Host Resistance Assays

  • Stefanie C. M. Burleson
  • Wendy Jo Freebern
  • Florence G. Burleson
  • Gary R. Burleson
  • Victor J. Johnson
  • Robert W. Luebke
Part of the Methods in Molecular Biology book series (MIMB, volume 1803)


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.

Key words

Host resistance Immunotoxicity Immunosuppression Susceptibility to infection Viral infections Latent viral infections Bacterial infections Parasite infections 



Animal biosafety level


Antibody-dependent cellular cytotoxicity


Biosafety level


Thymus-derived lymphocyte bearing the CD4 antigen


Thymus-derived lymphocyte bearing the CD8 antigen




Circumsporozoite protein


Cytotoxic T lymphocyte


Dendritic cell


Epstein-Barr virus


Enzyme-linked immunosorbent assay


International Council for Harmonisation (formerly the International Conference on Harmonisation)


Interferon gamma


Immunoglobulin A


Immunoglobulin E


Immunoglobulin G


Immunoglobulin M








Keyhole limpet hemocyanin




Monoclonal antibody


Murine cytomegalovirus


Madin-Darby canine kidney


Major histocompatibility class I


Mouse mammary tumor virus


Methicillin-resistant Staphylococcus aureus


Myeloid differentiation primary response gene 88

MZB cell

Marginal zone B cell


NK cell

Natural killer cell


Nonlethal strain of Py


P. berghei


P. chabaudi


Plaque forming units

pRBC cells

Parasitized red blood cells


P. yoelii


Lethal strain of Py


Red blood cell


Rapid expulsion


Rhesus rhadinovirus


Severe combined immunodeficiency disease


Signal transducer and activator of transcription 6


Simian virus 40


Splenic tyrosine kinase


Tributyltin oxide


T-cell-dependent antibody response


Transforming growth factor beta


T-helper 1 cell


T-helper 2 cell


T-cell-independent antibody response


Toll-like receptor


Tumor necrosis factor alpha


T. spiralis



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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Stefanie C. M. Burleson
    • 1
  • Wendy Jo Freebern
    • 2
  • Florence G. Burleson
    • 1
  • Gary R. Burleson
    • 1
  • Victor J. Johnson
    • 1
  • Robert W. Luebke
    • 3
    • 4
  1. 1.Burleson Research Technologies, Inc. (BRT)MorrisvilleUSA
  2. 2.Bristol-Myers Squibb Company, ImmunotoxicologyNew BrunswickUSA
  3. 3.United States Environmental Protection Agency, Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Laboratory, Office of Research and DevelopmentResearch Triangle ParkUSA
  4. 4.Burleson Research Technologies, Inc.MorrisvilleUSA

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