Skip to main content

Overview of the Immune System and Its Pharmacological Targets

  • Chapter
  • First Online:
Pharmacology of Immunotherapeutic Drugs

Abstract

The immune system plays a vital role in maintaining the balance between health and disease. Immune cells provide protection against various pathogenic organisms, protecting the host from infection and injury to health. This protection is essential for the survival of the host and contributes to the overall health and longevity of individuals. In contrast, dysregulation of the immune system, resulting in overactive immune responses or autoimmunity are detrimental to the host, and induce tissue damage and development of disease. Chronic inflammation is associated with a number of diseases such as allergy, asthma, inflammatory bowel disease, rheumatoid arthritis, and cancer. This chapter will provide a general overview of the immune system and the principles of the innate and adaptive immune responses. The various cells and molecules of the innate and adaptive immune systems will be discussed and their role in immunity will be examined. In the second half of the chapter, we will examine pharmacological approaches to treating inflammation, and will discuss the various classes of drugs that target immune cells and their mediators. These include drugs that cause immunosuppression, those that prevent the proliferation of immune cells, and those that modulate immune activity. The suggested reading list at the end of the chapter highlights major discoveries in the field of immunology during the last two centuries that have advanced our current understanding of immunology and medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    The suggested reading list below was created with the aim of highlighting classic papers in immunology that describe seminal findings in the field of immunology. Many of these discoveries have advanced our current understanding of immunology and medicine and several have resulted in the receipt of the Nobel Prize.

Suggested Reading

The suggested reading list below was created with the aim of highlighting classic papers in immunology that describe seminal findings in the field of immunology. Many of these discoveries have advanced our current understanding of immunology and medicine and several have resulted in the receipt of the Nobel Prize.

  • Jenner E. An inquiry into the causes and effects of variolae vaccinae: a disease discovered in some Western Counties of England. London: Sampson Low; 1798. p. 75.

    Google Scholar 

  • Jenner E. Letter addressed to the medical profession generally, relative to vaccination. Lond Med Phys J. 1821;45:277–80.

    PubMed  PubMed Central  Google Scholar 

  • Pasteur L. Sur les maladies virulentes, et en particulier sur la maladie appelee vulgairement cholera des poules. C R Acad Sci. 1880;90:248–9.

    Google Scholar 

  • Pasteur LC, Roux E. Compte rendu sommaire des experiences faites a Pouilly-Le-Fort, pres de Melun, sur la vaccination charnonneuse. C R Acad Sci. 1881;92:1378–83.

    Google Scholar 

  • Koch R. A further communication on a remedy for tuberculosis. Br Med J. 1891;1:125–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koch R. An address on the fight against tuberculosis in the light of the experience that has been gained in the successful combat of other infectious diseases. Br Med J. 1901;2:189–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weil R. Studies in anaphylaxis. XIV. On the relation between precipitin and sensitizin. J Immunol. 1916;1:1–18.

    CAS  Google Scholar 

  • Lurie MB. A correlation between the histological changes and the fate of living tubercule bacilli in the organs of infected rabbits. J Exp Med. 1933;57:31–54.

    Article  Google Scholar 

  • Gibson T, Medawar PB. The fate of skin homografts in man. J Anat. 1943;77:299–310 294.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chase MW. The cellular transfer of cutaneous sensitivity to tuberculin. Proc Soc Exp Biol Med. 1945;59:134.

    Article  Google Scholar 

  • Coombs RR, Mourant AE, Race RR. A new test for the detection of weak and incomplete Rh agglutinins. Br J Exp Pathol. 1945;26:255–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins. Science. 1945;102:400–1.

    Article  CAS  PubMed  Google Scholar 

  • Fagraeus A. Plasma cellular reaction and its relation to the formation of antibodies in vitro. Nature. 1947;159:499.

    Article  CAS  PubMed  Google Scholar 

  • Fagraeus A. The plasma cellular reaction and its relation to the formation of antibodies in vitro. J Immunol. 1948;58:1–13.

    CAS  PubMed  Google Scholar 

  • Snell GD. Methods for the study of histocompatibility genes. J Genet. 1948;49:87–108.

    Article  CAS  PubMed  Google Scholar 

  • Bordley JE, Carey RA, et al. Preliminary observations on the effect of adrenocorticotropic hormone in allergic diseases. Bull Johns Hopkins Hosp. 1949;85:396–8.

    CAS  PubMed  Google Scholar 

  • Hench PS, Kendall EC, Slocumb CH, Polley HF. Effects of cortisone acetate and pituitary ACTH on rheumatoid arthritis, rheumatic fever and certain other conditions. Arch Intern Med (Chic). 1950;85:545–666.

    Article  CAS  Google Scholar 

  • Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature. 1953;172:603–6.

    Article  CAS  PubMed  Google Scholar 

  • Jerne NK. The natural-selection theory of antibody formation. Proc Natl Acad Sci U S A. 1955;41:849–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Billingham RE, Brent L, Medawar PB. The antigenic stimulus in transplantation immunity. Nature. 1956;178:514–9.

    Article  CAS  PubMed  Google Scholar 

  • Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147:258–67.

    Article  CAS  PubMed  Google Scholar 

  • Isaacs A, Lindenmann J, Valentine RC. Virus interference. II. Some properties of interferon. Proc R Soc Lond B Biol Sci. 1957;147:268–73.

    Article  CAS  PubMed  Google Scholar 

  • Nossal GJ, Lederberg J. Antibody production by single cells. Nature. 1958;181:1419–20.

    Article  CAS  PubMed  Google Scholar 

  • Porter RR. Separation and isolation of fractions of rabbit gamma-globulin containing the antibody and antigenic combining sites. Nature. 1958;182:670–1.

    Article  CAS  PubMed  Google Scholar 

  • Burnet FM. The clonal selection theory of acquired immunity. Cambridge: Cambridge University Press; 1959.

    Book  Google Scholar 

  • Nowell PC. Phytohemagglutinin: an initiator of mitosis in cultures of normal human leukocytes. Cancer Res. 1960;20:462–6.

    CAS  PubMed  Google Scholar 

  • Yalow RS, Berson SA. Immunoassay of endogenous plasma insulin in man. J Clin Invest. 1960;39:1157–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dresser DW. Effectiveness of lipid and lipidophilic substances as adjuvants. Nature. 1961;191:1169–71.

    Article  CAS  PubMed  Google Scholar 

  • Burnet FM. The immunological significance of the thymus: an extension of the clonal selection theory of immunity. Australas Ann Med. 1962;11:79–91.

    Article  CAS  PubMed  Google Scholar 

  • Dresser DW. Specific inhibition of antibody production. II. Paralysis induced in adult mice by small quantities of protein antigen. Immunology. 1962;5:378–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mackaness GB. Cellular resistance to infection. J Exp Med. 1962;116:381–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mackaness GB. The immunological basis of acquired cellular resistance. J Exp Med. 1964;120:105–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cooper MD, Peterson RD, Good RA. Delineation of the thymic and bursal lymphoid systems in the chicken. Nature. 1965;205:143–6.

    Article  CAS  PubMed  Google Scholar 

  • Brenner S, Milstein C. Origin of antibody variation. Nature. 1966;211:242–3.

    Article  CAS  PubMed  Google Scholar 

  • Cooper MD, Raymond DA, Peterson RD, South MA, Good RA. The functions of the thymus system and the bursa system in the chicken. J Exp Med. 1966;123:75–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishizaka K, Ishizaka T. Physicochemical properties of reaginic antibody. 1. Association of reaginic activity with an immunoglobulin other than gammaA- or gammaG-globulin. J Allergy. 1966a;37:169–85.

    Article  CAS  PubMed  Google Scholar 

  • Ishizaka K, Ishizaka T. Physicochemical properties of reaginic antibody. 3. Further studies on the reaginic antibody in gamma-A-globulin preparations. J Allergy. 1966b;38:108–19.

    Article  CAS  PubMed  Google Scholar 

  • Ishizaka K, Ishizaka T, Lee EH. Physiochemical properties of reaginic antibody. II. Characteristic properties of reaginic antibody different from human gamma-A-isohemagglutinin and gamma-D-globulin. J Allergy. 1966a;37:336–49.

    Article  CAS  PubMed  Google Scholar 

  • Ishizaka K, Ishizaka T, Hornbrook MM. Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. J Immunol. 1966b;97:75–85.

    CAS  PubMed  Google Scholar 

  • Ishizaka K, Ishizaka T, Hornbrook MM. Physicochemical properties of reaginic antibody. V. Correlation of reaginic activity wth gamma-E-globulin antibody. J Immunol. 1966c;97:840–53.

    CAS  PubMed  Google Scholar 

  • Edelman GM, Gally JA. Somatic recombination of duplicated genes: an hypothesis on the origin of antibody diversity. Proc Natl Acad Sci U S A. 1967;57:353–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henney CS, Ishizaka K. An antigenic determinant of human gamma-globulin susceptible to papain digestion. J Immunol. 1967;99:695–702.

    CAS  PubMed  Google Scholar 

  • Ishizaka K, Ishizaka T. Identification of gamma-E-antibodies as a carrier of reaginic activity. J Immunol. 1967;99:1187–98.

    CAS  PubMed  Google Scholar 

  • Ishizaka K, Ishizaka T, Menzel AE. Physicochemical properties of reaginic antibody. VI. Effect of heat on gamma-E-, gamma-G- and gamma-A-antibodies in the sera of ragweed sensitive patients. J Immunol. 1967a;99:610–8.

    CAS  PubMed  Google Scholar 

  • Ishizaka K, Ishizaka T, Terry WD. Antigenic structure of gamma-E-globulin and reaginic antibody. J Immunol. 1967b;99:849–58.

    CAS  PubMed  Google Scholar 

  • Johansson SG, Bennich H. Immunological studies of an atypical (myeloma) immunoglobulin. Immunology. 1967;13:381–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mintz B, Silvers WK. “Intrinsic” immunological tolerance in allophenic mice. Science. 1967;158:1484–6.

    Article  CAS  PubMed  Google Scholar 

  • Mishell RI, Dutton RW. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967;126:423–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edelman GM, et al. The covalent structure of an entire gammaG immunoglobulin molecule. Proc Natl Acad Sci U S A. 1969;63:78–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klinman NR. Antibody with homogeneous antigen binding produced by splenic foci in organ culture. Immunochemistry. 1969;6:757–9.

    Article  CAS  PubMed  Google Scholar 

  • McDevitt HO, Chinitz A. Genetic control of the antibody response: relationship between immune response and histocompatibility (H-2) type. Science. 1969;163:1207–8.

    Article  CAS  PubMed  Google Scholar 

  • Raff MC. Two distinct populations of peripheral lymphocytes in mice distinguishable by immunofluorescence. Immunology. 1970;19:637–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu TT, Kabat EA. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med. 1970;132:211–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Armstrong JA, D’Arcy Hart P. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med. 1971;134:713–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craig SW, Cebra JJ. Peyer’s patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J Exp Med. 1971;134:188–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cudkowicz G, Bennett M. Peculiar immunobiology of bone marrow allografts. I. Graft rejection by irradiated responder mice. J Exp Med. 1971a;134:83–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cudkowicz G, Bennett M. Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by resistant F 1 hybrid mice. J Exp Med. 1971b;134:1513–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry. 1971;8:871–4.

    Article  CAS  PubMed  Google Scholar 

  • Jerne NK. The somatic generation of immune recognition. Eur J Immunol. 1971;1:1–9.

    Article  CAS  PubMed  Google Scholar 

  • Mitchison NA. The carrier effect in the secondary response to hapten-protein conjugates. I. Measurement of the effect with transferred cells and objections to the local environment hypothesis. Eur J Immunol. 1971a;1:10–7.

    Article  CAS  PubMed  Google Scholar 

  • Mitchison NA. The carrier effect in the secondary response to hapten-protein conjugates. II. Cellular cooperation. Eur J Immunol. 1971b;1:18–27.

    Article  CAS  PubMed  Google Scholar 

  • Sprent J, Miller JF, Mitchell GF. Antigen-induced selective recruitment of circulating lymphocytes. Cell Immunol. 1971;2:171–81.

    Article  CAS  PubMed  Google Scholar 

  • Klinman NR. The mechanism of antigenic stimulation of primary and secondary clonal precursor cells. J Exp Med. 1972;136:241–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Babior BM, Kipnes RS, Curnutte JT. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973;52:741–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cotton RG, Milstein C. Letter: fusion of two immunoglobulin-producing myeloma cells. Nature. 1973;244:42–3.

    Article  CAS  PubMed  Google Scholar 

  • Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 1973;137:1142–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strander H, Cantell K, Carlstrom G, Jakobsson PA. Clinical and laboratory investigations on man: systemic administration of potent interferon to man. J Natl Cancer Inst. 1973;51:733–42.

    Article  CAS  PubMed  Google Scholar 

  • Bottazzo GF, Florin-Christensen A, Doniach D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet. 1974;2:1279–83.

    Article  CAS  PubMed  Google Scholar 

  • Brandtzaeg P. Mucosal and glandular distribution of immunoglobulin components: differential localization of free and bound SC in secretory epithelial cells. J Immunol. 1974;112:1553–9.

    CAS  PubMed  Google Scholar 

  • MacCuish AC, Irvine WJ, Barnes EW, Duncan LJ. Antibodies to pancreatic islet cells in insulin-dependent diabetics with coexistent autoimmune disease. Lancet. 1974;2:1529–31.

    Article  CAS  PubMed  Google Scholar 

  • Owen JJ, Cooper MD, Raff MC. In vitro generation of B lymphocytes in mouse foetal liver, a mammalian ‘bursa equivalent’. Nature. 1974;249:361–3.

    Article  CAS  PubMed  Google Scholar 

  • Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med. 1974;139:380–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zinkernagel RM, Doherty PC. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974;248:701–2.

    Article  CAS  PubMed  Google Scholar 

  • Bevan MJ. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J Exp Med. 1975;142:1349–64.

    Article  CAS  PubMed  Google Scholar 

  • Cantor H, Boyse EA. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975a;141:1376–89.

    Article  CAS  PubMed  Google Scholar 

  • Cantor H, Boyse EA. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975b;141:1390–9.

    Article  CAS  PubMed  Google Scholar 

  • Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–7.

    Article  CAS  PubMed  Google Scholar 

  • Burnet FM. A modification of Jerne’s theory of antibody production using the concept of clonal selection. CA Cancer J Clin. 1976;26:119–21.

    Article  CAS  PubMed  Google Scholar 

  • Hozumi N, Tonegawa S. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc Natl Acad Sci U S A. 1976;73:3628–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solley GO, Gleich GJ, Jordon RE, Schroeter AL. The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies. J Clin Invest. 1976;58:408–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robinson JH, Owen JJ. Generation of T-cell function in organ culture of foetal mouse thymus. II. Mixed lymphocyte culture reactivity. Clin Exp Immunol. 1977;27:322–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ruscetti FW, Morgan DA, Gallo RC. Functional and morphologic characterization of human T cells continuously grown in vitro. J Immunol. 1977;119:131–8.

    CAS  PubMed  Google Scholar 

  • Silverton EW, Navia MA, Davies DR. Three-dimensional structure of an intact human immunoglobulin. Proc Natl Acad Sci U S A. 1977;74:5140–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brack C, Hirama M, Lenhard-Schuller R, Tonegawa S. A complete immunoglobulin gene is created by somatic recombination. Cell. 1978;15:1–14.

    Article  CAS  PubMed  Google Scholar 

  • Baker PE, Gillis S, Smith KA. Monoclonal cytolytic T-cell lines. J Exp Med. 1979;149:273–8.

    Article  CAS  PubMed  Google Scholar 

  • Kung P, Goldstein G, Reinherz EL, Schlossman SF. Monoclonal antibodies defining distinctive human T cell surface antigens. Science. 1979;206:347–9.

    Article  CAS  PubMed  Google Scholar 

  • Murphy RC, Hammarstrom S, Samuelsson B. Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci U S A. 1979;76:4275–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parks DR, Bryan VM, Oi VT, Herzenberg LA. Antigen-specific identification and cloning of hybridomas with a fluorescence-activated cell sorter. Proc Natl Acad Sci U S A. 1979;76:1962–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reinherz EL, Kung PC, Goldstein G, Schlossman SF. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979;76:4061–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silverstein AM. History of immunology. Cell Immunol. 1979a;42:1–2.

    Article  CAS  PubMed  Google Scholar 

  • Silverstein AM. History of immunology. Cellular versus humoral immunity: determinants and consequences of an epic 19th century battle. Cell Immunol. 1979b;48:208–21.

    Article  CAS  PubMed  Google Scholar 

  • Davis MM, et al. An immunoglobulin heavy-chain gene is formed by at least two recombinational events. Nature. 1980;283:733–9.

    Article  CAS  PubMed  Google Scholar 

  • Early P, Huang H, Davis M, Calame K, Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980;19:981–92.

    Article  CAS  PubMed  Google Scholar 

  • Silverstein AM, Bialasiewicz AA. History of immunology. A history of theories of acquired immunity. Cell Immunol. 1980;51:151–67.

    Article  CAS  PubMed  Google Scholar 

  • Van Wauwe JP, De Mey JR, Goossens JG. OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J Immunol. 1980;124:2708–13.

    PubMed  Google Scholar 

  • Kappler JW, Skidmore B, White J, Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981;153:1198–214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silverstein AM, Miller G. History of immunology. The royal experiment on immunity: 1721-1722. Cell Immunol. 1981;61:437–47.

    Article  CAS  PubMed  Google Scholar 

  • Steiner H, Hultmark D, Engstrom A, Bennich H, Boman HG. Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature. 1981;292:246–8.

    Article  CAS  PubMed  Google Scholar 

  • Ziegler K, Unanue ER. Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes. J Immunol. 1981;127:1869–75.

    CAS  PubMed  Google Scholar 

  • Allison JP, McIntyre BW, Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol. 1982;129:2293–300.

    CAS  PubMed  Google Scholar 

  • Butcher EC, et al. Surface phenotype of Peyer’s patch germinal center cells: implications for the role of germinal centers in B cell differentiation. J Immunol. 1982;129:2698–707.

    CAS  PubMed  Google Scholar 

  • Howard M, et al. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982;155:914–23.

    Article  CAS  PubMed  Google Scholar 

  • Isakson PC, Pure E, Vitetta ES, Krammer PH. T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. J Exp Med. 1982;155:734–48.

    Article  CAS  PubMed  Google Scholar 

  • Silverstein AM. History of immunology. Development of the concept of immunologic specificity, I. Cell Immunol. 1982a;67:396–409.

    Article  CAS  PubMed  Google Scholar 

  • Silverstein AM. History of immunology: development of the concept of immunologic specificity: II. Cell Immunol. 1982b;71:183–95.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi N, et al. Structure of human immunoglobulin gamma genes: implications for evolution of a gene family. Cell. 1982;29:671–9.

    Article  CAS  PubMed  Google Scholar 

  • Turkeltaub PC, Rastogi SC, Baer H, Anderson MC, Norman PS. A standardized quantitative skin-test assay of allergen potency and stability: studies on the allergen dose-response curve and effect of wheal, erythema, and patient selection on assay results. J Allergy Clin Immunol. 1982;70:343–52.

    Article  CAS  PubMed  Google Scholar 

  • Haskins K, et al. The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med. 1983;157:1149–69.

    Article  CAS  PubMed  Google Scholar 

  • Kappler J, et al. The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man: identification of constant and variable peptides. Cell. 1983;35:295–302.

    Article  CAS  PubMed  Google Scholar 

  • Tonegawa S. Somatic generation of antibody diversity. Nature. 1983;302:575–81.

    Article  CAS  PubMed  Google Scholar 

  • Auron PE, et al. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984;81:7907–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gough NM, et al. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. Nature. 1984;309:763–7.

    Article  CAS  PubMed  Google Scholar 

  • Hedrick SM, Cohen DI, Nielsen EA, Davis MM. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984;308:149–53.

    Article  CAS  PubMed  Google Scholar 

  • Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311–5.

    Article  CAS  PubMed  Google Scholar 

  • McKean D, et al. Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1984;81:3180–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrison SL, Johnson MJ, Herzenberg LA, Oi VT. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A. 1984;81:6851–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rock KL, Benacerraf B, Abbas AK. Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. J Exp Med. 1984;160:1102–13.

    Article  CAS  PubMed  Google Scholar 

  • Townsend AR, McMichael AJ, Carter NP, Huddleston JA, Brownlee GG. Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell. 1984;39:13–25.

    Article  CAS  PubMed  Google Scholar 

  • Babbitt BP, Allen PM, Matsueda G, Haber E, Unanue ER. Binding of immunogenic peptides to Ia histocompatibility molecules. Nature. 1985;317:359–61.

    Article  CAS  PubMed  Google Scholar 

  • Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985;229:869–71.

    Article  CAS  PubMed  Google Scholar 

  • Jenner E, Pasteur L. [From Jenner to Pasteur or the development of ideas on vaccination]. Bull Acad Natl Med. 1985;169:771–8.

    Google Scholar 

  • Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985;314:537–9.

    Article  CAS  PubMed  Google Scholar 

  • Nakano T, et al. Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells. J Exp Med. 1985;162:1025–43.

    Article  CAS  PubMed  Google Scholar 

  • Brenner MB, et al. Identification of a putative second T-cell receptor. Nature. 1986;322:145–9.

    Article  CAS  PubMed  Google Scholar 

  • Clark EA, Ledbetter JA. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A. 1986;83:4494–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986;137:245–54.

    CAS  PubMed  Google Scholar 

  • Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature. 1986;321:522–5.

    Article  CAS  PubMed  Google Scholar 

  • Karre K, Ljunggren HG, Piontek G, Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986;319:675–8.

    Article  CAS  PubMed  Google Scholar 

  • Kehrl JH, et al. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986;163:1037–50.

    Article  CAS  PubMed  Google Scholar 

  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348–57.

    CAS  PubMed  Google Scholar 

  • Rothlein R, Dustin ML, Marlin SD, Springer TA. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986;137:1270–4.

    CAS  PubMed  Google Scholar 

  • Royer-Pokora B, et al. Cloning the gene for an inherited human disorder—chronic granulomatous disease—on the basis of its chromosomal location. Nature. 1986;322:32–8.

    Article  CAS  PubMed  Google Scholar 

  • Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986a;47:921–8.

    Article  CAS  PubMed  Google Scholar 

  • Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986b;46:705–16.

    Article  CAS  PubMed  Google Scholar 

  • Bjorkman PJ, et al. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987a;329:506–12.

    Article  CAS  PubMed  Google Scholar 

  • Bjorkman PJ, et al. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987b;329:512–8.

    Article  CAS  PubMed  Google Scholar 

  • Brunet JF, et al. A new member of the immunoglobulin superfamily—CTLA-4. Nature. 1987;328:267–70.

    Article  CAS  PubMed  Google Scholar 

  • Cher DJ, Mosmann TR. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol. 1987;138:3688–94.

    CAS  PubMed  Google Scholar 

  • Doyle C, Strominger JL. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987;330:256–9.

    Article  CAS  PubMed  Google Scholar 

  • Jenkins MK, Schwartz RH. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med. 1987;165:302–19.

    Article  CAS  PubMed  Google Scholar 

  • Kappler JW, Roehm N, Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987;49:273–80.

    Article  CAS  PubMed  Google Scholar 

  • Orme IM. The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis. J Immunol. 1987;138:293–8.

    CAS  PubMed  Google Scholar 

  • Snapper CM, Paul WE. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987;236:944–7.

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura T, Matsushima K, Oppenheim JJ, Leonard EJ. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol. 1987a;139:788–93.

    CAS  PubMed  Google Scholar 

  • Yoshimura T, et al. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A. 1987b;84:9233–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bird RE, et al. Single-chain antigen-binding proteins. Science. 1988;242:423–6.

    Article  CAS  PubMed  Google Scholar 

  • Goodnow CC, et al. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature. 1988;334:676–82.

    Article  CAS  PubMed  Google Scholar 

  • Schall TJ, et al. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988;141:1018–25.

    CAS  PubMed  Google Scholar 

  • Shaw JP, et al. Identification of a putative regulator of early T cell activation genes. Science. 1988;241:202–5.

    Article  CAS  PubMed  Google Scholar 

  • Coffman RL, Lebman DA, Shrader B. Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. J Exp Med. 1989;170:1039–44.

    Article  CAS  PubMed  Google Scholar 

  • Emmel EA, et al. Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science. 1989;246:1617–20.

    Article  CAS  PubMed  Google Scholar 

  • Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170:2081–95.

    Article  CAS  PubMed  Google Scholar 

  • Janeway CA Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):1–13.

    Article  CAS  PubMed  Google Scholar 

  • Lefrancois L, Goodman T. In vivo modulation of cytolytic activity and Thy-1 expression in TCR-gamma delta+ intraepithelial lymphocytes. Science. 1989;243:1716–8.

    Article  CAS  PubMed  Google Scholar 

  • Porcelli S, et al. Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes. Nature. 1989;341:447–50.

    Article  CAS  PubMed  Google Scholar 

  • Schatz DG, Oettinger MA, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell. 1989;59:1035–48.

    Article  CAS  PubMed  Google Scholar 

  • Sonoda E, et al. Transforming growth factor beta induces IgA production and acts additively with interleukin 5 for IgA production. J Exp Med. 1989;170:1415–20.

    Article  CAS  PubMed  Google Scholar 

  • Townsend A, et al. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature. 1989;340:443–8.

    Article  CAS  PubMed  Google Scholar 

  • Wright AE, Douglas SR, Sanderson JB. An experimental investigation of the role of the blood fluids in connection with phagocytosis. 1903. Rev Infect Dis. 1989;11:827–34.

    Article  CAS  PubMed  Google Scholar 

  • Conrad DH, Ben-Sasson SZ, Le Gros G, Finkelman FD, Paul WE. Infection with Nippostrongylus brasiliensis or injection of anti-IgD antibodies markedly enhances Fc-receptor-mediated interleukin 4 production by non-B, non-T cells. J Exp Med. 1990;171:1497–508.

    Article  CAS  PubMed  Google Scholar 

  • Hombach J, Tsubata T, Leclercq L, Stappert H, Reth M. Molecular components of the B-cell antigen receptor complex of the IgM class. Nature. 1990;343:760–2.

    Article  CAS  PubMed  Google Scholar 

  • Koller BH, Marrack P, Kappler JW, Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990;248:1227–30.

    Article  CAS  PubMed  Google Scholar 

  • Le Gros G, Ben-Sasson SZ, Seder R, Finkelman FD, Paul WE. Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med. 1990;172:921–9.

    Article  PubMed  Google Scholar 

  • Linsley PS, Clark EA, Ledbetter JA. T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. Proc Natl Acad Sci U S A. 1990;87:5031–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monaco JJ, Cho S, Attaya M. Transport protein genes in the murine MHC: possible implications for antigen processing. Science. 1990;250:1723–6.

    Article  CAS  PubMed  Google Scholar 

  • Moore KW, et al. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990;248:1230–4.

    Article  CAS  PubMed  Google Scholar 

  • Oettinger MA, Schatz DG, Gorka C, Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990;248:1517–23.

    Article  CAS  PubMed  Google Scholar 

  • Ruddle NH, et al. An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med. 1990;172:1193–200.

    Article  CAS  PubMed  Google Scholar 

  • Zijlstra M, et al. Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T cells. Nature. 1990;344:742–6.

    Article  CAS  PubMed  Google Scholar 

  • Falk K, Rotzschke O, Stevanovic S, Jung G, Rammensee HG. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991;351:290–6.

    Article  CAS  PubMed  Google Scholar 

  • Fiorentino DF, et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991;146:3444–51.

    CAS  PubMed  Google Scholar 

  • Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI. Structure and functional expression of a human interleukin-8 receptor. Science. 1991;253:1278–80.

    Article  CAS  PubMed  Google Scholar 

  • Murphy PM, Tiffany HL. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science. 1991;253:1280–3.

    Article  CAS  PubMed  Google Scholar 

  • Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med. 1991;173:159–66.

    Article  CAS  PubMed  Google Scholar 

  • Rudensky A, Preston-Hurlburt P, Hong SC, Barlow A, Janeway CA Jr. Sequence analysis of peptides bound to MHC class II molecules. Nature. 1991;353:622–7.

    Article  CAS  PubMed  Google Scholar 

  • Todd JA, et al. Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature. 1991;351:542–7.

    Article  CAS  PubMed  Google Scholar 

  • von Behring E, Kitasato S. [The mechanism of diphtheria immunity and tetanus immunity in animals. 1890]. Mol Immunol. 1991;28(1317):1319–20.

    Google Scholar 

  • Carter RH, Fearon DT. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science. 1992;256:105–7.

    Article  CAS  PubMed  Google Scholar 

  • Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11:3887–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janeway CA Jr. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today. 1992;13:11–6.

    Article  CAS  PubMed  Google Scholar 

  • Karlhofer FM, Ribaudo RK, Yokoyama WM. MHC class I alloantigen specificity of Ly-49+ IL-2-activated natural killer cells. Nature. 1992;358:66–70.

    Article  CAS  PubMed  Google Scholar 

  • Noelle RJ, et al. A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. Proc Natl Acad Sci U S A. 1992;89:6550–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schindler C, Shuai K, Prezioso VR, Darnell JE Jr. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science. 1992;257:809–13.

    Article  CAS  PubMed  Google Scholar 

  • Velazquez L, Fellous M, Stark GR, Pellegrini S. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. 1992;70:313–22.

    Article  CAS  PubMed  Google Scholar 

  • Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356:314–7.

    Article  CAS  PubMed  Google Scholar 

  • Zychlinsky A, Prevost MC, Sansonetti PJ. Shigella flexneri induces apoptosis in infected macrophages. Nature. 1992;358:167–9.

    Article  CAS  PubMed  Google Scholar 

  • Brown JH, et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature. 1993;364:33–9.

    Article  CAS  PubMed  Google Scholar 

  • Gay D, Saunders T, Camper S, Weigert M. Receptor editing: an approach by autoreactive B cells to escape tolerance. J Exp Med. 1993;177:999–1008.

    Article  CAS  PubMed  Google Scholar 

  • Heinzel FP, Rerko RM, Hatam F, Locksley RM. IL-2 is necessary for the progression of leishmaniasis in susceptible murine hosts. J Immunol. 1993;150:3924–31.

    CAS  PubMed  Google Scholar 

  • Hsieh CS, et al. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993;260:547–9.

    Article  CAS  PubMed  Google Scholar 

  • Noguchi M, et al. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993;73:147–57.

    Article  CAS  PubMed  Google Scholar 

  • Shinkai Y, et al. Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes. Science. 1993;259:822–5.

    Article  CAS  PubMed  Google Scholar 

  • Tiegs SL, Russell DM, Nemazee D. Receptor editing in self-reactive bone marrow B cells. J Exp Med. 1993;177:1009–20.

    Article  CAS  PubMed  Google Scholar 

  • De Togni P, et al. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994;264:703–7.

    Article  PubMed  Google Scholar 

  • Hogquist KA, et al. T cell receptor antagonist peptides induce positive selection. Cell. 1994;76:17–27.

    Article  CAS  PubMed  Google Scholar 

  • Iwashima M, Irving BA, van Oers NS, Chan AC, Weiss A. Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. Science. 1994;263:1136–9.

    Article  CAS  PubMed  Google Scholar 

  • Jardetzky TS, et al. Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen. Nature. 1994;368:711–8.

    Article  CAS  PubMed  Google Scholar 

  • Lau LL, Jamieson BD, Somasundaram T, Ahmed R. Cytotoxic T-cell memory without antigen. Nature. 1994;369:648–52.

    Article  CAS  PubMed  Google Scholar 

  • Saint-Ruf C, et al. Analysis and expression of a cloned pre-T cell receptor gene. Science. 1994;266:1208–12.

    Article  CAS  PubMed  Google Scholar 

  • Sallusto F, Lanzavecchia A. 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. J Exp Med. 1994;179:1109–18.

    Article  CAS  PubMed  Google Scholar 

  • Surh CD, Sprent J. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature. 1994;372:100–3.

    Article  CAS  PubMed  Google Scholar 

  • Walunas TL, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1:405–13.

    Article  CAS  PubMed  Google Scholar 

  • Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182:459–65.

    Article  CAS  PubMed  Google Scholar 

  • McBlane JF, et al. Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell. 1995;83:387–95.

    Article  CAS  PubMed  Google Scholar 

  • Robey E, Allison JP. T-cell activation: integration of signals from the antigen receptor and costimulatory molecules. Immunol Today. 1995;16:306–10.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. 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. J Immunol. 1995;155:1151–64.

    CAS  PubMed  Google Scholar 

  • Yao Z, et al. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity. 1995;3:811–21.

    Article  CAS  PubMed  Google Scholar 

  • Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996;272:872–7.

    Article  CAS  PubMed  Google Scholar 

  • Garboczi DN, et al. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature. 1996;384:134–41.

    Article  CAS  PubMed  Google Scholar 

  • Garcia KC, et al. An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science. 1996;274:209–19.

    Article  CAS  PubMed  Google Scholar 

  • Larsen CP, et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature. 1996;381:434–8.

    Article  CAS  PubMed  Google Scholar 

  • Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86:973–83.

    Article  CAS  PubMed  Google Scholar 

  • Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388:394–7.

    Article  CAS  PubMed  Google Scholar 

  • Muzio M, Ni J, Feng P, Dixit VM. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science. 1997;278:1612–5.

    Article  CAS  PubMed  Google Scholar 

  • Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao Z. MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity. 1997;7:837–47.

    Article  CAS  PubMed  Google Scholar 

  • Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997;89:587–96.

    Article  CAS  PubMed  Google Scholar 

  • Butz EA, Bevan MJ. Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity. 1998;8:167–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature. 1998;395:82–6.

    Article  CAS  PubMed  Google Scholar 

  • Murali-Krishna K, et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity. 1998;8:177–87.

    Article  CAS  PubMed  Google Scholar 

  • Poltorak A, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 1998;282:2085–8.

    Article  CAS  PubMed  Google Scholar 

  • Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998;101:273–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bauer S, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999;285:727–9.

    Article  CAS  PubMed  Google Scholar 

  • Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–9.

    Article  CAS  PubMed  Google Scholar 

  • Forster R, et al. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell. 1999;99:23–33.

    Article  CAS  PubMed  Google Scholar 

  • Grakoui A, et al. The immunological synapse: a molecular machine controlling T cell activation. Science. 1999;285:221–7.

    Article  CAS  PubMed  Google Scholar 

  • Hoshino K, et al. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol. 1999;162:3749–52.

    CAS  PubMed  Google Scholar 

  • Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11:141–51.

    Article  CAS  PubMed  Google Scholar 

  • Nutt SL, Heavey B, Rolink AG, Busslinger M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature. 1999;401:556–62.

    Article  CAS  PubMed  Google Scholar 

  • Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401:708–12.

    Article  CAS  PubMed  Google Scholar 

  • Muramatsu M, et al. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000;102:553–63.

    Article  CAS  PubMed  Google Scholar 

  • Szabo SJ, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100:655–69.

    Article  CAS  PubMed  Google Scholar 

  • Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565–94.

    Article  CAS  PubMed  Google Scholar 

  • Girardi M, et al. Regulation of cutaneous malignancy by gammadelta T cells. Science. 2001;294:605–9.

    Article  CAS  PubMed  Google Scholar 

  • Masopust D, Vezys V, Marzo AL, Lefrancois L. Preferential localization of effector memory cells in nonlymphoid tissue. Science. 2001;291:2413–7.

    Article  CAS  PubMed  Google Scholar 

  • Shankaran V, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410:1107–11.

    Article  CAS  PubMed  Google Scholar 

  • Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL. Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science. 2002;296:1323–6.

    Article  CAS  PubMed  Google Scholar 

  • Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4:330–6.

    Article  CAS  PubMed  Google Scholar 

  • Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–61.

    Article  CAS  PubMed  Google Scholar 

  • Pentcheva-Hoang T, Egen JG, Wojnoonski K, Allison JP. B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity. 2004;21:401–13.

    Article  CAS  PubMed  Google Scholar 

  • Silverstein AM. Paul Ehrlich, archives and the history of immunology. Nat Immunol. 2005;6:639.

    Article  CAS  PubMed  Google Scholar 

  • Khanna KM, McNamara JT, Lefrancois L. In situ imaging of the endogenous CD8 T cell response to infection. Science. 2007;318:116–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaufmann SH. Immunology’s foundation: the 100-year anniversary of the Nobel Prize to Paul Ehrlich and Elie Metchnikoff. Nat Immunol. 2008a;9:705–12.

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann SH. Paul Ehrlich: founder of chemotherapy. Nat Rev Drug Discov. 2008b;7:373.

    Article  CAS  PubMed  Google Scholar 

  • Robinson JH, Owen JJ. Pillars article: generation of T-cell function in organ culture of foetal mouse thymus I. Mitogen responsiveness. 1975. J Immunol. 2008;181:7437–44.

    Article  CAS  PubMed  Google Scholar 

  • Xu Z, Zan H, Pone EJ, Mai T, Casali P. Immunoglobulin class-switch DNA recombination: induction, targeting and beyond. Nat Rev Immunol. 2012;12:517–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cooper MD. The early history of B cells. Nat Rev Immunol. 2015;15:191–7.

    Article  CAS  PubMed  Google Scholar 

  • Gitlin AD, Nussenzweig MC. Immunology: fifty years of B lymphocytes. Nature. 2015;517:139–41.

    Article  CAS  PubMed  Google Scholar 

  • Akdis M, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: receptors, functions, and roles in disease. J Allergy Clin Immunol. 2016;138:984–1010.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Clinton B. Mathias .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Mathias, C.B. (2020). Overview of the Immune System and Its Pharmacological Targets. In: Mathias, C., McAleer, J., Szollosi, D. (eds) Pharmacology of Immunotherapeutic Drugs. Springer, Cham. https://doi.org/10.1007/978-3-030-19922-7_1

Download citation

Publish with us

Policies and ethics