Key concepts in immunology.

Vertebrates have developed systems of immune defence enabling them to cope with the constant threat posed by environmental pathogens. The mammalian immune system represents a multilayered defence system comprising both innate and adaptive immune responses, characterized by the increasing complexity of their antigen-recognition systems. The discovery of the intimate relationship between innate and adaptive responses has paved the way to a novel understanding of the basic mechanisms governing the regulation of an immune response. The purpose of the present review is to briefly describe the basic immunological concepts that constitute the founding principles of modern vaccinology in humans.

[1]  J. Cerottini,et al.  Specific in vitro Cytotoxicity of Thymus-derived Lymphocytes sensitized to Alloantigens , 1970, Nature.

[2]  P. Matzinger.  The Danger Model: A Renewed Sense of Self , 2002, Science.

[3]  H. Rammensee,et al.  Autophagy promotes MHC class II presentation of peptides from intracellular source proteins , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[4]  B. Lemaître,et al.  The Dorsoventral Regulatory Gene Cassette spätzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila Adults , 1996, Cell.

[5]  R. A. Ezekowitz,et al.  Phagocytosis: elegant complexity. , 2005, Immunity.

[6]  Urs Christen,et al.  CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes , 2003, Nature.

[7]  A. Bowie,et al.  Viral evasion and subversion of pattern-recognition receptor signalling , 2008, Nature Reviews Immunology.

[8]  M. A. Saper,et al.  Structure of the human class I histocompatibility antigen, HLA-A2 , 1987, Nature.

[9]  N. Shastri,et al.  Class I MHC presentation of exogenous soluble antigen via macropinocytosis in bone marrow macrophages. , 1995, Immunity.

[10]  S. Zheng,et al.  Natural and TGF-beta-induced Foxp3(+)CD4(+) CD25(+) regulatory T cells are not mirror images of each other. , 2008, Trends in immunology.

[11]  Jun Zhang,et al.  Sites of specific B cell activation in primary and secondary responses to T cell‐dependent and T cell‐independent antigens , 1991, European journal of immunology.

[12]  A. Rudensky,et al.  Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice , 2007, Nature Immunology.

[13]  Hao Shen,et al.  Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory , 2003, Science.

[14]  F. Burnet.  A modification of jerne's theory of antibody production using the concept of clonal selection , 1976, CA: a cancer journal for clinicians.

[15]  Z. Janowicz,et al.  A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine. , 2006, Vaccine.

[16]  G. McFadden,et al.  Tumor necrosis factor and interferon: cytokines in harmony , 2008, Current Opinion in Microbiology.

[17]  P. Hodgkin,et al.  The clonal selection theory: 50 years since the revolution , 2007, Nature Immunology.

[18]  Joanna M. Roberts,et al.  In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2 lymphocyte differentiation , 2008, Proceedings of the National Academy of Sciences.

[19]  R. Maldonado-López,et al.  CD8α+ and CD8α− Subclasses of Dendritic Cells Direct the Development of Distinct T Helper Cells In Vivo , 1999, The Journal of experimental medicine.

[20]  M. Toda,et al.  Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. , 1995, Journal of immunology.

[21]  J. Lieberman,et al.  Death by a thousand cuts: granzyme pathways of programmed cell death. , 2008, Annual review of immunology.

[22]  S. Akira,et al.  Pathogen Recognition and Innate Immunity , 2006, Cell.

[23]  P. Chomez,et al.  GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives , 2007, Expert review of vaccines.

[24]  C. Murre.  Epigenetics of antigen-receptor gene assembly. , 2007, Current opinion in genetics & development.

[25]  Ying Wang,et al.  A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 , 2005, Nature Immunology.

[26]  P. A. Peterson,et al.  Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. , 1994, Science.

[27]  James E. Evans,et al.  Molecular identification of a danger signal that alerts the immune system to dying cells , 2003, Nature.

[28]  C. Janeway,et al.  A human homologue of the Drosophila Toll protein signals activation of adaptive immunity , 1997, Nature.

[29]  M. Nolte,et al.  Inflammatory signals in dendritic cell activation and the induction of adaptive immunity , 2009, Immunological reviews.

[30]  P. Loetscher,et al.  Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function , 2000, The Journal of experimental medicine.

[31]  M. Moser,et al.  CD4+ CD25+ Regulatory T Cells Control T Helper Cell Type 1 Responses to Foreign Antigens Induced by Mature Dendritic Cells In Vivo , 2003, The Journal of experimental medicine.

[32]  Michael Karin,et al.  Intracellular pattern recognition receptors in the host response , 2006, Nature.

[33]  Jonathan W. Yewdell,et al.  Rapid degradation of a large fraction of newly synthesized proteins by proteasomes , 2000, Nature.

[34]  A. Shaw,et al.  Triggering TLR signaling in vaccination. , 2006, Trends in immunology.

[35]  R. Poljak,et al.  Three-dimensional structure of immunoglobulins. , 1979, Annual review of biochemistry.

[36]  Federica Sallusto,et al.  Follicular B Helper T Cells Express Cxc Chemokine Receptor 5, Localize to B Cell Follicles, and Support Immunoglobulin Production , 2000, The Journal of experimental medicine.

[37]  M. Goldman,et al.  The multiple facets of toll-like receptors in transplantation biology. , 2008, Transplantation.

[38]  R. Zinkernagel,et al.  A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. , 2000, Science.

[39]  E John Wherry,et al.  Generation and maintenance of immunological memory. , 2004, Seminars in immunology.

[40]  M. Kovacsovics-Bankowski,et al.  A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules , 1995, Science.

[41]  M. Bevan,et al.  CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection , 2004, Nature Immunology.

[42]  Amer A. Beg,et al.  An Essential Role of the NF-κB/Toll-Like Receptor Pathway in Induction of Inflammatory and Tissue-Repair Gene Expression by Necrotic Cells1 , 2001, The Journal of Immunology.

[43]  C. Milstein,et al.  Memory in the B-cell compartment: antibody affinity maturation. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[44]  M. Cohen.  Fundamental Immunology, 6th Edition , 2009 .

[45]  Defining protective responses to pathogens: cytokine profiles in leprosy lesions. , 1991, Science.

[46]  S. Hansen,et al.  Duration of antiviral immunity after smallpox vaccination , 2003, Nature Medicine.

[47]  C. Snapper,et al.  B‐cell activation by T‐cell‐independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms , 2000, Immunological reviews.

[48]  Darrell B. O'Quinn,et al.  Emergence of the Th17 pathway and its role in host defense. , 2008, Advances in immunology.

[49]  R. D. Hatton,et al.  Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages , 2005, Nature Immunology.

[50]  H. Hammad,et al.  Mechanism of action of clinically approved adjuvants. , 2009, Current opinion in immunology.

[51]  J. Cyster,et al.  Germinal-center organization and cellular dynamics. , 2007, Immunity.

[52]  David A Johnson,et al.  Synthetic TLR4-active glycolipids as vaccine adjuvants and stand-alone immunotherapeutics. , 2008, Current topics in medicinal chemistry.

[53]  Hidde L. Ploegh,et al.  Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions , 2006, Advances in Immunology.

[54]  K. P. Murphy,et al.  Janeway's immunobiology , 2007 .

[55]  R. Coffman,et al.  Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. , 1986, Journal of immunology.

[56]  C. Hsieh,et al.  Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. , 1993, Science.

[57]  F. Sallusto,et al.  Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha , 1994, The Journal of experimental medicine.

[58]  T. Nomura,et al.  Regulatory T Cells and Immune Tolerance , 2008, Cell.

[59]  Katherine A. Fitzgerald,et al.  Superior Immunogenicity of Inactivated Whole Virus H5N1 Influenza Vaccine is Primarily Controlled by Toll-like Receptor Signalling , 2008, PLoS pathogens.

[60]  C. Janeway.  Approaching the asymptote? Evolution and revolution in immunology. , 1989, Cold Spring Harbor symposia on quantitative biology.

[61]  R. Alon,et al.  Immune cell migration in inflammation: present and future therapeutic targets , 2005, Nature Immunology.

[62]  H. Ochs,et al.  The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3 , 2001, Nature Genetics.

[63]  Mark M. Davis,et al.  Isolation of cDNA clones encoding T cell-specific membrane-associated proteins , 1984, Nature.

[64]  C. Baty,et al.  Noncytotoxic Lytic Granule–Mediated CD8+ T Cell Inhibition of HSV-1 Reactivation from Neuronal Latency , 2008, Science.

[65]  F. Finkelman,et al.  Interleukin‐4‐ and interleukin‐13‐mediated host protection against intestinal nematode parasites , 2004, Immunological reviews.

[66]  Tak W. Mak,et al.  A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains , 1984, Nature.

[67]  N. Maizels,et al.  The T-cell-independent immune response to the hapten NP uses a large repertoire of heavy chain genes , 1985, Cell.

[68]  H. Weiner,et al.  Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells , 2006, Nature.

[69]  N. Fazilleau,et al.  Local development of effector and memory T helper cells. , 2007, Current opinion in immunology.

[70]  A. Goldberg,et al.  Protein degradation and the generation of MHC class I-presented peptides. , 2002, Advances in immunology.

[71]  R. Locksley,et al.  Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets , 1989, The Journal of experimental medicine.

[72]  James E. Crowe,et al.  Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors , 2008, Nature.

[73]  M. Bevan,et al.  Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help , 2003, Science.

[74]  Susumu Tonegawa,et al.  A complete immunoglobulin gene is created by somatic recombination , 1978, Cell.

[75]  F. Martinon,et al.  The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. , 2002, Molecular cell.

[76]  S. Sakaguchi.  Regulatory T cells: mediating compromises between host and parasite , 2003, Nature Immunology.

[77]  M. Bachmann,et al.  Chemokines: more than just road signs , 2006, Nature Reviews Immunology.