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Host Resistance Assays

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Immunotoxicity Testing

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1803))

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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This report has been reviewed by the Environmental Protection Agency’s Office of Research and Development and approved for publication. Approval does not signify that the contents reflect the views of the Agency.

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Authors and Affiliations

  1. Burleson Research Technologies, Inc. (BRT), Morrisville, NC, USA

    Stefanie C. M. Burleson, Florence G. Burleson, Gary R. Burleson & Victor J. Johnson

  2. Bristol-Myers Squibb Company, Immunotoxicology, New Brunswick, NJ, USA

    Wendy Jo Freebern

  3. United States Environmental Protection Agency, Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Laboratory, Office of Research and Development, Research Triangle Park, NC, USA

    Robert W. Luebke

  4. Burleson Research Technologies, Inc., Morrisville, NC, USA

    Robert W. Luebke

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  1. Stefanie C. M. Burleson
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  4. Gary R. Burleson
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology, East Carolina University, Greenville, North Carolina, USA

    Jamie C. DeWitt

  2. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA

    Cheryl E. Rockwell

  3. Durham, North Carolina, USA

    Christal C. Bowman

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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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  • DOI: https://doi.org/10.1007/978-1-4939-8549-4_9

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