Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Some Basic Cellular Immunology Principles Applied to the Pathogenesis of Infectious Diseases

  • Chapter
Immunotherapy for Infectious Diseases

Part of the book series: Infectious Disease ((ID))

  • 143 Accesses

Abstract

In this chapter some of the functional implications of our current understanding of the basic physiology of T-cell mediated immune function for problems in infectious disease are discussed. The subtleties of the process of T-cell antigen “recognition” and the heterogeneity of kinds of functional responses within the T-cell system are a major focus. Finally, some features of the anatomic compartmentalization of the immune system and how limited access to tissue compartments skews our thinking about in vivo immunity in humans are explored. In view of our recently enhanced understanding of HIV disease, the chapter uses this viral infection as an example to illustrate relevant immune mechanisms and concepts.

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

Access this chapter

Log in via an institution
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 109.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. June CH, Ledbetter JA, Gillespie MM, Lindsten T, Thompson CB. T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol 1987; 7: 4472–4481.

    PubMed  CAS  Google Scholar 

  2. Thompson CB, Lindsten T, Ledbetter JA, et al. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci USA 1989; 86: 1333–1337.

    Article  PubMed  CAS  Google Scholar 

  3. Fraser JD, Irving, BA, Crabtree GR, Weiss A. Regulation of interleukin-2 gene enhancer activity by the T cell accessory molecule CD28. Science 1991; 251: 313–316.

    Article  PubMed  CAS  Google Scholar 

  4. Dustin ML, Springer TA. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 1989; 341: 619–624.

    Article  PubMed  CAS  Google Scholar 

  5. Bierer BE, Sleckman BP, Ratnofsky SE, Burakoff SJ. The biologic roles of CD2, CD4, and CD8 in T-cell activation. Ann Rev Immunol 1989; 7: 579.

    Article  CAS  Google Scholar 

  6. Pingel JT, Thomas ML. Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. Cell 1989; 58: 1055–1065.

    Article  PubMed  CAS  Google Scholar 

  7. Koretzky GA, Picus J, Thomas ML, Weiss A. Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway. Nature 1990; 346: 66–68.

    Article  PubMed  CAS  Google Scholar 

  8. Trowbridge IS, Thomas ML. CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Annu Rev Immunol 1994; 12: 85–116.

    Article  PubMed  CAS  Google Scholar 

  9. Kisielow P, Blüthmann H, Staerz UD, Steinmetz M, von Boehmer H. Tolerance in T cell receptor transgenic mice involves deletion of nonmature CD4 F8+ thymocytes. Nature 1988; 333: 742–746.

    Article  PubMed  CAS  Google Scholar 

  10. Kappler JW, Staerz U, White J, Marrack, P. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature 1988; 332: 35–40.

    Article  PubMed  CAS  Google Scholar 

  11. MacDonald HR, Lees RK, Schneider R, Zinkernagel RM, Hengartner H. Positive selection of CD4+ thymocytes controlled by MHC class II gene products. Nature 1988; 336: 471–473.

    Article  PubMed  CAS  Google Scholar 

  12. Tough DF, Sprent J. Turnover of naive and memory phenotype T cells. J Exp Med 1994; 179: 1127–1136.

    Article  PubMed  CAS  Google Scholar 

  13. Sprent J, Tough DF, Sun S. Factors controlling the turnover of T memory cells. Immunol Rev 1997; 156: 79–85.

    Article  PubMed  CAS  Google Scholar 

  14. Rocha B, Grandien A, Freitas AA. Anergy and exhaustion are independent mechanisms of peripheral T cell tolerance. J Exp Med 1995; 181: 993–1003.

    Article  PubMed  CAS  Google Scholar 

  15. Tanchot C, Rocha B. The peripheral T-cell repertoire: independent homeostatic regulation of virgin and activated CD8+ T cell pools. Eur J Immunol 1995; 25: 2127–2136.

    Article  PubMed  CAS  Google Scholar 

  16. Takeda S, Rodewald HR, Arakawa H, Bluethmann H, Shimizu T. MHC class II molecules are not required for survival of newly generated CD4+ T cells, but affect their long-term life span. Immunity 1996; 5: 217–228.

    Article  PubMed  CAS  Google Scholar 

  17. Brocker T. Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class II-expressing dendritic cells. J Exp Med 1997; 186: 1223–1232.

    Article  PubMed  CAS  Google Scholar 

  18. Kirberg J, Berns A, von Boehmer H. Peripheral T-cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules. J Exp Med 1997; 186: 1269–1275.

    Article  PubMed  CAS  Google Scholar 

  19. Metz DP, Farber DL, Konig R. Bottomly K. Regulation of memory CD4 T cell adhesion by CD4-MHC class II interaction. J Immunol 1997; 159: 2567–2573.

    PubMed  CAS  Google Scholar 

  20. Tanchot C, Rocha B. Peripheral selection of T cell repertoires: the role of continuous thymus output. J Exp Med 1997; 186: 1099–1106.

    Article  PubMed  CAS  Google Scholar 

  21. Buus S, Sette A, Colon SM, Miles C, Grey HM. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science 1987; 235: 1353–1358.

    Article  PubMed  CAS  Google Scholar 

  22. Schaeffer EB, Sette A, Johnson DL, et al. Relative contribution of “determinant selection” and “holes in the T-cell repertoire” to T-cell responses. Proc Natl Acad Sci USA 1989; 86: 4649–4653.

    Article  PubMed  CAS  Google Scholar 

  23. Kaslow RA, Carrington M, Apple R, et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 1996; 2: 405–411.

    Article  PubMed  CAS  Google Scholar 

  24. Saah, AJ, Hoover DR, Weng S, et al. Association of HLA profiles with early plasma viral load, CD4+ cell count and rate of progression to AIDS following acute HIV-1 infection. Multicenter AIDS Cohort Study. AIDS 1998; 12: 2107–2113.

    Article  PubMed  CAS  Google Scholar 

  25. Carrington M, Nelson GW, Martin MP, et al. HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 1999; 283: 1748–1752.

    Article  PubMed  CAS  Google Scholar 

  26. Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 1994; 68: 6103–6110.

    PubMed  CAS  Google Scholar 

  27. Klenerman P, Phillips RE, Rinaldo CR, et al. Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection. Proc Natl Acad Sci USA 1996; 93: 15323–15328.

    Article  PubMed  CAS  Google Scholar 

  28. Borrow P, Lewicki H, Wei X, et al. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 1997; 3: 205–211.

    Article  PubMed  CAS  Google Scholar 

  29. Ogg GS, Jin X, Bonhoeffer S, et al. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 1998; 279: 2103–2106.

    Article  PubMed  CAS  Google Scholar 

  30. Jin X, Bauer DE, Tuttleton SE, et al. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected Macaques. J Exp Med 1999; 189: 991–998.

    Article  PubMed  CAS  Google Scholar 

  31. Schmitz JE, Kuroda MJ, Santra S, et al. Control of viremia in simian immunodeficiency virus infection by CD8(+) lymphocytes. Science 1999; 283: 857–860.

    Article  PubMed  CAS  Google Scholar 

  32. McKeithan TW. Kinetic proofreading in T-cell receptor signal transduction. Proc Natl Acad Sci USA 1995; 92: 5042–5046.

    Article  PubMed  CAS  Google Scholar 

  33. Grakoui A, Bromley SK, Sumen C, et al. The immunological synapse: a molecular machine controlling T cell activation. Science 1999; 285: 221–227.

    Article  PubMed  CAS  Google Scholar 

  34. Crabtree GR. Contingent genetic regulatory events in T lymphocyte activation. Science 1989; 243: 355–361.

    Article  PubMed  CAS  Google Scholar 

  35. Kearney ER, Pape KA, Loh DY, Jenkins MK. Visualization of peptide-specific T cell immunity and peripheral tolerance in vivo. Immunity 1994; 1: 327–339.

    Article  PubMed  CAS  Google Scholar 

  36. Weaver CT, Saparov A, Kraus LA, Rogers WO, Hockett RD, Bucy RP. Heterogeneity in the clonal T cell response. Implications for models of T cell activation and cytokine phenotype development. Immunol Res 1998; 17: 279–302.

    Article  PubMed  CAS  Google Scholar 

  37. Bucy RP, Panoskaltsis-Mortari A, Huang GQ, et al. Heterogeneity of single cell cytokine gene expression in clonal T cell populations. J Exp Med 1994; 180: 1251–1262.

    Article  PubMed  CAS  Google Scholar 

  38. Bucy RP, Karr L, Huang GQ, et al. Single-cell analysis of cytokine gene co-expression during naive CD4+ T cell phenotype development. Proc Natl Acad Sci USA 1995; 92: 7565–7569.

    Article  PubMed  CAS  Google Scholar 

  39. Rogers WO, Weaver CT, Kraus LA, Li J, Li L, Bucy RP. Visualization of antigen specific T cell activation and cytokine expression in vivo. J Immunol 1997; 158: 649–657.

    PubMed  CAS  Google Scholar 

  40. Hosken NA, Shibuya K, Heath AW, Murphy KM, O’Garra A. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model. J Exp Med 1995; 182: 1579–1584.

    Article  PubMed  CAS  Google Scholar 

  41. Itoh Y, Germain RN. Single cell analysis reveals regulated hierarchial T cell antigen receptor signaling thresholds and intraclonal heterogeneity for individual cytokine responses of CD4+ T cells. J Exp Med 1997; 186: 757–766.

    Article  PubMed  CAS  Google Scholar 

  42. Swain SL, Weinberg AD, English M, Huston G. IL-4 directs the development of Th2-like helper effectors. J Immunol 1990; 145: 3796–3806.

    PubMed  CAS  Google Scholar 

  43. Hsieh, C-S, Heimberger AB, Gold JS, O’Garra A, Murphy KM. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an aß T-cell-receptor trans-genic system. Proc Natl Acad Sci USA 1993; 89: 6065–6069.

    Article  Google Scholar 

  44. Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O’Garra A, Murphy KM. Development of TH 1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 1993; 260: 547–549.

    Article  PubMed  CAS  Google Scholar 

  45. Seder RA, Paul WE, Davis MM, de St Groth BF. The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice. J Exp Med 1992; 176: 1091–1098.

    Article  PubMed  CAS  Google Scholar 

  46. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145–173.

    Article  PubMed  CAS  Google Scholar 

  47. Croft M, Carter L, Swain SL, Dutton, RW. Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles. J Exp Med 1994; 180: 1715–1728.

    Article  PubMed  CAS  Google Scholar 

  48. O’Garra A. Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 1998; 8: 275–283.

    Article  PubMed  Google Scholar 

  49. 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: 2348–2357.

    PubMed  CAS  Google Scholar 

  50. Street NE, Mosmann TR. Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J. 1991; 5: 171–177.

    PubMed  CAS  Google Scholar 

  51. 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: 2081–2095.

    Article  PubMed  CAS  Google Scholar 

  52. Gajewski TF, Fitch FW. Anti-proliferative effect of IFN gamma in immune regulation I. IFN gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol 1988; 140: 4245–4252.

    PubMed  CAS  Google Scholar 

  53. Schreiber RD, Hicks LJ, Celada A, Buchmeier NA, Gray PW. Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity. J Immunol 1985; 134: 1609–1618.

    PubMed  CAS  Google Scholar 

  54. Spitalny GL, Havell EA. Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities. J Exp Med 1984; 159: 1560–1565.

    Article  PubMed  CAS  Google Scholar 

  55. Cher DJ, Mosmann TR. Two types of murine helper cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol 1987; 138: 3688–3694.

    PubMed  CAS  Google Scholar 

  56. Fong TA, Mosmann TR. The role of IFN-gamma in delayed-type hypersensitivity mediated by Thl clones. J Immunol 1989; 143: 2887–2893.

    PubMed  CAS  Google Scholar 

  57. DeKruyff RH, Ju ST, Hunt AJ, Mosmann TR, Umetsu DT. Induction of antigen-specific antibody responses in primed and unprimed B cells. Functional heterogeneity among Thl and Th2 T-cell clones. J Immunol 1989; 142: 2575–2582.

    PubMed  CAS  Google Scholar 

  58. Croft M, Swain SL. B cell response to T helper cell subsets: II. Both the stage of T cell differentiation and the cytokines secreted determine the extent and nature of helper activity. J Immunol 1991; 147: 3679–3689.

    PubMed  CAS  Google Scholar 

  59. Fiorentino DF, Zlotnik A, Vieira P, et al. I1–10 acts on the antigen-presenting cell to inhibit cytokine production by Thl cells. J Immunol 1991; 146: 3444–3451.

    PubMed  CAS  Google Scholar 

  60. Yamamura M, Uyemura K, Deans RJ, et al. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 1991; 254: 277–279.

    Article  PubMed  CAS  Google Scholar 

  61. Henderson GS, Conray JT, Summar M, McCurley TL, Colley DG. In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. Il-4 mRNA, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymph nodes, and spleens of infected mice. J Immunol 1991; 147: 992–997.

    PubMed  CAS  Google Scholar 

  62. Holaday BJ, Sadick MD, Wang Z-E, et al. Reconstitution of Leishmania immunity in severe combined immunodeficient mice using Thl-and Th2-like cell lines. J Immunol 1991; 147: 1653–1658.

    PubMed  CAS  Google Scholar 

  63. Salgame P, Abrams JS, Clayberger C, et al. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T-cell clones. Science 1991; 254: 279–282.

    Article  PubMed  CAS  Google Scholar 

  64. Salgame P, Convit J, Bloom BR. Immunological suppression by human CD8+ T cells is receptor dependent and HLA-DQ restricted. Proc Natl Acad Sci USA 1991; 88: 2598–2602.

    Article  PubMed  CAS  Google Scholar 

  65. Sadick MD, Locksley RM, Tubbs C, Raff HV. Murine cutaneous leishmaniasis: resistance correlates with the capacity to generate interferon-gamma in response to Leishmania antigens in vitro. J Immunol 1986; 136: 655–661.

    PubMed  CAS  Google Scholar 

  66. Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM. 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. J Exp Med 1989; 169: 59–72.

    Article  PubMed  CAS  Google Scholar 

  67. Locksley RM, Heinzel FP, Holaday BJ, Mutha SS, Reiner SL, Sadick MD. Induction of Thl and Th2 CD4 + subsets during murine Leishmania major infection. Res Immunol 1991; 142: 28–32.

    Article  PubMed  CAS  Google Scholar 

  68. Coffman RL, Varkila K, Scott P, Chatelain R. Role of cytokines in the differentiation of CD4+ T-cell subsets in vivo. Immunol Rev 1991; 123: 189–207.

    Article  PubMed  CAS  Google Scholar 

  69. Kelso A. Thl and Th2 subsets: paradigms lost? Immunol Today 1995; 16: 374–379.

    Article  PubMed  CAS  Google Scholar 

  70. Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor ß after antigen-triggering. Proc Natl Acad Sci USA 1992; 89: 421–425.

    Article  PubMed  CAS  Google Scholar 

  71. Chen Y, Kuchroo VK, Inobe J, Hafler DA, Weiner HL. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 1994; 265: 1237–1240.

    Article  PubMed  CAS  Google Scholar 

  72. Groux H, O’Garra A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389: 737–742.

    Article  PubMed  CAS  Google Scholar 

  73. Modlin RL, Kato H, Mehra V, et al. Genetically restricted suppressor T-cell clones derived from lepromatous leprosy lesions. Nature 1986; 322: 459–461.

    Article  PubMed  CAS  Google Scholar 

  74. Bloom BR, Mehra V, Melancon Kaplan J, et al. Mechanisms of immunological unresponsiveness in the spectra of leprosy and leishmaniasis. Adv Exp Med Biol 1988; 239: 263–278.

    PubMed  CAS  Google Scholar 

  75. Guler ML, Gorham JD, Hsieh C-S, et al. Genetic susceptibility to Leishmania. IL-12 responsiveness in TH1 cell development. Science 1996; 271: 984–990.

    Article  PubMed  CAS  Google Scholar 

  76. Clerici M, Shearer GM. A TH1 -* TH2 switch is a critical step in the etiology of HIV infection. Immunol Today 1993; 14: 107–111.

    Article  PubMed  CAS  Google Scholar 

  77. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998; 396: 690–695.

    Article  PubMed  CAS  Google Scholar 

  78. Sprent J, Tough D. HIV results in the frame. CD4+ cell turnover. Nature 1995; 375: 194.

    Article  PubMed  CAS  Google Scholar 

  79. Mosier D. CD4+ cell turnover. Nature 1995; 375: 193–194.

    Article  PubMed  CAS  Google Scholar 

  80. Bucy RP, Hockett RD, Derdeyn CA, et al. Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest 1999; 103: 1391–1398.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. R. Pat Bucy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Goepfert
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. AIDS Center, Mount Sinai School of Medicine, New York, NY, USA

    Jeffrey M. Jacobson MD

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Bucy, R.P., Goepfert, P. (2002). Some Basic Cellular Immunology Principles Applied to the Pathogenesis of Infectious Diseases. In: Jacobson, J.M. (eds) Immunotherapy for Infectious Diseases. Infectious Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-171-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-171-8_2

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9681-9

  • Online ISBN: 978-1-59259-171-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation