Primary immunodeficiencies (PIDs) comprise a heterogeneous group of more than 400 genetic disorders that result in defects in the immune response152. Bruton, O. C. Agamma-globulinemia. Rev. Nat. Virus-based therapy was introduced in the 1990s with the use of adenovirus, but only in recent years has it been used in practice in the clinic. Waisman, A., Lukas, D., Clausen, B. E. & Yogev, N. Dendritic cells as gatekeepers of tolerance. The data indicate that the therapy is well tolerated and has led to increased patient survival in some trials. CAS Annu. One of the problems to be solved is the immune tolerance developed to elements delivered by the oral route, but some vaccines are already effectively administered by this route (such as the oral polio, cholera, typhoid fever and rotavirus vaccines). Some lymphocytes escape control due to polymorphisms in several genes that affect the routes of lymphocyte activation. Exp. Nature 388, 394397 (1997). Adaptive immunity is clearly based on the specific recognition of antigenic determinants by somatically diversified receptors (B cell and T cell receptors (BCR and TCRs, respectively)) and on its capacity to respond more effectively to restimulation with the same antigen. J. Clin. Shitara, K. & Nishikawa, H. Regulatory T cells: a potential target in cancer immunotherapy. Proliferating dendritic cell progenitors in human blood. A large number of genes have been found to affect the pathways/mechanisms involved in macrophage and B-cell differentiation and lymph node development, among many functions. Tfh cells are very important for germinal center reactions, antibody class switching, affinity maturation, and the development of high affinity antibodies and memory B cells51,52. ILC are mainly involved in early protection against viruses and bacteria13,21, but their response to dysregulated local proinflammatory cytokine production in adipose tissues leads to the development of metabolic disorders and obesity20. Immunol. 48, 948955 (2020). However, PIDs are broadly classified as follows according to the component of the immune system affected: T-cell immunodeficiency, e.g., defects in the IFN-/IL-12 pathway and mutations in the autoimmune regulator (AIRE) gene. 188, 37343744 (2012). Nat. Ubiquitination is a process that marks proteins for degradation via the proteasome, which is required for the processing of intracellular antigens (such as virus proteins or mutated tumor proteins) and their presentation by class I HLA molecules. Lopez-Vergs, S. et al. factors These factors trigger a break in self-tolerance with the activation of self-reactive lymphocytes through several mechanisms, such as molecular mimicry, the overexpression and abnormal expression of MHC class II molecules in peripheral tissues, thymic aging, and immunodeficiencies (discussed below) and many others. Silverstein, A. M. Autoimmunity versus horror autotoxicus: the struggle for recognition. Kiessling, R., Klein, E., Pross, H. & Wigzell, H. Natural killer cells in the mouse. Fong, L. & Engleman, E. G. Dendritic cells in cancer immunotherapy. tremendous role of International Union of Immunological Societies (IUIS) and its Expert Committee updating categorization of IEI approximately every 2 years. Thus, most mAbs currently used in clinical applications are linked to radioactive elements and used for diagnostic purposes (Table2). Human NK cells: surface receptors, inhibitory checkpoints and translational applications. Other sources, such as circulating or skin dendritic cells, are relatively scarce and are therefore not usually used. & Todd, J. Guia, S. & Narni-Mancinelli, E. Helper-like innate lymphoid cells in humans and mice. Slider with three articles shown per slide. Cancer Res. frica Gonzlez-Fernndez. New effector CD4+ helper T-cell subsets (initially classified as Th1 and Th2)39,40 have been recently described, and at least six human Th cell subsets have been identified to date: Th1, Th2, Th17, Tfh, Th9, and Th22 cells38,41. Immunosenescence and its hallmarks: how to oppose aging strategically? Immune-mediated illnesses comprise a wide variety of diseases characterized by the dysregulation of a normal immune response. Antibodies can block some membrane receptors and avoid cellactivation/proliferation activation/proliferation243,245. Jru, I. Update on the genetics of autoinflammatory disorders. Commun. This long journey has been possible due to the efforts of numerous researchers (throughout the centuries), who have contributed with their work, creativity, successes and failures to advance our knowledge of the immune system, cellular components, membrane markers, interactions, signaling pathways and many more aspects. Other regulatory populations have also been described, including Bregs and CD8+ Tregs, which are the analogous counterparts of Tregs72,73,74. In addition to the use of convalescence plasma, hyperimmune globulin therapy or monoclonal antibodies directed against the virus have also been proposed, and clinical assays are ongoing. Joo, C., Negi, V. S., Kazatchkine, M. D., Bayry, J. Nat. Rev. Ed. Immunology 155, 283284 (2018). Chapters & Volumes. Immunol. Maggi, L. et al. In addition to cancer, cellular immunotherapy has a long history of use against autoimmunity, infectious diseases, allergies and transplantation rejection. Rev. Next generation antibody drugs: pursuit of the high-hanging fruit. Complementarity and redundancy of IL-22-producing innate lymphoid cells. Carter, P. J. Curr. Transl. Examples are etanercept and abatacept (CTLA-4 Ig), which were approved by the European Medicines Agency in 2000 and 2007, respectively. PubMed Central & Benacerraf, B. The development of many different mAbs has enabled the identification of new molecules and the development of more accurate diagnostic approaches; specific, fast and inexpensive technologies; processes for the purification/concentration of compounds; and better and more specific therapy. Inflammatory or innate immune regulators. Ther. 338, 640644 (1998). Moreover, because of recently acquired genomic data, new human polymorphisms have been discovered, some of which play roles in changing immunoglobulin levels, seroconversion rates or the intensity of antigen-specific immune responses. 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Moreover, CD4+ T cells exhibit cytotoxic features in centenarians; this is an acquired characteristic for CD4+ T cells that usually have helper, but not cytotoxic functions under physiological conditions180. The National Vaccine Advisory Committee at 30: impact and opportunity. Complement defects (deficiency in early, late or regulatory complement components)158. Hundreds of vaccines against SARS-Cov-2 (using different strategies such as live attenuated or inactivated pathogens, viral vector-based, viral RNA, DNA, recombinant proteins, peptides, etc. & Lum, L. G. Cancer immunology and immunotherapy. Med. 8, 1125 (2017). Detailed coverage of this topic is beyond the scope of this review, and we refer the reader to recent reviews that provide more information on the biology of human32 and mouse33,34 ILCs. For example, reovirus against brain tumors (alone or combined with other therapies)196 or Maraba virus against triple-negative breast tumors197,198 offer some hope to patients with these types of cancer. Mol. Currently, vaccines are among the factors that, together with hygiene, antibiotics and surgery, save the most lives181. 411, 24752479 (2019). Thus, the main challenges with oncolytic viruses are addressed by improving their antitumoral efficacy, including the optimization of viral delivery, the development of OVs engineered to activate the immune system (e.g., by releasing cytokines), and their use as adjuvant therapies or in combination with other immunotherapeutic agents, such as immunomodulators331. 24, 707712 (2012). Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma. & Hughes, C. C. W. Of mice and not men: differences between mouse and human immunology. Immunity 42, 607612 (2015). & Fuente, M. Chronobiology of the neuroimmunoendocrine system and aging. 50, 13661374 (2018). These modified T cells can directly recognize tumor cells without required antigen processing or presentation by professional antigen-presenting cells. CAS N. Engl. Genes in this group include ADA2 (adenosine deaminase 2), TNFRSF11A (TNF receptor superfamily member 11a), ADGRE2 (adhesion G protein-coupled receptor E2), TRNT1 (tRNA nucleotidyltransferase 1), LACC1 (laccase domain-containing 1) and AP1S3 (adaptor related protein complex 1 subunit sigma 3)159. Advances in Immunology - SCI Journal The three main subsets of T cells carrying / receptor are the CD4+T helper cells and CD8+cytotoxic and CD4+ CD25+ regulatory T cells38. Immunol. In addition to these features, chronic inflammation is considered the key that underlies the phenomenon called inflammaging, which is related to elevated self-reactivity and results in the typical chronic low-grade, systemic inflammatory phenotype observed in the elderly in the absence of acute infection. Martinez-Quintanilla, J., Seah, I., Chua, M. & Shah, K. Oncolytic viruses: overcoming translational challenges. Other initiatives, such as the generation of immunodeficient mice in which human bone marrow or libraries of recombinant phages carrying human variable genes were reconstituted, allowed the development of more fully human antibodies (Table2). Opin. Immunol. CD8+ cytotoxic T cells express the dimeric CD8 marker and have specific lytic capacity to target cells through several mechanisms, including the release of cytotoxic granules, secretion of cytokine tumor necrosis factor alpha (TNFa) and interferon gamma, and the induction of cell death through the interactions of Fas and the Fas ligand38,66. & Akira, S. Pattern recognition receptors and inflammation. Seidel, J. Immunol. Mosmann, T. R. & Sad, S. The expanding universe of T-cell subsets: Th1, Th2 and more. Rankin, L. C. et al. Honda, K. & Littman, D. R. The microbiota in adaptive immune homeostasis and disease. Since the first report of a link between chromosome 11q12 and atopy in 1989163, knowledge about the common risk variants for allergic diseases has increased exponentially, mainly because of GWAS. 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Extensive research has focused on deciphering the role of ILCs to ensure the maintenance of tissue homeostasis and immune protection11,18. Pathol. Similar to other treatments, these approaches require further study, but it is feasible that they may become reality in the near future. Immunol. Front. Immunol. ILC3s are abundant in mucosal tissues, and NCR2+ ILC3s have been proven to be essential for regulating the balance between commensal and pathogenic bacteria through the production of IL-2224. Genome Med. 102, 6174 (2009). Curr. This situation changed because of one of the latest revolutions in antitumor therapy, the development of T lymphocytes that carry a chimeric antigen receptor (CAR) based on a specific antibody directed to a target surface molecule299,300. Cell 89, 587596 (1997). Thus, vaccines are used for cases of allergies, cancers and autoimmune diseases. Improvements in the half-lives of vaccines, for example, by lyophilization, while maintaining immunogenicity is expected to reduce current problems, especially those involved in the transportation of vaccines to remote areas316. & Milner, J. D. Genetics of allergy and allergic sensitization: common variants, rare mutations. U.S.A. 112, 80468051 (2015). Impact Factor of Advances in Immunology, impact factor 2021 | Journal Sci. Genome Med. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. 9, 1740 (2018). In contrast, innate immune responses have traditionally been considered nonspecific and without the capacity to adapt81. In addition, tumor cells create an inhibitory microenvironment around them. However, recent advances in molecular biology have shown that host genes play major roles in infection, together with a wide range of environmental variables127. 22, 680690 (2016). 17, 179186 (2016). 1). In addition, the expression of viral antigens induces an antiviral immune response that helps destroy tumor cells. Drugs 76, 147154 (2016). A. The key of immunosurveillance is cancerous cell expression of tumor antigens that can activate various immune cell phenotypes; for simplicity, any overexpressed, mutated, dysregulated, or rearranged gene product expressed by a cancerous cell may be considered a tumor antigen. Examples of immunotherapy, including the use of vaccines, monoclonal antibodies, fusion proteins, bacteria, oncolytic viruses, cytokines, and different types of cellular immunotherapy: chimeric antigen receptor (CAR) T cells, dendritic and mesenchymal cells, tumor-infiltrating lymphocytes, regulatory (Treg) and gamma/delta (T/) T cells, lymphocyte activated killer (LAK) and natural killer (NK) cells. Kuus-Reichel, K. et al. Blood 135, 656667 (2020). J. Immunol. Immunol. )323 are now under development, and some are in clinical trials.