REVIEW SUMMARY
◥IMMUNOLOGY
The science and medicine of human immunology
Bali Pulendran*and Mark M. Davis
BACKGROUND:The mammalian immune sys-
tem is a remarkable sensory system for the
detection and neutralization of pathogens.
History is replete with the devastating effects
of plagues, and the coronavirus disease 2019
(COVID-19) pandemic is a defining global
health crisis of our time. Although the devel-
opment of effective vaccines has saved many
lives, the basic workings of the immune system
are complex and require the development of
animal models, such as inbred mice. Indeed,
research in mice has been enormously pro-
ductive, and the tremendous insights gleaned
have resulted in many Nobel prizes and other
accolades. However, past results are not nec-
essarily a reliable guide to the future, and a
notable limitation of animal models has been
their failure to accurately model some hu-
man diseases and their inability to predict
human immune responses in many cases.
With regard to inbred mice, which have been
the principal model of choice for immunol-
ogy, this is likely due to the compromises
that were necessary to create a more tracta-
ble and reproducible system for experimen-
tation, such as genetic uniformity and lack of
pathogen exposure, as well as the fact that
mice are evolutionarily quite distinct. These
considerations suggest that direct studies of
the human immune system are likely to be
extremely rewarding, both from a scientific
and a medical perspective.ADVANCES:In the past decade there has been
an explosion of new approaches and technol-
ogies to explore the human immune system
with unprecedented precision. Insights into
the human immune response to vaccination,
cancers, and viral infections such as COVID-19
have come from high-throughput“omics”tech-
nologies that measure the behavior of genes,
mRNA (single-cell transcriptomics), proteins
(proteomics), metabolites (metabolomics), cells
(mass cytometry), and epigenetic modifica-tions (ATAC-seq), coupled with computational
approaches.OUTLOOK:Sydney Brenner remarked in 2008,
“We don’t have to look for a model organism
anymore.Becausewearethemodelorgan-
isms.”We propose that studying the immune
system in humans, who are genetically diverse
and afflicted by a multitude of diseases, offers
both a direct link to medicine (i.e.,“transla-
tion”) and the very real prospect of discovering
fundamentally new human biology. New ap-
proaches and technology are now making this
area much more approachable, but profiling
immunity in humans is but the first step. Com-
putational mining of the data and biological
validation in animal models or human organ-
oids are essential next steps, in an iterative cycle
that seeks to bridge fundamental and applied
science, as well as mouse and human immu-
nology, in a seamless continuum of scientific
discovery and translational medicine. This will
represent a new paradigm for accelerating the
development of vaccines and therapeutics.▪RESEARCH
1582 25 SEPTEMBER 2020•VOL 369 ISSUE 6511 sciencemag.org SCIENCE
The list of author affiliations is available in the full article online.
*Corresponding author. Email: [email protected]
Cite this article as B. Pulendran, M. M. Davis,Science 369 ,
eaay4014 (2020). DOI: 10.1126/science.aay4014READ THE FULL ARTICLE AT
https://doi.org/10.1126/science.aay4014Probing the human immune response to viral infections.Systems biology techniques can be used to probe the human immune response to viral infections and
can define molecular signatures that predict disease severity and illuminate the underlying mechanisms of disease. ILLUSTRATION: KELLIE HOLOSKI/
SCIENCE