What Determines the Class of Immunity an Antigen Induces? A Foundational Question Whose Rational Consideration Has Been Undermined by the Information Overload
Activated CD4 T helper cells are required to activate B cells to produce antibody and CD8 T cells to generate cytotoxic T lymphocytes. In the absence of such help, antigens inactivate B cells and CD8 T cells. Thus, the activation or inactivation of CD4 T cells determines whether immune responses are...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/9/1253 |
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| author | Peter Bretscher |
| author_facet | Peter Bretscher |
| author_sort | Peter Bretscher |
| collection | DOAJ |
| description | Activated CD4 T helper cells are required to activate B cells to produce antibody and CD8 T cells to generate cytotoxic T lymphocytes. In the absence of such help, antigens inactivate B cells and CD8 T cells. Thus, the activation or inactivation of CD4 T cells determines whether immune responses are generated, or potentially ablated. Most consider that the activation of CD4 T cells requires an antigen-dependent signal, signal 1, as well as a critical costimulatory signal, initiated when a pattern recognition receptor (PRR) engages with a danger- or pathogen-associated molecular pattern (DAMP or PAMP). Most also envisage that the nature of the DAMP/PAMP signal determines the Th subset predominantly generated and so the class of immunity predominantly induced. I argue that this framework is implausible as it is incompatible with diverse observations of the variables of immunization affecting the class of immunity induced. An alternative framework, the threshold hypothesis, posits that different levels of antigen mediated CD4 T cell interactions lead to the generation of different Th subsets and so different classes of immunity, that it is compatible with these observations. This alternative supports a rational approach to preventing and treating diverse clinical conditions associated with infectious disease and, more speculatively, with cancer. |
| first_indexed | 2024-03-10T23:01:55Z |
| format | Article |
| id | doaj.art-e128de4b150249d29aff478fc4485cff |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T23:01:55Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-e128de4b150249d29aff478fc4485cff2023-11-19T09:39:09ZengMDPI AGBiology2079-77372023-09-01129125310.3390/biology12091253What Determines the Class of Immunity an Antigen Induces? A Foundational Question Whose Rational Consideration Has Been Undermined by the Information OverloadPeter Bretscher0Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaActivated CD4 T helper cells are required to activate B cells to produce antibody and CD8 T cells to generate cytotoxic T lymphocytes. In the absence of such help, antigens inactivate B cells and CD8 T cells. Thus, the activation or inactivation of CD4 T cells determines whether immune responses are generated, or potentially ablated. Most consider that the activation of CD4 T cells requires an antigen-dependent signal, signal 1, as well as a critical costimulatory signal, initiated when a pattern recognition receptor (PRR) engages with a danger- or pathogen-associated molecular pattern (DAMP or PAMP). Most also envisage that the nature of the DAMP/PAMP signal determines the Th subset predominantly generated and so the class of immunity predominantly induced. I argue that this framework is implausible as it is incompatible with diverse observations of the variables of immunization affecting the class of immunity induced. An alternative framework, the threshold hypothesis, posits that different levels of antigen mediated CD4 T cell interactions lead to the generation of different Th subsets and so different classes of immunity, that it is compatible with these observations. This alternative supports a rational approach to preventing and treating diverse clinical conditions associated with infectious disease and, more speculatively, with cancer.https://www.mdpi.com/2079-7737/12/9/1253immune class regulationhumoral immunitycell-mediated immunityantigen doseefficacy of immunity |
| spellingShingle | Peter Bretscher What Determines the Class of Immunity an Antigen Induces? A Foundational Question Whose Rational Consideration Has Been Undermined by the Information Overload Biology immune class regulation humoral immunity cell-mediated immunity antigen dose efficacy of immunity |
| title | What Determines the Class of Immunity an Antigen Induces? A Foundational Question Whose Rational Consideration Has Been Undermined by the Information Overload |
| title_full | What Determines the Class of Immunity an Antigen Induces? A Foundational Question Whose Rational Consideration Has Been Undermined by the Information Overload |
| title_fullStr | What Determines the Class of Immunity an Antigen Induces? A Foundational Question Whose Rational Consideration Has Been Undermined by the Information Overload |
| title_full_unstemmed | What Determines the Class of Immunity an Antigen Induces? A Foundational Question Whose Rational Consideration Has Been Undermined by the Information Overload |
| title_short | What Determines the Class of Immunity an Antigen Induces? A Foundational Question Whose Rational Consideration Has Been Undermined by the Information Overload |
| title_sort | what determines the class of immunity an antigen induces a foundational question whose rational consideration has been undermined by the information overload |
| topic | immune class regulation humoral immunity cell-mediated immunity antigen dose efficacy of immunity |
| url | https://www.mdpi.com/2079-7737/12/9/1253 |
| work_keys_str_mv | AT peterbretscher whatdeterminestheclassofimmunityanantigeninducesafoundationalquestionwhoserationalconsiderationhasbeenunderminedbytheinformationoverload |