The role of T follicular helper cells in induction and affinity maturation of IgE in immune responses to venom
Final Report Abstract
Envenoming due to bites or stings of venomous animals (primarily snakes) accounts for more than 100,000 deaths annually. Moreover, envenoming perpetuates the cycle of poverty, most affecting the poor and depriving them of the ability to work due to chronic health damage. Approximately 2 million people suffer from envenoming annually. The antibodies generated by the immune system play a crucial role in defense against venom. Antibodies can directly neutralize toxins contained in venom and furthermore, they can lead to cell-mediated neutralization of the toxins. Thus, antibody-mediated protection against venom is crucial in enhancing survival and improving outcomes after envenomation. On the other hand, antibodies against venom might elicit in some people anaphylaxis – a severe allergic reaction that could be more life-threatening than the envenoming itself. In fact, bee and wasp venom is (after food and drugs) one of the main elicitors of anaphylaxis. Thus, antibodies to venom are characterized by both protective and harmful effects, and they are a highly relevant research topic from a clinical point of view. T follicular helper (Tfh) cells were identified as cells supporting the generation of high-affinity antibodies. These cells were shown to be crucial help providers in immune responses induced by vaccines and aeroallergens, but not by some types of infections. The role of Tfh cells in immune responses induced by venom, the course of these responses, and the affinity of generated antibodies have never been previously examined in vivo and were the project’s subject. During this study, we were able to characterize the antibodies, antibody-producing cells, and Tfh cells induced by venom. We found that the help provided by Tfh cells is crucial for the generation of high-affinity antibodies after exposure to venom. Further, we investigated the role of IL-4, a factor produced by Tfh cells, in supporting the antibody induction by venom. The data gained during this project helps us to better understand immune reactions to venom. During the past decades, researchers have made significant progress in developing vaccines and therapies optimized against various pathogens by examining the mechanisms of immune responses to them. Similarly, our results characterizing the mechanism of induction of highaffinity antibodies by venom can contribute to the development of improved immunotherapy schemata for venom allergy, better antivenoms, and, most importantly, vaccines protecting against envenoming.
Publications
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Autumn Immunology Conference; 22-25 November 2023; Chicago, Humoral immune responses induced by venom are Tfh cell-dependent. Abstract, poster, and oral presentation.
Kraft, Magdalena
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Food Allergy Gordon Research Conference; 13-18 November 2023; Oxnard, California. Venom Allergy: Development of a Mouse Model. Abstract and poster.
Kraft, Magdalena
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Food Allergy Science Initiative (FASI) Annual Scientific Retreat;19 May 2023; Boston Humoral immune response to venom: differences in IgE and IgG1 kinetics. Abstract and poster.
Kraft, Magdalena
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Recent insights into the mechanisms of anaphylaxis. Current Opinion in Immunology, 81, 102288.
Stevens, Whitney W.; Kraft, Magdalena & Eisenbarth, Stephanie C.
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AAAAI Congress (Discovery); 23-26 February 2024; The role of Tfh cells in the humoral immune responses induced by venom. Abstract and poster.
Kraft, Magdalena
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Food Allergy Gordon Research Conference and Seminar; 6-12 January 2024; Ventura, California. Humoral immune responses induced by venom are Tfh celldependent. Abstract, poster, and oral presentation.
Kraft, Magdalena
