A model for simulating cognate recognition and response in the immune system.

We have constructed a model of the immune system that focuses on the clonotypic cell types and their interactions with other cells, and with antigens and antibodies. We carry out simulations of the humoral immune system based on a generalized cellular automaton implementation of the model. We propose using computer simulation as a tool for doing experiments in machine, in the computer, as an adjunct to the usual in vivo and in vitro techniques. These experiments would not be intended to replace the usual biological experiments since, in the foreseeable future, a complete enough computer model capable of reliably simulating the whole immune would not be possible. However a model simulating areas of interest could be used for extensively testing ideas to help in the design of the critical biological experiments. Our present model concentrates on the cellular interactions and is quite adept at testing the importance and effects of cellular interactions with other cells, antigens and antibodies. The implementation is quite general and unrestricted allowing most other immune system components to be added with relative ease when desired.

[1]  Jerne Nk Towards a network theory of the immune system. , 1974 .

[2]  A. Macario,et al.  Low and High Affinity Antibodies Can Alternate during the Immune Response , 1973, Nature.

[3]  J A Hardin,et al.  Induction of autoreactive B cells allows priming of autoreactive T cells , 1991, The Journal of experimental medicine.

[4]  F Celada,et al.  The cellular basis of immunologic memory. , 1971, Progress in allergy.

[5]  N. Mitchison,et al.  Induction of immunological paralysis in two zones of dosage , 1964, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[6]  R. Riblet,et al.  Induction of antiphosphorylcholine antibody formation by anti-idiotypic antibodies , 1975, The Journal of experimental medicine.

[7]  Stephen Wolfram,et al.  Theory and Applications of Cellular Automata , 1986 .

[8]  H. Boehmer,et al.  Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes , 1988, Nature.

[9]  R. Schwartz,et al.  The Ia molecule of the antigen-presenting cell plays a critical role in immune response gene regulation of T cell activation. , 1983, The Journal of molecular and cellular immunology : JMCI.

[10]  Paul Manneville,et al.  Cellular Automata and Modeling of Complex Physical Systems , 1989 .

[11]  Joseph Puri,et al.  Mechanism of antigen binding by T cells: H‐2 (I‐A)‐restricted binding of antigen plus Ia by helper cells , 1980, European journal of immunology.

[12]  R M Zinkernagel,et al.  MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. , 1979, Advances in immunology.

[13]  F Celada,et al.  Differential activation of T cell clones stimulated by macrophages exposed to antigen complexed with monoclonal antibodies. A possible influence of paratope specificity on the mode of antigen processing. , 1988, Journal of immunology.

[14]  Göran Möller,et al.  ANTIBODY SYNTHESIS AT THE CELLULAR LEVEL. ANTIBODY-INDUCED SUPPRESSION OF 19S AND 7S ANTIBODY RESPONSE. , 1965 .

[15]  A. Perelson Immune Network Theory , 1989, Immunological reviews.

[16]  H. Boehmer,et al.  Positive selection of antigen-specific T cells in thymus by restricting MHC molecules , 1988, Nature.

[17]  Alan S. Perelson,et al.  The immune system, adaptation, and machine learning , 1986 .

[18]  A Sette,et al.  The Interaction between Protein‐Derived Immunogenic Peptides and Ia , 1987, Immunological reviews.

[19]  Franco Celada Quantitative studies of the adoptive immunological memory in mice. II. Linear transmission of cellular memory. , 1967 .

[20]  R. Zinkernagel,et al.  Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system , 1974, Nature.

[21]  Jeffrey Crosbie,et al.  Induction of self-tolerance in mature peripheral B lymphocytes , 1989, Nature.

[22]  F. Varela,et al.  Dynamics of a class of immune networks. I. Global stability of idiotype interactions. , 1990, Journal of theoretical biology.

[23]  E. Unanue,et al.  Antigenic competition at the level of peptide-Ia binding. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J Urbain,et al.  Idiotypic regulation of the immune system by the induction of antibodies against anti-idiotypic antibodies. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[25]  F. Varela,et al.  Second generation immune networks. , 1991, Immunology today.

[26]  P. Casali,et al.  CD5+ B lymphocytes, polyreactive antibodies and the human B-cell repertoire. , 1989, Immunology today.

[27]  A. Perelson,et al.  Size and connectivity as emergent properties of a developing immune network. , 1991, Journal of theoretical biology.

[28]  Gérard Weisbuch,et al.  Window automata analysis of population dynamics in the immune system. , 1992 .