Axioms of mathe- matical immunology

Current wisdom describes the immune system as a defense against microbial pathogens. It is claimed that the virgin immune system has a capacity to produce antibodies against the entire antigenic universe. We assume, by contrast, that the responding capacity of the immune system is limited. Thus it cannot stand in readiness to deal with a practi- cally endless diversity and abundance of microbes. Axioms and theorems are suggested for a mathematician audience delineating how the immune system could use its limited resources economically. It is suggested that the task of the immune system is twofold: (i) It sustains homeostasis to preserve the genome by constant surveillance of the intracellular antigenic milieu. This is achieved by standardization of the T cell repertoire through a positive selection. The driving force of positive selection is immune cell survival. T cells must constantly seek contact with complementary MHC structures to survive. Such contact is based on molecular complementarity between im...

[1]  K. Davies,et al.  Complement and immune complexes. , 2000, Methods in molecular biology.

[2]  G. Calandra,et al.  Vaccine induced immunologic memory for hepatitis B surface antigen: implications for policy on booster vaccination. , 1996, Vaccine.

[3]  M. Feinberg.  Changing the natural history of HIV disease , 1996, The Lancet.

[4]  I. Cohen,et al.  The cognitive principle challenges clonal selection. , 1992, Immunology today.

[5]  G. Mancardi,et al.  Soluble HLA Class I and Class II Molecule Levels in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients , 1997, Human Immunology.

[6]  R. Sorensen,et al.  Soluble histocompatibility class I antigens and beta 2-microglobulin in pregnant females and cord blood samples. , 1997, Human immunology.

[7]  M. Adler.  HIV: the other dimension , 1997, The Lancet.

[8]  A. Saphir.  Angiogenesis: the unifying concept in cancer? , 1997, Journal of the National Cancer Institute.

[9]  G. Michalopoulos,et al.  Liver Regeneration , 1997, Science.

[10]  C. McNeil.  HIV infection with Hodgkin's disease: the virus makes a difference. , 1997, Journal of the National Cancer Institute.

[11]  D Benton,et al.  Bioinformatics--principles and potential of a new multidisciplinary tool. , 1996, Trends in biotechnology.

[12]  M. Raff,et al.  Size Control: The Regulation of Cell Numbers in Animal Development , 1996, Cell.

[13]  K. Rock,et al.  Analysis of MHC class II presentation of particulate antigens of B lymphocytes. , 1996, Journal of immunology.

[14]  N. Pace.  A molecular view of microbial diversity and the biosphere. , 1997, Science.

[15]  B. Finlay,et al.  Exploitation of mammalian host cell functions by bacterial pathogens. , 1997, Science.

[16]  P. Schirmacher,et al.  Soluble IL-6 receptor leads to a paracrine modulation of the IL-6-induced hepatic acute phase response in double transgenic mice. , 1997, Journal of immunology.

[17]  P. Allen.  Peptides in positive and negative selection: A delicate balance , 1994, Cell.

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

[19]  D. Bonn.  Spared an influenza pandemic for another year? , 1997, The Lancet.

[20]  A S Perelson,et al.  Evolution and somatic learning in V-region genes. , 1996, Research in immunology.

[21]  R. Houghten,et al.  Probing degeneracy in T-cell recognition using peptide combinatorial libraries. , 1998, Immunology today.

[22]  D. Richman,et al.  HIV-1: Gambling on the evolution of drug resistance? , 1997, Nature Medicine.

[23]  T. Mertens,et al.  HIV and AIDS: where is the epidemic going? , 1996, Bulletin of the World Health Organization.

[24]  R. Phillips,et al.  Escape of human immunodeficiency virus from immune control. , 1997, Annual review of immunology.

[25]  T. Tada.  The immune system as a supersystem. , 1997, Annual review of immunology.

[26]  A. Berns,et al.  Peripheral T Cell Survival Requires Continual Ligation of the T Cell Receptor to Major Histocompatibility Complex–Encoded Molecules , 1997, The Journal of experimental medicine.

[27]  D. Margulies.  Interactions of TCRs with MHC-peptide complexes: a quantitative basis for mechanistic models. , 1997, Current opinion in immunology.

[28]  M. Sporn,et al.  Carcinogenesis and cancer: different perspectives on the same disease. , 1991, Cancer research.

[29]  P. Brandtzaeg,et al.  Microbial colonization influences composition and T‐cell receptor Vβ repertoire of intraepithelial lymphocytes in rat intestine , 1996, Immunology.

[30]  H. Takita,et al.  Antitumor immune response of human peripheral blood lymphocytes coengrafted with tumor into severe combined immunodeficient mice. , 1997, Cancer research.

[31]  Rita R. Colwell.  Global Climate and Infectious Disease: The Cholera Paradigm* , 1996, Science.

[32]  J. Sprent,et al.  Viruses and T Cell Turnover: Evidence for Bystander Proliferation , 1996, Immunological reviews.

[33]  G. Pasero,et al.  Hepatitis‐C virus infection and cabcer , 1997 .

[34]  B. Levin,et al.  Population biology, evolution, and infectious disease: convergence and synthesis. , 1999, Science.

[35]  P. Doherty,et al.  Quantitative analysis of the influenza virus-specific CD4+ T cell memory in the absence of B cells and Ig. , 1996, Journal of immunology.

[36]  G. Seledtsova,et al.  A possible role of pre‐existing IgM/IgG antibodies in determining immune response type , 1997, Immunology and cell biology.

[37]  R. Scheuermann,et al.  Cancer dormancy: Opportunities for new therapeutic approaches , 1997, Nature Medicine.

[38]  F. Schabel.  Concepts for systemic treatment of micrometastases , 1975, Cancer.

[39]  E. Brown,et al.  RENAL TRANSPLANTATION FOR DIALYSIS ARTHROPATHY , 1988, The Lancet.

[40]  K. Rajewsky.  Clonal selection and learning in the antibody system , 1996, Nature.

[41]  F. Chisari,et al.  To kill or to cure: options in host defense against viral infection. , 1996, Current opinion in immunology.

[42]  R. Garofalo,et al.  Antigen presentation of mucosal pathogens: the players and the rules. , 1997, International archives of allergy and immunology.

[43]  D Adams,et al.  How the immune system works and why it causes autoimmune diseases. , 1996, Immunology today.

[44]  P. Matzinger.  Tolerance, danger, and the extended family. , 1994, Annual review of immunology.

[45]  C. Janeway,et al.  On the semantics of immune recognition. , 1996, Research in immunology.

[46]  C. Janeway,et al.  Innate Immunity: The Virtues of a Nonclonal System of Recognition , 1997, Cell.

[47]  K. Johnson,et al.  Isolation of Machupo virus from wild rodent Calomys callosus. , 1966, American Journal of Tropical Medicine and Hygiene.

[48]  Robert Sim,et al.  An indirect effect of an antibody on complement deposition and lysis of differently sensitized surrounding cells. , 1994, Molecular immunology.

[49]  R. Zinkernagel,et al.  T helper cell‐independent neutralizing B cell response against vesicular stomatitis virus: Role of antigen patterns in B cell induction? , 1995, European journal of immunology.

[50]  S. Nathenson,et al.  Alloreactivity, Antigen Recognition and T‐Cell Selection: Three Diverse T‐Cell Recognition Problems with a Common Solution , 1996, Immunological reviews.

[51]  M. Kardar.  Which Came First, Protein Sequence or Structure? , 1996, Science.

[52]  T. Driscoll,et al.  Neocytolysis: physiological down-regulator of red-cell mass , 1997, The Lancet.

[53]  E. Fuchs.  Two signal model of lymphocyte activation. , 1992, Immunology today.

[54]  M. Redal,et al.  Soluble HLA class I antigens in pediatric patients with renal transplants from related living donors without acute rejection and treated with triple therapy. , 1996, Human immunology.

[55]  J. Bell,et al.  Engagement of a T cell receptor by major histocompatibility complex irrespective of peptide , 1997, European journal of immunology.

[56]  A. Dalgleish,et al.  SLIM DISEASE: A NEW DISEASE IN UGANDA AND ITS ASSOCIATION WITH HTLV-III INFECTION , 1985, The Lancet.

[57]  K. Tanaka,et al.  The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. , 1997, Journal of immunology.

[58]  J. Parsonnet.  Molecular mechanisms for inflammation-promoted pathogenesis of cancer--The Sixteenth International Symposium of the Sapporo Cancer Seminar. , 1997, Cancer research.

[59]  M. Sporn.  The war on cancer , 1996, The Lancet.

[60]  P. Allen,et al.  Structural basis for T cell recognition of altered peptide ligands: a single T cell receptor can productively recognize a large continuum of related ligands , 1996, The Journal of experimental medicine.

[61]  R. Root-Bernstein,et al.  Molecular complementarity I: the complementarity theory of the origin and evolution of life. , 1997, Journal of theoretical biology.

[62]  H. Pircher,et al.  On T Cell Memory: Arguments for Antigen Dependence , 1996, Immunological reviews.

[63]  P. Marrack,et al.  Detection of antigen-specific T cells with multivalent soluble class II MHC covalent peptide complexes. , 1998, Immunity.

[64]  M. Bevan,et al.  Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. , 1998, Immunity.

[65]  G. Rodier,et al.  Reemerging pathogens and diseases out of control , 1997, The Lancet.

[66]  H. G. Boman.  Peptide Antibiotics: Holy or Heretic Grails of Innate Immunity? , 1996, Scandinavian journal of immunology.

[67]  P. Marrack,et al.  T cells can be activated by peptides that are unrelated in sequence to their selecting peptide. , 1997, Immunity.

[68]  B. Rocha,et al.  Lymphocyte Survival: A Red Queen Hypothesis , 1997, Science.

[69]  C. Navarrete,et al.  The HLA System: An Update and Relevance to Patient‐Donor Matching Strategies in Clinical Transplantation , 1996, Vox sanguinis.

[70]  P. Doherty,et al.  Establishment and Persistence of Virus‐Specific CD4+ and CD8+ T Cell Memory , 1996, Immunological reviews.

[71]  G. Tusnády,et al.  Cold target competition analysis of the classical activation pathway of complement-mediated cytotoxicity: a non-interaction model for competing lysis. , 1992, Molecular immunology.

[72]  E. Turley,et al.  A new biological framework for cancer research , 1996, The Lancet.

[73]  Z. Grossman,et al.  Adaptive cellular interactions in the immune system: the tunable activation threshold and the significance of subthreshold responses. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[74]  J. Ferrara,et al.  The Immunopathophysiology of Acute Graft‐Versus‐Host‐Disease , 1996, Stem cells.

[75]  Péter Gács,et al.  Reliable computation with cellular automata , 1983, J. Comput. Syst. Sci..

[76]  Michael T. Wilson,et al.  Microbial/host interactions in health and disease: who controls the cytokine network? , 1996, Immunopharmacology.

[77]  T. Monath,et al.  Lassa Virus Isolation from Mastomys natalensis Rodents during an Epidemic in Sierra Leone , 1974, Science.

[78]  Russell W. Anderson,et al.  How adaptive antibodies facilitate the evolution of natural antibodies , 1996, Immunology and cell biology.

[79]  R. Strohman.  Profit margins and epistemology , 1997, Nature Biotechnology.

[80]  M. Neurath,et al.  Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin‐10 or antibodies to interleukin‐12 , 1996, European journal of immunology.

[81]  J. Butler.  Immunoglobulin Gene Organization and the Mechanism of Repertoire Development , 1997, Scandinavian journal of immunology.

[82]  M. Neurath,et al.  Responses to self and non-self intestinal microflora in health and inflammatory bowel disease. , 1997, Research in immunology.