kinet, J.-P. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.931 · Cited by 968
Research works printed but not linked: 1
- Portier MM, Richet C. De l’action anaphylactique de certains venims. C R Seances Soc Biol Fil. 1902;54:170–2.
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Probiotics: mechanism of action, health benefits and their application in food industries
Latif, A., Shehzad, A., Niazi, S., Zahid, A., Ashraf, W., Iqbal, M. W., Rehman, A., Riaz, T., Aadil, R. M., Khan, I. M., et al. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1216674 · Cited by 749
Cellular and molecular mechanisms of allergic asthma
Komlósi, Z. I., van de Veen, W., Kovács, N., Szűcs, G., Sokołowska, M., O’Mahony, L., Akdiş, M., & Akdiş, C. A. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100995 · Cited by 271
Landscape of mast cell populations across organs in mice and humans
Tauber, M., Basso, L., Martin, J.-C., Bostan, L. E., Pinto, M. M., Thierry, G. R., Houmadi, R., Serhan, N., Loste, A., Blériot, C., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20230570 · Cited by 153
Self-citationAllergy, Anaphylaxis, and Nonallergic Hypersensitivity: IgE, Mast Cells, and Beyond
Vitte, J., Vibhushan, S., Bratti, M., Montero-Hernández, J. E., & Blank, U. (2022) · Medical Principles and Practice · doi:10.1159/000527481 · Cited by 110
Gutiérrez, J. M., Albulescu, L.-O., Clare, R. H., Casewell, N. R., El‐Aziz, T. M. A., Escalante, T., & Rucavado, A. (2021) · Toxins · doi:10.3390/toxins13070451 · Cited by 100
Metadata
- Authors
- Galli, S. J., Metz, M., Starkl, P., Marichal, T., & Tsai, M.
- Affiliations
- Stanford Medicine (US)
- Charité – Universitätsmedizin Berlin (DE)
- Austrian Academy of Sciences (AT)
- University of Liège (BE)
- Corresponding author
- Galli, Stephen J.
- Venue
- Allergo Journal International
- Published
- 2020-03
- Volume
- 29
- Issue
- 2
- Pages
- 46-62
- ISSN
- 2197-0378 (ISSN-L)
- PMC
- PMC7673288
- OpenAlex
- W3009230457
- Cited by
- 57
- References
- 116
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 1
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- Allergo Journal International (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ORBi (University of Liège) (submittedVersion)
- Funders
- National Cancer Institute (R01CA072074)
- National Institute of Allergy and Infectious Diseases (R01AI023990, R37AI023990, U19AI104209)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR067145)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Venomous Animal Envenomation and Studies
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Keywords
- mast cells, IgE, venom resistance, anaphylaxis, Th2 immune response, FcεRI, basophils, honey bee venom, Russell's viper venom, helminth immunity, tick immunity, adaptive immunity, innate immunity, allergy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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