Species differences in the structure and function of the immune system
Abstract
With the recent publication of regulatory guidelines from both the FDA and the CPMP addressing the investigation of immunotoxicity of new chemical entities has come the requisite increased application of immunotoxicology protocols. Importantly, the fulfillment of these protocols may require the use of different species, and while in many cases information concerning the structure and function of the immune system can be readily translated across species, there are numerous and significant species differences that need to be considered. In some cases, the generation of meaningful immunotoxicology data can be adversely affected by the choice of a species that does not adequately share the immune function of concern with man. Likewise immunotoxicology testing in one species may produce negative data in one species but positive data in another. Knowing the mechanistic basis through an understanding of species differences in the structure and function of the immune system is pivotal to success. This becomes especially true as pharmaceutical companies design and develop highly specific immunomodulatory molecules that demonstrate species-specific pharmacology. This review is an exploration of various species differences in the structure and function of the immune system and an attempt to identify those differences that may be important in the conduct of immunotoxicity tests.
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Inconsistencies in the literature may stem from the use of cell lines or murine primary cells, which do not fully represent primary human monocyte-derived macrophages.
“These inconsistencies may stem from the use of cell lines or murine primary cells, which do not fully represent the behaviour of primary human monocyte-derived macrophages.”
From Soft tissue-mimicking hydrogel stiffness modulates polarisation of human monocyte-derived macrophages (2025) · cites this paper as [27]
Most works on stiffness and macrophages have predominantly relied on cell lines or murine primary cells, with limited investigation using primary human monocyte-derived macrophages.
“Additionally, most works have predominantly relied on cell lines or murine primary cells, with limited investigation using primary human monocyte-derived macrophages.”
From Soft tissue-mimicking hydrogel stiffness modulates polarisation of human monocyte-derived macrophages (2025) · cites this paper as [27]
The general structure of the immune system in mice and humans is very similar, though discrepancies in both the innate and adaptive immune system exist.
“The general structure of the immune system in mice and humans is also very similar, though discrepancies in both the innate and adaptive immune system exist”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Haley, 2003
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References 174 · Cited by 336
- Authors
- Haley, P. J.
- Affiliations
- AstraZeneca (United States) (US)
- Corresponding author
- Haley, Patrick J.
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 2003-06
- Volume
- 188
- Issue
- 1
- Pages
- 49-71
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W2026529532
- Cited by
- 336
- References
- 174
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 20 · 2023: 13 · 2022: 11 · 2021: 12 · 2020: 16 · 2019: 25 · 2018: 25 · 2017: 21 · 2016: 19 · 2015: 21 · 2014: 18 · 2013: 17 · 2012: 12
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- species differences, immunotoxicity testing, interspecies extrapolation, immunomodulators, new chemical entities
- MeSH terms
- Animals, Animals, Laboratory, Immunotoxins, Drug Evaluation, Preclinical, Humans, Immune System, Species Specificity, United States, United States Food and Drug Administration, Risk Assessment, Toxicity Tests
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