American Association of Immunologists Recommendations for an Undergraduate Course in Immunology

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American Association of Immunologists Recommendations for
an Undergraduate Course in Immunology
Edith Porter, Eyal Amiel, Nandita Bose, Andrea Bottaro, William H. Carr, Michelle
Swanson-Mungerson, Steven M. Varga and Julie M. Jameson

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ImmunoHorizons 2021, 5 (6) 448-465
doi: https://doi.org/10.4049/immunohorizons.2100030
http://www.immunohorizons.org/content/5/6/448
This information is current as of March 14, 2022.

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ISSN 2573-7732.
ON THE HORIZON

American Association of Immunologists Recommendations for
an Undergraduate Course in Immunology
Edith Porter,* Eyal Amiel,† Nandita Bose,‡ Andrea Bottaro,§ William H. Carr,{ Michelle Swanson-Mungerson,k
Steven M. Varga,#,**,†† and Julie M. Jameson‡‡
*Department of Biological Sciences, California State University Los Angeles, Los Angeles, CA; †Department of Biomedical and Health
Sciences, University of Vermont, Burlington, VT; ‡HiberCell, Inc., Roseville, MN; §Department of Biomedical Sciences, Cooper Medical School

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of Rowan University, Camden, NJ; {Department of Biology, Medgar Evers College, City University of New York, Brooklyn, NY; kDepartment
of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL; #Department of
Microbiology and Immunology, University of Iowa, Iowa City, IA; **Interdisciplinary Graduate Program in Immunology, University of Iowa,
Iowa City, IA; ††Department of Pathology, University of Iowa, Iowa City, IA; and ‡‡Department of Biological Sciences, California State
University San Marcos, San Marcos, CA

ABSTRACT
Identifying the “essential” components of an undergraduate immunology lecture course can be daunting because of the varying
postgraduate pathways students take. The American Association of Immunologists Education Committee commissioned an Ad Hoc
Committee, representing undergraduate, graduate, and medical institutions as well as the biotechnology community, to develop core
curricular recommendations for teaching immunology to undergraduates. In a reiterative process involving the American Association of
Immunologists teaching community, 14 key topics were identified and expanded to include foundational concepts, subtopics and
examples, and advanced subtopics, providing a flexible list for curriculum development and avenues for higher-level learning.
Recommendations for inclusive and antiracist teaching that outline opportunities to meet the needs of diverse student populations were
also developed. The consensus recommendations can be used to accommodate various course settings and will bridge undergraduate
and graduate teaching and prepare diverse students for subsequent careers in the biomedical field. ImmunoHorizons, 2021, 5: 448–465.

INTRODUCTION                                                                           recognition of the critical need for enhanced guidance on
                                                                                       undergraduate immunology curricular development, several
Immunology is challenging to teach in the undergraduate set-                           recent publications have begun the process of advocacy around
ting because of its rapidly advancing and expanding field of                           a more-unified approach to undergraduate immunology educa-
knowledge. The task of defining the key components of an                               tion (3, 4). Of note, a recent study that reported the results of
undergraduate curriculum in immunology can be overwhelm-                               surveyed immunology educators has helped identify current
ing to undergraduate educators, who are often challenged to                            curricular practices by experienced instructors, which has
cover the “essential” components of this vast field of science                         highlighted curricular priorities for both course and curriculum
through a combination of smaller units in general biology                              design for the field (5). All of these efforts are rooted in the
courses or within a single semester-long introductory course (1,                       premise that broader attention to a cohesive set of key concepts
2). Few resources are available that use a methodical approach                         and evidence-based curriculum design leads to improved stu-
to capture the key topics for inclusion in the course. In                              dent understanding and outcomes (5, 6). Professional scientific

Received for publication March 25, 2021. Accepted for publication April 22, 2021.
Address correspondence and reprint requests to: Prof. Edith Porter, California State University Los Angeles, BS 143, 5151 State University Drive, Los Angeles,
CA 90032. E-mail address: eporter@calstatela.edu
ORCIDs: 0000-0002-4656-5264 (E.P.); 0000-0002-1578-8705 (E.A.); 0000-0003-1712-6796 (A.B.); 0000-0003-1987-9070 (W.H.C.); 0000-0001-6384-6933
(M.S.-M.); 0000-0001-7332-4290 (S.M.V.); 0000-0003-0727-4066 (J.M.J.).
Abbreviations used in this article: AAI, American Association of Immunologists; ITIG, Immunology Teaching Interest Group.
This article is distributed under the terms of the CC BY-NC-ND 4.0 Unported license.
Copyright © 2021 The Authors

448                                                                                                             https://doi.org/10.4049/immunohorizons.2100030

ImmunoHorizons is published by The American Association of Immunologists, Inc.
ImmunoHorizons                                                                                                                 449

                                                                       (i.e., medical schools, graduate schools) or in the future work
                                                                       environment (i.e., biotechnology and pharmaceutical sectors)
                                   AHC                                 should have a seat at the table for decisions on key topics to
                                 Key topics                            make the undergraduate curriculum relevant. This reverse
                                                                       engineering strategy will provide the knowledge needed in the
                            ITIG                                       undergraduate curriculum to succeed at these higher levels. To
                         Survey and                                    meet these goals, the AAI Education Committee has embarked
                          working                                      on a mission to gain broad community consensus on an under-
                           groups                                      graduate immunology curriculum that bridges undergraduate
                                                                       education and postgraduate education/career-relevant needs.
                                   AHC                                      Starting in 2016, the AAI Education Committee initiated a
                                Refinement                             new annual meeting session focused on improving immunology
                                                                       education: the Immunology Teaching Interest Group (ITIG).
                                                                       This Education Committee--sponsored session has been dedi-
                            ITIG
                                                                       cated to sharing novel teaching practices for immunology edu-
                         Survey and

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                                                                       cation at undergraduate, graduate, and medical schools. ITIG
                          workshop
                                                                       speakers and attendees have included immunology educators
                                                                       spanning a range of institution types and serving students of
                                   AHC                                 different levels. The ITIG session has become a venue for the
                                Finalization                           exchange of ideas and a way to provide suggestions to the AAI
                                                                       community as a whole. The group has grown from 20 partici-
                                                                       pants in 2016 to more than 200 in 2020. Novel ideas and cut-
                           AAI EC
                                                                       ting-edge teaching strategies have been shared at the AAI
                                                                       Annual Meeting and in a special section of the AAI Newsletter
                           Review
                                                                       that is dedicated to pedagogy. The rising interest in immunol-
                                                                       ogy education is also reflected in recently published articles,
                                                                       which have begun to highlight effective teaching pedagogies
                                AAI Council                            and topics to cover (4, 9, 10).
                                                                            The AAI Education Committee received input from the
                                                                       ITIG highlighting a need for a comprehensive set of cur-
                           Broader                                     ricular guidelines for teaching immunology at the under-
                        dissemination                                  graduate level. In 2019, the Education Committee formed
                                                                       an Ad Hoc Committee to establish recommendations for
                                                                       undergraduate immunology instruction with the goal of
                                                                       providing a guide for instructors in immunology that will
FIGURE 1. Process of reiterative curriculum recommendation             bridge undergraduate and graduate teaching and prepare
development.                                                           students for subsequent careers in the biomedical and
AHC: American Association of Immunologists Curriculum Ad Hoc Commit-   healthcare fields as well as other areas applicable to immu-
tee, eight members; ITIG: 200 members; working groups, 47 members;    nology. The Ad Hoc Committee was composed of educa-
workshop, 49 participants. AAI EC, AAI Education Committee.            tors from primarily undergraduate academic institutions,
                                                                       educators in various healthcare sectors, and a member of
                                                                       the biotechnology community. The recommendations were
societies are uniquely poised to engage in broad curricular rec-       initially developed through consultation among the sub-
ommendations for their field based on the breadth of their             committee members and then thoroughly vetted by ITIG
membership expertise and the depth of their communication              members through a series of survey iterations, individual
platform to reach a broad section of researchers, educators, and       consultation, and a virtual workshop. The strength of these
professionals in the field (7, 8). In response to the perceived        recommendations lies in the vetting and broad consensus
need among immunology educators, the American Association              achieved by engaging over 70 immunologists in a variety of
of Immunologists (AAI) has undertaken a process to provide a           professional roles and the flexible structure to allow for
general set of core recommendations for an undergraduate cur-          innovations and autonomy of topic emphasis within the
riculum in the field of immunology. Ideally, curriculum guide-         curriculum.
lines would be developed with a top-down strategy identifying               In this article, we first describe the methodology used for
key topics that could be covered in shorter course modules and         curriculum content development, which may be useful for other
expanded subtopics that could be included in full-semester             disciplines aiming to develop curriculum recommendations for
courses. Additionally, educators at the next level of learning         complex, interdisciplinary subjects. Then we present the

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TABLE I. Key topics and their foundational concepts for an undergraduate course in immunology
       Key Topic                                 Foundational Concepts

       Overview and terminology of the           1.    Barrier function of epithelial tissues
       immune system                             2.    Immune system organs
                                                 3.    Hematopoiesis: myeloid and lymphoid lineage
                                                 4.    Cell types in myeloid and lymphoid lineages
                                                 5.    Primary and secondary lymphoid organs
                                                 6.    Complement
                                                 7.    Cytokines
                                                 8.    Antigen receptors of T cells
                                                 9.    Antigen receptors of B cells
                                                 10. Evolution of the immune system
       Immunological techniques                  1.    Animal models
                                                 2.    Cellular techniques considerations
                                                 3.    Antibodies for research, diagnostics, and therapeutics
                                                 4.    Flow cytometry
       Innate immunity                           1.    Functions of barriers and pre-formed elements
                                                 2.    Innate immune cell types and functions
                                                 3.    Differences of innate immunity from adaptive immunity
                                                 4.    Germline-encoded pattern recognition receptors
                                                 5.    Dendritic cells (DCs)

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       Inflammation                              1.    Principles of inflammation
                                                 2.    Hallmarks of inflammation
                                                 3.    Inflammatory inducers
                                                 4.    Intracellular response
                                                 5.    Inflammatory mediators
                                                 6.    Local response
                                                 7.    Systemic response
                                                 8.    Down regulators of inflammation
                                                 9.    Anti-inflammatory drugs
       Development & activation of self-         1.    Antigen receptor structure and mechanisms of diversity
       tolerant adaptive immune cells            2.    MHC and antigen presentation to T lymphocytes
                                                 3.    Generation and development of B and T lymphocytes
                                                 4.    Central tolerance mechanisms
                                                 5.    Lymphocyte activation and signal transduction- three signals concept
                                                 6.    Peripheral tolerance mechanisms
       Adaptive immune cell effector function    1.    Role of dendritic cells in activating naïve T cells
                                                 2.    Effector CD4 and CD8 T cells
                                                 3.    Antibody response
                                                 4.    Effector function of antibodies
                                                 5.    Adaptive immune response over time
       Integrated immune response                1.    Temporal immune response
                                                 2.    Spatial immune response
                                                 3.    Leukocyte trafficking
                                                 4.    Sequential activation of immune cells
                                                 5.    Leukocyte cross talk
                                                 6.    Immune response to pathogens
       Mucosal immunity                          1.    Organization of the mucosal immune system
                                                 2.    Specialized lymphoid cells located at mucosal sites
                                                 3.    Unique APC populations and uptake of antigen at mucosal sites
                                                 4.    Role of IgA in protection at mucosal sites
                                                 5.    Induction and regulation of the immune response at mucosal sites
       Active and passive immunizations          1.    Historical aspects of immunization
                                                 2.    Why vaccines work and concept of herd immunity
                                                 3.    Types of vaccines
                                                 4.    Important aspects of vaccines
                                                 5.    Vaccine production, adjuvants, and preservatives
                                                 6.    Challenges of vaccine success
                                                 7.    Passive immunization
       Tumor immunology                          1.    Tumor immunosurveillance
                                                 2.    Immune escape by tumors
                                                 3.    Cancer immunotherapy
       Allergies and Hypersensitivities          1.    Immunological hypersensitivities, definition and classification
                                                 2.    Main allergic reaction types according to the Gell-Coombs classification
                                                 3.    Principles of therapy of allergic reactions
       Autoimmune diseases                       1.    Causes, epidemiology, genetics
                                                 2.    Mechanisms of autoimmune disease
                                                 3.    Principles of therapy of autoimmune disease
       Transplant rejection                      1.    Transplant immunology
                                                 2.    Principles of immunosuppressive therapy for transplant rejection
       Immunodeficiencies                        1.    Primary immunodeficiencies
                                                 2.    Secondary immunodeficiencies
                                                 3.    Immunodeficiencies and immune dysregulation
                                                 4.    Diagnostic assessments used for both primary and secondary immunodeficiencies
                                                 5.    Treatments for immunodeficiencies
      Subtopics are numbered and examples are indicated by round bullets (●). Advanced subtopics are indicated by square bullets (■).

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TABLE II. Overview and terminology of the immune system
    Foundational Concepts                    Subtopics and Examples                                                                           Advanced Subtopics

    Barrier function of epithelial tissue    1.    Structural features of barrier defense
                                                   •      Keratinization
                                                   •      Mucous production
                                                   •      Ciliated epithelium
                                             2.    Chemical defenses
                                                   •      pH
                                             3.    Antimicrobial peptides and polypeptides and enzymes
                                                   •      Defensins
                                                   •      Cathelicidins
                                                   •      Lysozyme
                                             4.    Mucus, sweat, surfactants
                                             5.    Colonization of barrier surface by microbiome
    Immune system organs                     1.    Bone marrow
                                             2.    Primary lymphoid organs
                                             3.    Secondary lymphoid organs
                                             4.    Tertiary lymphoid structure
    Hematopoiesis: myeloid and               1.    Hematopoietic stem cell differentiation into specific lineage progenitors (common
    lymphoid lineage                               myeloid and common lymphoid progenitors, CMP and CLP)
                                             2.    Roles of cytokines and growth factors in hematopoiesis

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                                             3.    General functions associated with CMP and CLP progenitors
                                             4.    Modulation of hematopoiesis by environmental triggers (e.g. infection)
    Cell types in myeloid and lymphoid       1.    CMP Lineage
    lineages                                       •      Granulocytes (neutrophils, eosinophils, mast cells, basophils)
                                                   •      Monocytes, cacrophages
                                                   •      Dendritic cells
                                                   •      Erythrocytes
                                                   •      Megakaryocytes
                                             2.    CLP Lineage
                                                   •      B lymphocytes
                                                   •      Classical T lymphocytes (CD4 and CD8)
                                                   •      Non-classical lymphocytes (γ/δ, iNKT)
                                                   •      Innate Lymphocytes (NK cells, ILCs)
                                                   •      pDCs
    Primary and secondary lymphoid           1.    Defining role of bone marrow versus lymph nodes versus spleen in development of
    organs                                         immune cells and activation of immune responses
                                             2.    Functional distinction between primary and secondary lymphoid organs and lymphocyte
                                                   circulation
                                             3.    Spleen lymph node architecture and generalized function
                                             4.    Introduction of tissue-specific secondary lymphoid organs (e.g. BALT, GALT)
                                             5.    Lymphatics and lymph
    Complement                               1.    Major functions of complement
                                                   •      Opsonization
                                                   •      Anaphylatoxin-induced inflammation
                                                   •      Membrane attack complex
    Cytokines                                1.    Cytokine definition
                                                   •      Soluble protein messengers that specify and coordinate immunological activity
                                             2.    Chemokine definition
                                                   •      Mediators of cellular migration/recruitment
                                             3.    Cytokines families
                                             4.    Mechanism of cytokine receptor -dependent responses
                                                   •      Generic JAK/STAT signaling
    Antigen receptors of T cells             1.    Overview of TCR Structure
                                                   •      Alpha/beta chains
                                             2.    T cell receptor ligand (peptide/MHC)
                                             3.    Classes of MHC and antigen presentation
                                                   •      MHC I
                                                   •      MHC II
                                             4.    Major T cell subsets
                                                   •      CD8
                                                   •      CD4
    Antigen receptors of B cells             1.    Overview of antibody structure                                                            Description of diversity of
                                                   •      Heavy chains, light chains                                                          antibody structure across
                                                   •      Shape                                                                               vertebrate species
                                             2.    B cell receptor ligand (antigens)                                                          (camelids, sharks, etc.)
                                             3.    Functional domains of antibodies
                                                   •      Fab region, Fc region, hinge region
                                             4.    Overview of antibody functional properties determined by its structure
                                                   •      Secretion of receptor
                                                   •      Types of interactions with antigen
                                                   •      Flexibility of hinge region
                                                   •      Bivalency
    Evolution of the immune system           1.    Innate immune system (all multicellular organisms and unifying characteristics)
                                             2.    Adaptive immune system (vertebrates only, unifying characteristics)
                                             3.    Interactions between innate and adaptive immune responses
   Subtopics are numbered, and examples are indicated by round bullets (●). Advanced subtopics are indicated by square bullets (■).

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TABLE III. Immunological techniques
      Foundational Concepts               Subtopics and Examples                                                                               Advanced Subtopics

      Animal models                       1.    Human studies: advantages versus disadvantages                                           Other types of animal models beyond
                                          2.    Brief overview of different animal models that can be used to study immunological         k/o and knock in
                                                concepts                                                                                 Specific model organisms (e.g.,
                                                •      Knock-out                                                                          Drosophila mice, rats, Zebra fish,
                                                •      Knock-in                                                                           Xenopus, C. elegans, humanized
                                                                                                                                          mice)
                                                                                                                                         Non-model organisms
      Cellular techniques                 1.    Overview of sample preparation consideration                                             Next Generation
      considerations                      2.    Overview of assay sensitivity versus specificity                                          Sequencing/bioinformatics
                                          3.    in vitro, ex vivo, in vivo experiments - differences and techniques
                                          4.    Isolation of immune cells from tissue
                                          5.    Flow cytometry (see below)
      Antibodies for research,            1.    Introduction                                                                             CyTOF
      diagnostics, and therapeutics       2.    Generation of antibodies for research and clinical use                                   Noninvasive imaging techniques
                                          3.    Immunoassays                                                                              (luminescence, PET/CT)
                                                •     Pros and cons
                                                •     Overview of technical concepts
                                                •     Interpretation of Results
                                                •

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                                                      Examples
                                                      o      ELISA/EIA/ELISPOT
                                                      o      Western Immunoblot
                                                      o      Immunohistochemistry and immunofluorescence
                                                      o      Microscopic imaging
                                                      o      Flow cytometry (see below)
      Flow cytometry                      1.    Overview of technical concepts                                                           Multiparameter analysis
                                                •      Overview of instrumentation                                                       Statistics and data analysis in
                                                •      Controls for experiments                                                           immunology
                                                •      Sample preparation
                                                •      Data acquisition
                                          2.    Interpretation of results
                                          3.    Cellular analysis versus cell sorting
   Subtopics are numbered, and examples are indicated by round bullets (●). Advanced subtopics are indicated by square bullets (■).

recommendations for curriculum content, as well as additional                                 graduate/medical school level, needs for biotechnology
resources for further classroom enrichment, compiled from a                                   and biomedical careers, and their own teaching experien-
survey of the AAI teaching community. Finally, we as educators                                ces. These resources were selected based on individual
are not only responsible for the scientific content in our courses                            experiences and not from a targeted validation study.
but are also obligated by a responsibility to convey this content                             Absence from the sources cited in this article does not
in an equitable manner to serve a diverse student population as                               reflect an intentional decision against inclusion. In Decem-
effectively as possible. To speak to these principles, we have                                ber 2019, a survey was sent out to all members of the ITIG
included recommendations for antiracist and inclusive teaching                                (203) for initial feedback to the suggested key topics (78
with a few examples of how to translate this desire into peda-                                responses) and to recruit team members (47 volunteered)
gogy. The intent of the AAI Ad Hoc Committee and ITIG mem-                                    to define foundational concepts, determine subtopics, and
bers is to provide a resource for new as well as seasoned                                     identify examples in small working groups. Subsequently,
undergraduate immunology instructors for curriculum develop-                                  in January 2020, working groups were formed with three
ment and curriculum improvement.                                                              or four participants facilitated by one Ad Hoc Committee
                                                                                              member. Each working group included at least one under-
Process of recommendations development                                                        graduate educator and one educator from a graduate
The development of the recommendations was a highly                                           school. From April to May 2020, the Ad Hoc Committee
inclusive and reiterative process (Fig. 1) designed to                                        members compiled the working group recommendations,
ensure that the recommendations would reflect topics that                                     removed redundancies, sequenced the individual topics,
immunologists highly prioritize and bridge undergraduate                                      and uniformly formatted the document. A second survey
and graduate immunology education. In October 2019, the                                       was sent out to the ITIG (10 responses) in June 2020, and
AAI Education Committee formed an eight-member Ad                                             the Ad Hoc Committee further refined the recommenda-
Hoc Committee composed of current and former AAI Edu-                                         tions. Finally, the draft document was shared with the
cation Committee members representing undergraduate,                                          ITIG, and the ITIG was invited to provide written feed-
graduate, and medical school educators as well as a mem-                                      back and participate in a virtual workshop to further dis-
ber of the biotech industry. The Ad Hoc Committee cre-                                        cuss the recommendations. This 3-h workshop (49 ITIG
ated a list of key topics informed by current textbook                                        attendees) took place on July 24, 2020. In breakout ses-
content (11--16), other resources, requirements at the                                        sions dedicated to one or two key topics and facilitated by

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TABLE IV. Innate immunity
   Foundational Concepts                    Subtopics and Examples                                                                             Advanced Subtopics

   Functions of barriers and pre-           1.    Functions of anatomical & chemical barriers                                                 Non-vertebrate innate
   formed elements                          2.    Functions of intrinsic mechanisms                                                            immunity
                                                  •     microRNA                                                                              Regulation of complement
                                                  •     CRISPR                                                                                 activation
                                            3.    Functions of complement (e.g., Ig clearance, MAC)                                           Complement interaction
                                                                                                                                               with coagulation cascade
                                                                                                                                               and kallikrein system
                                                                                                                                              Blood brain barrier

   Innate immune cell types and             1.    Description of cell types                                                                   Developmental origins of
   functions                                      •     Epithelial cells                                                                       tissue resident and
                                                  •     Neutrophils                                                                            infiltrating phagocytes
                                                  •     Macrophages                                                                           Neutrophil extracellular
                                                  •     Dendritic cells                                                                        traps
                                                  •     NK cells                                                                              Maintenance of tissue
                                                  •     Basophils, Eosinophils, Mast cells                                                     homeostasis by macrophage
                                            2.    Characterization of effector functions by innate immune cells                               Apoptosis pathways
                                                  •     Secretion of type I interferons                                                       Innate lymphoid cell
                                                  •     Antimicrobial peptides

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                                                  •     Phagocytosis
                                                  •     Reactive oxygen and nitrogen radicals
                                                  •     Cell death induction

   Differences of innate immunity from      1.    Rapid response time                                                                         Innate memory
   adaptive immunity                        2.    No memory
                                            3.    Generalized recognition of pathogens based on pathogen-associated molecular patterns
                                                  (PAMPs)

   Germline-encoded pattern                 1.    Pattern Recognition Receptors (PRR)                                                         Fungal and protozoan PRR
   recognition receptors                          •     extracellular and intracellular (e.g., TLRs)                                           and PRR ligands
                                                  •     intracellular only (e.g., cytosolic or endosomal -NODs and RIGs)
                                            2.    PRR signaling
                                            3.    PRR ligands
                                                  •     Bacterial
                                                  •     Viral
                                                  •     Host derived
                                            4.    PAMPs
                                            5.    DAMPs

   Dendritic cells                          1.    Survey, capture, migration, and processing of antigens
                                            2.    Presentation of processed antigen to B cells and T cells in secondary lymphoid tissues

 Subtopics are numbered, and examples are indicated by round bullets (●). Advanced subtopics are indicated by square bullets (■).

the Ad Hoc Committee members, the current recommen-                                         Immunology content recommendations
dations were further refined according to the survey com-                                   The format of the recommendations is layered, allowing educa-
ments, and in the following plenary session, a preferred                                    tors to start with key topics of immunology, which are further
sequence of the recommendations was discussed. In                                           broken down into foundational concepts that may be covered
August 2020, the Ad Hoc Committee finalized the curricu-                                    in each section. Key topics represent critical categories recom-
lum recommendations and developed a recommendation                                          mended for inclusion in undergraduate immunology curricula,
for inclusive and antiracist teaching. These materials were                                 and the foundational concepts are embedded beneath the key
then presented in September 2020 to the AAI Education                                       topics as important subcategories. If educators are interested in
Committee, which approved the recommendations with                                          more-specific guidance within the foundational concepts, they
some minor edits and presented them to the AAI Council,                                     can then refer to the subtopics and examples provided. Sub-
which endorsed the recommendations and suggested a                                          topics and examples offer flexible opportunities to elaborate
broader dissemination in November 2020.                                                     and work with students on the foundational concepts.
                                                                                            Advanced subtopics are flexible opportunities to explore con-
The recommendations                                                                         cepts more in depth in accordance with an instructor’s inter-
The curriculum recommendations provided are intended to                                     ests, expertise, and available time. This layered approach
serve a two-fold purpose: the first, to provide guidance for                                provides the instructor with flexibility in how much detail they
immunology content selection and the second, to provide a                                   want to provide and allows the instructor to shape the curricu-
framework for equity in the classroom (17--19). The curricular                              lum according to the needs of their particular undergraduate
content recommendations are presented first (Tables I--XV),                                 students, the length of the module or course, and the
followed by the recommendations for inclusive and antiracist                                instructor’s individual expertise. The examples are intended for
teaching.                                                                                   new educators as a springboard for curriculum development in

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TABLE V. Inflammation
   Foundational Concepts                    Subtopics and Examples                                                                              Advanced Subtopics

   Principles of inflammation               1.    Protective response involving immune cells, blood vessels, protein and lipid-based
                                                  mediators
                                            2.    Beneficial aspects

   Hallmarks of inflammation                1.    Calor, rubor, tumor, dolor, loss of function

   Inflammatory inducers                    1.    Microbial products
                                                        PAMPs (e.g., LPS, bacterial DNA, viral nucleic acid)
                                            2.    Host associated products:
                                                        DAMPs (e.g., ATP, nucleic acids, HMGB1, hyaluronic acid)
                                                        Complement factor C5a

   Intracellular response                   1.    Inflammasome
                                            2.    Pyroptosis

   Inflammatory mediators                   1.    Cytokines (e.g., TNF, IL-1 , IL-6)
                                            2.    Chemokines (e.g., IL-8)
                                            3.    Lipids (e.g., prostaglandins, leukotrienes)

   Local response                           1.    Cells involved

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                                                         Neutrophils
                                                         Monocytes/M1 macrophages
                                                         Endothelial cells
                                            2.    Cell trafficking to the site of inflammation
                                                         P-selectin, integrins
                                                         Margination, rolling adhesion, firm adhesion, transmigration
                                                         IL-8 and chemotaxis

   Systemic response                        1.    Acute phase                                                                                   Basophils
                                                         Hepatocyte involvement                                                                 Mast cells
                                                         CRP                                                                                    Eosinophils
                                                         IL-6
                                            2.    Fever response
                                                         Hypothalamus involvement
                                            3.    Effect on bone marrow
                                            4.    Other symptoms
                                                         Pain
                                                         Loss of appetite
                                                         Malaise

  Down regulators of inflammation           1.    Inhibitory cells
                                                         M2 macrophages
                                                         Treg
                                            2.    Inhibitory biomolecules
                                                         Resolvins
                                                         IL-10
                                                         TGF-

  Anti-inflammatory drugs                   1.    NSAID (aspirin or ibuprofen)
                                            2.    Biologics (anti-TNF)

  Subtopics are numbered, and examples are indicated by roundbullets ( ). Advanced subtopics are indicated by square bullets (   ).

their classroom. They are also intended for seasoned educators                                  be avoided in a subject matter with so many intercon-
as a cross-check to modify course content or to add a new                                       nected facets. In some cases, it was determined that the
module to an existing course. Although the Ad Hoc Committee                                     redundancy was actually important and necessary to rein-
key topics are intentionally arranged in their current order                                    force important topics. Finally, instructors may be limited
based on classroom experience, each key topic is self-standing                                  by the time they have available. Instructors are encour-
and can be taught in any logical sequence according to the                                      aged to prioritize the foundational concepts. For minimum
instructor’s preference. Additionally, content from one key                                     hours available, instructors could choose to only cover
topic may be distributed throughout the semester when                                           material listed in Table II. For a quarter system--based
related content is discussed. This may be most appropri-                                        course, instructors could plan to cover key topics listed in
ate for the final four topics (Tables XII--XV), which have                                      Tables II to X and incorporate the clinical material pre-
clinical relevance that may pique student interest                                              sented in Tables XI to XV in the form of case studies
throughout the course in the form of case studies or active                                     throughout the term, whereas a semester-long standalone
learning projects. Although great effort was taken to                                           immunology course could allow for incorporating all key
remove unnecessary redundancy, some redundancy cannot                                           topics.

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TABLE VI. Development and activation of self-tolerant adaptive immune cells
    Foundational Concepts                    Subtopics and Examples                                                                               Advanced Subtopics

    Antigen receptor structure and           1.    BCR structure
    mechanisms of diversity                        •      Immunoglobulin structure
                                                   •      IgM/IgD coexpression
                                                   •      Structural switch to secreted IgM
                                             2.    TCR structure
                                                   •       α/β chains
                                                   •      γ/δ chains
                                             3.    VDJ recombination
                                             4.    Modifications of immunoglobulins
                                                   •      Somatic hypermutation
                                                   •      Class switching
                                                   •      Affinity maturation
    MHC and antigen presentation to T        1.    Classical antigen processing and presentation
    lymphocytes                                    •      MHC Class I
                                                   •      MHC Class II
                                             2.    Non-classical antigen presentation
                                             3.    Self vs foreign antigen presentation
    Generation and development of B          1.    Clonal selection theory                                                                       ILC development
    and T lymphocytes                        2.    B cell development

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                                                   •      Developmental checkpoints
                                                   •      Negative selection
                                                   •      B1 vs B2 cells
                                             3.    T cell development
                                                   •      Gamma/delta vs alpha/beta
                                                   •      Developmental checkpoints
                                                   •      CD4 vs CD8
                                                   •      Positive (MHC restriction and negative selection)
    Central tolerance mechanisms             1.    Fate of autoreactive B cells
                                                   •      Clonal deletion
                                                   •      Receptor editing
                                             2.    Role of thymic epithelial cells and bone marrow stromal cells dendritic cells in central
                                                   tolerance
                                             3.    Function of Aire transcriptional regulator in T cell and B tolerance
                                             4.    Fate of autoreactive thymocytes
                                                   •      Differentiation into nTregs
    Lymphocyte activation and signal         1.    Co-stimulation for T and B cell activation (signal 2)
    transduction- three signals concept            •      Cell adhesion, synapse formation
                                                   •      Activation of transcription factors in lymphocytes
                                             2.    Cytokine receptor signaling for clonal expansion and differentiation (signal 3)
                                                   •      IL-2 (JAK/STAT)
                                                   •      NF-kB
                                                   •      NFAT
                                                   •      AP1
                                             3.    Regulation of activation
                                                   •      Inhibitory signals from immune checkpoint inhibitors and death receptors
    Peripheral tolerance mechanisms          1.    Necessity of peripheral tolerance                                                             Other Treg types (e.g., Tr1)
                                                   •      Leaky central tolerance                                                                Types and functions of
                                                   •      Peripherally restricted antigens                                                        tolerogenic cell subsets
                                             2.    Phenotype and immunoregulatory functions of Tregs                                              (dendritic cells, types of
                                                   •      Role of FoxP3                                                                           peripheral Aire-expressing
                                                   •      nTregs v iTregs                                                                         cells, B1 and Breg cells,
                                             3.    Mechanisms of B cell and T cell peripheral tolerance                                           MDSCs)
                                                   •      IL-10 and TGF-β                                                                        Mechanisms and
                                                   •      Cytotoxicity                                                                            significance of immune
                                                   •      Cell metabolism regulation                                                              privilege
                                                                                                                                                 Oral tolerance (role of IgA
                                                   •      Clonal deletion
                                                                                                                                                  and microbiome, oral
                                                   •      Anergy
                                                                                                                                                  allergen immunotherapy)
                                                   •      Exclusion                                                                              Maternal tolerance to the
                                                                                                                                                  semi-allogeneic fetus
   Subtopics are numbered, and examples are indicated by round bullets (●). Advanced subtopics are indicated by square bullets (■).

The key topics and their foundational concepts                                                about immunological techniques early in the course is
Table I lists the key topics and their foundational concepts that                             intended to prepare students for the inclusion of primary
were universally identified as critical content for an undergrad-                             research papers. Although educators often express interest
uate immunology course. The foundational concepts are num-                                    in introducing undergraduates to reading and interpreting
bered in the sequence that was deemed to be most conducive                                    scientific research articles, there can be hesitancy that with-
for learning immunology. There was extensive discussion                                       out background in scientific techniques it is difficult to
around some of the key topics, and the rationale for final selec-                             interpret data. Early introduction and reinforcement of key
tion and sequence are highlighted in this article. Teaching                                   techniques open up new possibilities for higher learning in

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TABLE VII. Adaptive immune cell effector function
      Foundational Concepts                     Subtopics and Examples                                                                                  Advanced Subtopics

      Role of dendritic cells in activating     1.    Dendritic cells                                                                                  Outlining differences between
      naïve T cells                                          Conventional                                                                              mice and humans
                                                             Plasmacytoid
                                                2.    Differences between mature and immature DC
                                                3.    Routes of antigen processing by DC
                                                4.    Cross-presentation in DC
                                                5.    PAMPs and DC migration
                                                      a. LPS, flagellin, CpG, dsRNA etc
                                                6.    Delivery of the 3 signals to naïve T cells
      Effector CD4 and CD8 T cells              1.    Overview of CD4 subsets                                                                          Metabolism differences resting
                                                             Th1                                                                                       versus activated T cells
                                                             Th2                                                                                       Calcium flux
                                                             Th17
                                                             Treg
                                                2.    Transcription factors and Stats that control CD4 T cell differentiation
                                                3.    Activities of effector cytokines
                                                             IL-2
                                                             IFN-
                                                             TNF

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                                                             IL-4, IL-5
                                                             IL-17, IL-22
                                                             IL-10, TGF-
                                                4.    CD4 T cell influence on macrophage phenotype
                                                5.    Overview of CD8 T cells
                                                             Tc1
                                                             Tc2
                                                             Regulatory CD8 T cells
                                                6.    Mechanisms of T cell-mediated cytotoxicity (e.g., perforin/granzyme, Fas/FasL,
                                                      TRAIL/DR4, DR5)
      Antibody response                         1.    Types of antigens                                                                                Key cytokine/chemokine
                                                             Exogenous                                                                                 signals for organizing GC
                                                             Endogenous
                                                             Autoantigens
                                                             Haptens
                                                2.    T cell dependent versus T cell independent activation of B cells
                                                3.    Differentiation of B cells into antibody-secreting plasma cell
                                                4.    Germinal center formation and role of Tfh and FDC
                                                5.    Somatic hypermutation, class switching and affinity maturation
      Effector function of antibodies           1.    Antibody isotypes and their functions                                                            Glycosylation of hinge
                                                2.    Antibody activation of complement                                                                Fc-receptor mediated NK
                                                3.    Opsonization                                                                                     activation
                                                4.    Antibody-dependent cell-mediated cytotoxicity (ADCC)                                             Details of IgA secretion
                                                5.    Placental transport                                                                              Monoclonal antibody
                                                6.    Neutralizing antibodies                                                                          production
                                                7.    Mast cell degranulation                                                                          Use of monoclonal antibodies
                                                                                                                                                       versus IVIG
      Adaptive immune response over             1.    Kinetics and course of the response                                                              Primary versus secondary
      time                                      2.    T cell memory                                                                                    memory
                                                             Effector memory                                                                           NK cell memory
                                                             Central memory
                                                             Tissue-resident memory
                                                3.    Humoral memory
                                                             Memory B cells
                                                             Long-lived plasma cells
                                                4.    Regulations of the immune response (e.g., Tregs, IL-10, TGF- , PD1/PDL1, PDL2)
      Subtopics are numbered, and examples are indicated by round bullet points ( ). Advanced subtopics are indicated by square bullet points (   ).

the undergraduate classroom. Tolerance, which is often                                           important for students to put together all of the information
introduced later in an immunology course when autoim-                                            they have learned up to that point before delving more in depth
mune diseases are discussed, was merged with the develop-                                        into the more-complex, clinically relevant topics. Understand-
ment of adaptive immune cells as development is tightly                                          ing the mucosal immune response provides a foundation for
linked to selection of self-tolerant cells. This connection                                      immunizations and, therefore, the topic mucosal immunity was
will allow students to gain a clinical context for develop-                                      placed before the topic on active and passive immunizations.
ment of adaptive immune cells early on.                                                          Tumor immunology follows active and passive immunizations
    The topic, integrated immune response, is intended to allow                                  because of the common principles applicable to generation of
students to construct an understanding of the entire immune                                      tumor immune response and the significance of tumor vaccines.
response as a dynamic and interdependent system. It is                                           In medical school, allergies and hypersensitivities are often

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TABLE VIII. Integrated immune response
     Foundational Concepts                    Subtopics and Examples                                                                         Advanced Subtopics

     Temporal immune response                 1.    Infection/injury                                                                        Idea of lymphocytes as a
                                              2.    Induction of immune response                                                            selectable population in an
                                              3.    Effector phase,                                                                         evolutionary sense
                                              4.    Pathogen/lesion clearance
                                              5.    Exhaustion
                                              6.    Memory phase
     Spatial immune response                  1.    Epithelium
                                              2.    Subepithelial tissue
                                              3.    Regional lymph nodes including germinal centers
     Leukocyte trafficking                    1.    Homing to lymph node and from lymph node into the tissues
                                                           HEV
                                                           LFA-1
                                                           Selectin
                                                           S1P1R
     Sequential activation of immune          1.    Sensor cells                                                                            Th1/Th2 shift in allergy
     cells                                                 Epithelial cells
                                                           Macrophages
                                                           Dendritic cells
                                              2.    ILCs and their cognate activating cytokines

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                                                           ILC1/ IL-12
                                                           ILC2/ IL-33
                                                           ILC3/ IL-23
                                              3.    Differentiation of T cells into Th1, Th2, and Th17 cells
                                              4.    iTreg and mechanisms of immune inhibition
                                                           IL-10, TGF-
                                                           CTLA-4
                                                           PD1/PD1-L
     Leukocyte cross talk                     1.    Interaction of lymphocytes with innate immune cells                                     T cells and NK cells
                                                           B cells (via Ab) and phagocytes, NK cells, and mast cells                        Placental immunology
                                                           Th1 cells and M1 macrophages and DC                                              (establishing implantation:
                                                           Th2 cells and mast cell, eosinophils, and M2 macrophages                         placental trophoblast cells,
                                                           Th17 cells and epithelial cell, myeloid cells                                    uterine NK cells, other
                                                                                                                                            immune cells)
     Immune response to pathogens             1.    Choose two examples to compare and contrast pathogen specific responses according to    Impact of infections on the
                                                    instructor's preference                                                                 fetus and pregnancy
                                                           Examples:
                                                           o      Viruses and obligate intracellular bacteria [NK cells, CTL, antibodies]
                                                           o      Extracellular bacteria [neutrophils, macrophages, Th17 cells, IgG]
                                                           o      Facultative intracellular bacteria [macrophage, Th1, granuloma]
                                                           o      Fungi [macrophage, Th1, Th17]
                                                           o      Protozoan [microbe-specific]
                                                           o      Helminths [eosinophils, Th2, IgE]
     Subtopics are numbered, and examples are indicated by round bullets ( , ). Advanced subtopics are indicated by square bullets ( ).

taught along with autoimmune diseases in a combined                                          advanced subtopics. The subtopics are numbered to show the
approach reflecting the pathophysiological similarities. How-                                sequence deemed to best advance student understanding and
ever, it was felt that for an undergraduate curriculum, autoim-                              learning. Bullets identify subtopics, advanced subtopics, and
mune diseases should be covered as a separate topic because                                  specific examples. The advanced subtopics were contributed by
undergraduate students are still building their knowledge and                                IGIT members according to their in-depth knowledge in a
are not exposed to the depth of clinical experience more typical                             given area, and instructors are encouraged to use advanced sub-
for medical students. To highlight the importance of turning off                             topics from their own specialized area.
the immune response after Ag removal, downregulatory mecha-                                      Table II summarizes the key topic overview and terminology
nisms are taught across the topics. Finally, instead of creating a                           of the immune system, which primarily serves the goal to estab-
separate key topic for the therapy of diseases involving the                                 lish vocabulary and a common ground for all students. Here, stu-
immune system, therapies are embedded where the diseases of                                  dents are introduced to critical components of the immune
the immune system are discussed to reinforce the underlying                                  response at the molecular, cellular, and tissue level and the
pathophysiological mechanisms and frequently used to engage                                  respective terminology. Because immunology is notable for its
the students who are typically genuinely interested in how                                   substantial, and often intimidating, nomenclature, establishing
immunology is applied to treat diseases.                                                     the terminology early is critical for establishing a working
                                                                                             “language” for the remainder of the course. Table III summa-
The subtopics with examples and advanced subtopics for                                       rizes important immunological techniques from molecular and
the foundational concepts for each key topic                                                 cellular in vitro approaches to animal models. Ab-based techni-
We have created tables for each key topic to list the associated                             ques are extensively covered because of their applications in
foundational concepts with subtopics and examples and                                        research, diagnostics, and therapeutics. Flow cytometry is

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TABLE IX. Mucosal immunity
      Foundational Concepts                   Subtopics and Examples                                                                                 Advanced Subtopics

      Organization of the mucosal             1.    Overview of anatomic compartments
      immune system                                       BALT, NALT, GALT, GU
                                                          Waldeyer’s ring with adenoids, palatine, and lingual tonsils
                                                          Isolated lymphoid follicles
                                                          Lamina propria crypts
                                              2.    Mucus components
                                                          Mucins
                                                          Antimicrobial peptides and proteins
                                                          IgA
                                              3.    Difference between systemic and mucosal lymph nodes
                                                          Peyer’s Patches
                                                          Mesenteric lymph nodes
                                                          Cryptopatches
                                                          Appendix
                                                          Cecum
                                              4.    High endothelial venules

      Specialized immune cells located at     1.    Activation state of lymphoid cells in the area                                                 Activation markers on resident
      mucosal sites                           2.    Mast cells and other innate cells present                                                      B and T lymphoid cells

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                                              3.     / T cells                                                                                     Innate lymphoid cells (ILC)
                                              4.    Plasma cells (IgA secreting)                                                                   MAIT
                                                                                                                                                   Intraepithelial lymphocytes
                                                                                                                                                   (CD8)
                                                                                                                                                   CD8 + T cells
                                                                                                                                                   Activities of / T cells

    Unique APC populations and               1.    Overview of APC present                                                                         CD103+ DCs
    uptake of antigen at mucosal sites                   Lack of inflammatory receptors
                                                               o      TLR, FcR, CD14
                                                         Lack of inflammatory cytokines
                                                               o       IL-1 , TNF
                                             2.    Role of M cells
                                             3.    Antigen transport across epithelium
                                             4.    Lumenal access of DCs

    Role of IgA in protection at mucosal     1.    IgA secretion by plasma cell on basolateral side of epithelial surface                          IgA deficiency and transport of
    sites                                    2.    Transcytosis of IgA to apical face of epithelial cell via poly-Ig receptor                      IgM
                                             3.    IgA’s role in the mucosa/with mucin                                                             Role of secretory IgA
                                                                                                                                                   component
    Induction and regulation of the          1.    Initiation of the response in mucosal sites                                                     Differences between gut and
    immune response at mucosal sites         2.    Reasons for limited inflammation                                                                lung mucosal immune
                                             3.    Role of Tregs                                                                                   responses
                                                           Tregs control T cells with inflammatory potential                                       Pathology at mucosal sites,
                                             4.    Tolerance to non-pathogenic substances (e.g.. food)                                             examples:
                                             5.    Tolerance to normal microbiota                                                                        Inflammatory bowel
                                                                                                                                                         disease
                                                                                                                                                         Antibiotic use and C.
                                                                                                                                                         difficile
                                                                                                                                                         Defense against
                                                                                                                                                         helminths
                                                                                                                                                         Asthma
                                                                                                                                                         Food allergy
                                                                                                                                                         IgA deficiency
                                                                                                                                                         Bacterial vaginosis

    Subtopics are numbered, and examples are indicated by round bullets ( , ). Advanced subtopics and their examples are indicated by closed square bullets ( ) and
    open square bullets ( ), respectively.

included because it is a commonly used technique that is central                                 created with primarily bacterial and viral infections in mind;
to immunology findings described throughout each topic. There                                    thus, innate responses to fungal and protozoan microbes are
was strong consensus to introduce immunological techniques as                                    listed as advanced subtopics, reflecting instructional directions
a dedicated key topic early in the course to provide students                                    that are traditionally less common in curricula. In addition to
with a robust basis for understanding primary immunology                                         complement, phagocytic cells, and NK cells, epithelial cells are
research papers throughout the course.                                                           included as effector cells in the innate immune response as
    Table IV summarizes the key topic innate immunity. As one                                    they exemplify how different cell types and tissues, not tradi-
of the major conceptual “arms” of the immune system, this key                                    tionally considered part of the immune system, can play key
topic helps frame an understanding of how the organs and cel-                                    roles in immunity. Table V summarizes the key topic inflamma-
lular systems first recognize and combat potentially dangerous                                   tion. It is recommended that instructors also highlight the ben-
microbial or environmental encounters. This key topic was                                        eficial aspects of inflammation and begin this key topic with a

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TABLE X. Active and passive immunizations
    Foundational Concepts                     Subtopics and Examples                                                                         Advanced Subtopics

    Historical aspects of immunization        1.    Variolation                                                                              Implications of von
                                              2.    Jenner’s Experiments with smallpox                                                       Behring’s discovery of
                                              3.    Development of the polio vaccine                                                         diphtheria anti-toxin
                                                                                                                                             Smallpox eradication
                                                                                                                                             campaign
                                                                                                                                             Cutter labs
    Why vaccines work and concept of          1.    Statistics of safety versus morbidity/mortality of infectious disease
    herd immunity                                          Any example would work
                                              2.    R0 and herd immunity thresholds
                                                           Measles
                                              3.    Rationale for targeting specific vaccines to particular populations
                                                           Age dependency
                                                           Pregnant mothers
                                                           Career associated exposure (e.g., veterinarians, military)
                                                           Prevalence of a disease in regards to global vaccination
    Types of vaccines                         1.    Whole killed organism vaccines
                                              2.    Live-attenuated organism vaccines
                                              3.    Toxoid vaccines
                                              4.    Subunit vaccines

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                                              5.    Recombinant vaccines
                                              6.    Polysaccharide vaccines
                                              7.    Nucleic acid-based vaccines
    Important aspects of vaccines             1.    Advantages and Disadvantages of the vaccines listed above
                                              2.    Type of immune response initiated for each vaccine listed above
                                                           Humoral immunity
                                                           Humoral and cell mediated immunity
                                              3.    Example of different flu vaccine types can initiate different types of immunity (live
                                                    attenuated influenza vaccine versus the quadrivalent flu vaccine)
    Vaccine production, adjuvants and         1.    Vaccines preparation
    preservatives                             2.    Route of administration
                                              3.    Common vaccine adjuvants (e.g. thimerosal, aluminum)
                                                           Purpose (depot effect, inflammasome activation)
                                                           Toxicities
                                                           Mechanism of action
                                              4.    Vaccine preservatives
    Challenges of vaccine success             1.    Technological difficulties associated with vaccine development
                                                           Example: influenza vaccines and seasonal variability
                                              2.    Microbial limitations for making vaccines
                                                           Example: HIV vaccine and high mutation rate
                                              3.    Societal and global challenges to achieve R0 levels required to generate herd immunity
                                                           Anti-vaccine movement
                                                           Example: Polio and global challenges for eradications
    Passive immunization                      1.   Use of pre-formed antibodies versus active immunization
                                                          Advantages/disadvantages
                                                          Half-life of preparations
                                                          Mechanism of action
                                             2.    Polyclonal and monoclonal antibody preparations
                                                          Medical examples of how passive immunization is used (e.g., tetanol)
                                             3.    Differences of immune globulin, specific immune globulin, and intravenous IG
                                             4.    Natural examples of passive immunization (e.g., maternal antibodies via crossing the
                                                   placenta or breast feeding)
    Subtopics are numbered, and examples are indicated by round bullets ( ). Advanced subtopics are indicated by square bullets ( ).

discussion of the protective aspects of acute inflammation.                                        Table VII summarizes the key topic adaptive immune cell
Inflammation leads to initiation of the adaptive immune                                        effector function. Dendritic cells, effector CD4 and effector
response, and thus, this key topic is followed by the key topic                                CD8 T cells, Ab response, and Ab function are first examined,
development and activation of self-tolerant adaptive immune                                    and then the adaptive immune response over time is described.
cells, which is summarized in Table VI. The concept of toler-                                  Germinal centers and NK cell functioning can be explored as
ance is introduced under this key topic because the develop-                                   advanced subtopics. Table VIII summarizes the key topic inte-
ment of lymphocytes is tightly linked to tolerance. The                                        grated immune response, which aims to provide students with
importance of self-tolerance for lymphocyte development is                                     a general understanding of how the innate and adaptive
also reflected in the title of this key topic. Instructors who                                 immune responses interweave over time. This section also
want to highlight oral tolerance or tolerance in pregnancy may                                 defines the locations where the interactions between Ag, innate,
wish to introduce these advanced topics here.                                                  and adaptive immune cells take place throughout the course of

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TABLE XI. Tumor immunology
      Foundational Concepts                    Subtopics and Examples                                                                           Advanced Subtopics

      Tumor immunosurveillance                       Examples of tumor antigens                                                            Role of immune cells in promoting
                                               1.
                                                          Aberrant or overexpression of normal proteins                                    tumor -chronic inflammation
                                                                                                                                           Modifiable host factors affecting
                                                          Differentiation antigens
                                                                                                                                           tumor immunity (e.g., diet,
                                                          Viral antigens
                                                                                                                                           microbiota)
                                                          Antigens expressed by mutated passenger/driver mutations
                                               2.    Anti-tumor immune mechanisms
                                                            Tumor killing by cytotoxic CD8 T cells
                                                            Cross-presentation of tumor antigens to CD8 T cells by dendritic cells
                                                            Humoral antitumor responses
                                                            NK-mediated killing of tumor cells
                                                            Role of activated macrophages in tumor suppression
      Immune escape by tumors                 1.     The three Es of immunoediting                                                         Clinical evidence of the presence of
                                                            Elimination                                                                    immune cells in the tumor
                                                            Equilibrium                                                                    microenvironment (tumor biopsies)
                                                            Escape                                                                         and the relevance of ‘immunoscore’ to
                                              2.     Escape mechanisms                                                                     assess prognosis (hot vs cold tumors)
                                                             Loss of tumor antigens                                                        Co-opting of immune cells by tumors,
                                                            Immunosuppressive tumor microenvironment                                       especially tolerogenic mechanisms

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                                                            o      Abnormal vasculature and hypoxia                                        like recruitment of Tregs and
                                                            o      Role of immune check points on CD8 and regulatory T cells (PD-          changing the orientation of
                                                                   1/CTLA-4)                                                               macrophages to wound-healing mode
                                                            o      Tumor secreted immunosuppressive cytokines/growth factors               Co-opting of stromal cells including
                                                                   (TGF- /VEGF                                                             the cancer-associated fibroblasts by
                                                            o      Suppressive myeloid cells (M2 macrophages, myeloid-derived              tumor cells
                                                                   suppressor cells, tolerogenic dendritic cells)
      Cancer immunotherapy                    1.     Brief history of cancer immunotherapy                                                 Example of one of the successful
                                                            1854 – Virchow                                                                 clinical trials of PD-1/CTLA-4 or
                                                            1883 – Fehleisen                                                               CAR-T
                                                            1891 – Coley
                                                            1909 – Ehrlich
                                              2.     Classes of cancer immunotherapy
                                                            Tumor-targeting monoclonal antibodies (e.g., anti-CD20, anti-Her2)
                                                            Cytokine therapy (e.g., high dose IL-2 and IFN-
                                                            Tumor vaccines (e.g., dendritic cell-based vaccine in prostate cancer)
                                              3.     T-cell based agents
                                                            T cell checkpoint inhibitors (anti-PD1 and anti-CTLA4)
                                                            Adoptive cell therapies (CAR-T
                                                            NK cell therapy
                                              4.     The rationale for combinatorial therapies
      Subtopics are numbered, and examples are indicated by round bullets ( , ). Advanced subtopics are indicated by square bullets ( ).

the immune response. To highlight that the immune response                                     because many novel approaches of cancer immunotherapy
to pathogens is tailored to the specific type of pathogens, the                                employ mechanisms of active and passive immunization.
immune responses to two different pathogens could be com-                                      The key topic tumor immunology first explores mechanisms
pared and contrasted according to the instructor’s expertise. It                               of tumor surveillance, then investigates tumor escape from
is highly recommended that instructors choose pathogens that                                   the immune response, and concludes with subtopics on can-
are relevant or well-known to the students.                                                    cer immunotherapy.
    Table IX summarizes the key topic mucosal immunity,                                            The remaining four key topics are dedicated to pathology
which examines the immune response in the mucosa with spe-                                     associated with the immune system, and each include therapeu-
cial attention paid to the gut mucosa. Here, examples for patho-                               tic interventions as a foundational concept. Table XII summa-
logical conditions affecting the mucosa can be introduced as                                   rizes the key topic allergies and hypersensitivities. With a
advanced subtopics. Many types of immunizations target the                                     reference to the medical school curriculum, hypersensitivities
mucosal immune system. Thus, the key topic active and passive                                  are first introduced as pathological responses to Ag that can be
immunizations, summarized in Table X, follows the key topic                                    classified as allergies, autoimmunity, and transplant rejection.
mucosal immunity. A brief historical overview and a descrip-                                   Thereafter, hypersensitivities are classified based on the under-
tion of parameters for vaccine success have been included as a                                 lying mechanism according to the Gell--Coombs classification
foundational concept to increase awareness of the complexity                                   more consistent with the undergraduate immunology curricu-
and difficulty of developing a protective vaccine. Passive immu-                               lum, and the remainder of the key topic follows this classifica-
nization is focused on Ab-related subtopics. Table XI summa-                                   tion. Table XIII summarizes the key topic autoimmune
rizes the key topic tumor immunology. This key topic                                           diseases. The foundational concepts include causes and epide-
follows the key topic active and passive immunizations                                         miology of autoimmune diseases and a classification based on

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TABLE XII. Allergies and hypersensitivities
     Foundational Concepts                 Subtopics and Examples                                                                                   Advanced Subtopics

     Immunological hypersensitivities,     1.    General definition of immunological hypersensitivities and contrast to non-
     definition and classification               immunological hypersensitivities
                                                       Role of sensitization
                                           2.    Classification of immunological hypersensitivities based on antigen types
                                                       Allergies (pathological responses to harmless environmental antigens)
                                                       Autoimmunity (pathological responses to self-antigens)
                                                       Graft rejection/transfusion reactions (pathological responses to alloantigens)
                                           3.    Classification of immunological HS based on mechanism (Gell-Coombs classification)
                                                       Primarily antibody-mediated via IgE (Type 1) and IgG/IgM (Types 2 and 3)
                                                       T cell-mediated via inflammatory and cytotoxic T cells (Type 4)
    Main allergic reaction types          1.       “Classical” allergies (Type 1 HS, IgE-mediated)                                               Recognizing anaphylactic
    according to the Gell-Coombs                          Role of mast cells, histamine, eicosanoids                                             reactions
    classification                                        “Immediate”, biphasic pattern (early and late phase)                                   Hygiene hypothesis
                                                          Anaphylaxis                                                                            Role of early exposure to
                                                          Atopy definition: genetic predisposition to IgE hyper-responsiveness                   allergens
                                                          Examples (based on student interest):                                                  The skin-prick test and serum
                                                          o     Hay fever                                                                        IgE testing for diagnosis of
                                                          o     Acute asthma                                                                     allergy diagnosis
                                                          o     Eczema

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                                                          o     Food and drug allergies                                                          IgG-mediated allergies (Type 2
                                                          o     Insect bites                                                                     and 3 hypersensitivities):
                                            2.     T cell-mediated allergies (Type 4 hypersensitivity reactions):                                cytotoxic and cytolytic effects,
                                                          Delayed-type reactions                                                                 inflammation with examples
                                                          Inflammatory (Th1, Th2, Th17-mediated) and/or cytotoxic reactions                      (typically drug-induced):
                                                                                                                                                        Penicillin (hemolytic
                                                          Examples:
                                                                                                                                                        disease)
                                                          o     Contact dermatitis
                                                                                                                                                        Biologicals (serum
                                                          o     Chronic asthma
                                                                                                                                                        sickness)
                                                          o     Stevens-Johnson syndrome
    Principles of therapy of allergic       1.     Drugs used to treat allergic reactions                                                        Epinephrine and use of Epi pens
    reactions                                             Anti-histamines
                                                          Corticosteroids
                                                          Bronchodilators (rescue inhalers)                                                      Allergen desensitization
                                            2.     Allergen immunotherapy (desensitization strategies)                                           protocols
    Subtopics are numbered, and examples are indicated by closed round bullets ( ). Advanced subtopics are indicated by square bullets ( ). Examples for specific
    diseases and drugs are indicated by open bullets ( , ).

their underlying mechanism. It is strongly recommended                                      eliminating institutional racism and structural inequality (19).
that instructors choose clinical examples for autoimmune                                    Inclusivity in science education means expanding access to
diseases based on student interest. Table XIV summarizes                                    educational and professional opportunities to underrepresented
the key topic transplant rejection and includes references                                  groups and crafting our teaching in a way that specifically
to both organ transplants and blood transfusions. Finally,                                  acknowledges and engages all learners and validates their indi-
Table XV summarizes the key topic immunodeficiencies,                                       vidual and collective experiences. Our teaching practices must
which are presented as primary and secondary immunode-                                      be informed by not only our students’ personal histories but
ficiencies. As time permits and according to instructor                                     also the history and dynamics of how their world is and was
expertise, one or more examples for each type of immuno-                                    shaped before their arrival into our classroom.
deficiency can be presented. Diagnostic assessments used                                        As educators, we hope to empower the next generation
for both primary and secondary immunodeficiencies are                                       through knowledge and agency. As educators in the scien-
included here and may be a tool to reinforce immunologic                                    ces, we have a responsibility to ensure that all of our schol-
                                                                                            ars from diverse backgrounds—representing individuals
techniques described earlier in Table III.
                                                                                            who differ in racial, cultural, and ethnic identity; gender
                                                                                            identity; sexual orientation; age; physical and intellectual
Recommendations for inclusive and antiracist teaching                                       disability; spiritual beliefs; and socioeconomic status—will
Our society is undergoing transformative changes in the aware-                              have an opportunity to contribute to the scientific enter-
ness of institutional racism and structural inequality that limit                           prise. Students in an immunology course typically come
the participation of all. It is imperative to recognize the need to                         academically prepared by having completed prerequisite
include different perspectives in solving scientific problems.                              courses in general biology and general and organic chemis-
Yet it is not enough to enable all to come to the table where                               try. However, their life stories and their living circumstan-
decisions are made; rather, it is time to reconstruct this table,                           ces at the time they take your immunology course will vary
collaboratively informed by all participants’ vision in our soci-                           widely. Some students might be caregivers or breadwinners,
ety. We, as educators, have an opportunity to take part in                                  live in crowded quarters, and may have grown up doubting

https://doi.org/10.4049/immunohorizons.2100030
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