Abstract
The goal of immunotoxicity testing is to obtain data useful for immunotoxicity safety assessment. Guidance in the performance of immunotoxicity safety evaluations is provided in documents from the US EPA for chemicals and the ICH S8 document for pharmaceuticals. The ICH S8 document outlines a tiered approach that includes (1) standard toxicity studies with associated hematology, immune system organ weights, and histopathology data; (2) functional assays, such as cytotoxic T lymphocyte (CTL) assays, natural killer (NK) cell assays, respiratory burst, phagocytosis, and T-cell-dependent antibody response (TDAR) assays; and (3) host resistance assays. Host resistance assays are considered the gold standard in immunotoxicity testing and provide a critical overview of the extent to which innate, adaptive, and homeostatic regulatory immune functions are integrated to protect the host. Both comprehensive and targeted host resistance assays are available, each with distinct advantages. This chapter serves to provide a general overview of the various assays that may be used, as well as a summary of procedures.
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Abbreviations
- ABSL:
-
Animal biosafety level
- ADCC:
-
Antibody-dependent cellular cytotoxicity
- BSL:
-
Biosafety level
- CD4+ :
-
Thymus-derived lymphocyte bearing the CD4 antigen
- CD8+ :
-
Thymus-derived lymphocyte bearing the CD8 antigen
- CMV:
-
Cytomegalovirus
- CSP:
-
Circumsporozoite protein
- CTL:
-
Cytotoxic T lymphocyte
- DC:
-
Dendritic cell
- EBV:
-
Epstein-Barr virus
- ELISA:
-
Enzyme-linked immunosorbent assay
- ICH:
-
International Council for Harmonisation (formerly the International Conference on Harmonisation)
- IFNγ:
-
Interferon gamma
- IgA:
-
Immunoglobulin A
- IgE:
-
Immunoglobulin E
- IgG:
-
Immunoglobulin G
- IgM:
-
Immunoglobulin M
- IL-1:
-
Interleukin-1
- IL-10:
-
Interleukin-10
- IL-4:
-
Interleukin-4
- KLH:
-
Keyhole limpet hemocyanin
- LCV:
-
Lymphocryptovirus
- mAb:
-
Monoclonal antibody
- MCMV:
-
Murine cytomegalovirus
- MDCK:
-
Madin-Darby canine kidney
- MHC I:
-
Major histocompatibility class I
- MMTV:
-
Mouse mammary tumor virus
- MRSA:
-
Methicillin-resistant Staphylococcus aureus
- MyD88:
-
Myeloid differentiation primary response gene 88
- MZB cell:
-
Marginal zone B cell
- MΦ:
-
Macrophage
- NK cell:
-
Natural killer cell
- Py17XL:
-
Nonlethal strain of Py
- Pb:
-
P. berghei
- Pc:
-
P. chabaudi
- PFU:
-
Plaque forming units
- pRBC cells:
-
Parasitized red blood cells
- Py:
-
P. yoelii
- Py17XL:
-
Lethal strain of Py
- RBC:
-
Red blood cell
- RE:
-
Rapid expulsion
- RRV:
-
Rhesus rhadinovirus
- SCID:
-
Severe combined immunodeficiency disease
- STAT6:
-
Signal transducer and activator of transcription 6
- SV40:
-
Simian virus 40
- Syk:
-
Splenic tyrosine kinase
- TBTO:
-
Tributyltin oxide
- TDAR:
-
T-cell-dependent antibody response
- TGFβ:
-
Transforming growth factor beta
- Th1:
-
T-helper 1 cell
- Th2:
-
T-helper 2 cell
- TIAR:
-
T-cell-independent antibody response
- TLR:
-
Toll-like receptor
- TNFα:
-
Tumor necrosis factor alpha
- Ts:
-
T. spiralis
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Burleson, S.C.M., Freebern, W.J., Burleson, F.G., Burleson, G.R., Johnson, V.J., Luebke, R.W. (2018). Host Resistance Assays. In: DeWitt, J., Rockwell, C., Bowman, C. (eds) Immunotoxicity Testing. Methods in Molecular Biology, vol 1803. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8549-4_9
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