Abstract
Administered antibodies can suppress humoral immune response. Though there are two hypotheses explaining the suppression, such as the epitope-masking and Fc-receptor mediated suppression, the epitope-masking hypothesis has garnered more supports. To better understand how the immune suppression works and to gain a quantitative and qualitative insight, we developed the first mathematical immune suppression model based on the epitope-masking hypothesis. However, because the hypothesis does not account for the actual B suppression mechanism, the fact that antigen-depletion induces the arrest of proliferating B cells was incorporated to the model. The model can reproduce immune suppression phenomena and complement the epitope-masking hypothesis by suggesting that the key mechanism for the suppression is the arrest of proliferating B cells and it was shown to be feasible. It is expected that our model gives a new insight to researchers in designing experiments for discovering the underlying mechanism of immune suppression.
This work was supported by National Research Laboratory Grant (2005-01450) from the Ministry of Science and Technology. We would like to thank CHUNG Moon Soul Center for BioInformation and BioElectronics and the IBM-SUR program for providing research and computing facilities.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Tao, T., Uhr, J.W.: Capacity of pepsin-digested antibody to inhibit antibody formation. Nature 212, 208–209 (1966)
Chilcott, J., Jones, M.L., Wight, J., Forman, K., Wray, J., Beverley, C., Tappenden, P.: A review of the clinical effectiveness and cost-effectiveness of routine anti-D prophylaxis for pregnant women who are rhesus-negative. Health Technol. Assess. 7, iii-62 (2003)
Gottvall, T., Selbing, A.: Alloimmunization during pregnancy treated with high dose intravenous immunoglobulin. Effects on fetal hemoglobin concentration and anti-D concentrations in the mother and fetus. Acta Obstet. Gynecol. Scand. 74, 777–783 (1995)
Karlsson, M.C.I., de Ståhl, T.D., Heyman, B.: IgE-mediated suppression of primary antibody response in vivo. Scand. J. Immunol. 53, 381–385 (2001)
Heyman, B., Dahlström, J., de Ståhl, T.D., Getahun, A., Wernersson, S., Karlsson, M.C.I.: No evidence for a role of FcγRIIB in suppression of in vivo antibody response to erythrocytes by passively administered IgG. Scand. J. Immunol. 53, 331–334 (2001)
Cerottini, J.C., McConahey, P.J., Dixon, F.J.: The immunosuppressive effect of passively administered antibody IgG fragments. J. Immunol. 102, 1008–1015 (1969)
Quintana, I.Z., Silveira, A.V., Möller, G.: Regulation of the antibody response to sheep erythrocytes by monoclonal Ig antibodies. Eur. J. Immunol. 17, 1343–1349 (1987)
Ravetch, J.V., Lanier, L.L.: Immune inhibitory receptors. Science 290, 84–89 (2000)
Coggeshall, K.M.: Inhibitory signaling by B cell FcγRIIb. Curr. Opin. Immunol. 10, 306–312 (1998)
Heyman, B.: Fc-dependent IgG-mediated suppression of the antibody response: fact or artifact? Scand. J. Immunol. 31, 601–607 (1990)
Karlsson, M.C.I., Wernersson, S., de Ståhl, T.D., Gustavsson, S., Heyman, B.: Efficient IgG-mediated suppression of primary antibody responses in Fcγ receptor-deficient mice. Proc. Natl. Acad. Sci. 96, 2244–2249 (1999)
Karlsson, M.C.I., Getahun, A., Heyman, B.: FcγRIIB in IgG-mediated suppression of antibody responses: different impact in vivo and in vitro. J. Immunol. 167, 5558–5564 (2001)
Marino, S., Kirschner, D.E.: The human immune response to Mycobacterium tuberculosis in lung and lymph node. J. Theor. Biol. 227, 463–486 (2004)
Funk, G.A., Barbour, A.D., Hengartner, H., Kalinke, U.: Mathematical model of a virus-neutralizing immunoglobulin response. J. Ttheor. Biol. 195, 41–52 (1998)
Rundell, A., DeCarlo, R., Hogenesch, H., Doerschuk, P.: The humoral immune response to Haemophilus influenzae type b: a mathematical model based on T-zone and germinal center B-cell dynamics. J. Theor. Biol. 194, 341–381 (1998)
Davenport, M.P., Fazou, C., McMichael, A.J., Callan, M.F.C.: Clonal selection, clonal senescence, and clonal succession: the evolution of the T cell response to infection with a persistent virus. J. Immunol. 168, 3309–3317 (2002)
De Boer, R.J., Oprea, M., Antia, R., Murali-Krishna, K., Ahmed, R., Perelson, A.S.: Recruitment times, proliferation, and apoptosis rates during the CD8+ T-cell response to lymphocytic choriomeningitis virus. J. Virol. 75, 10663–10669 (2001)
Wodarz, D., Lloyd, A.L., Jansen, V.A.A., Nowak, M.A.: Dynamics of macrophage and T cell infection by HIV. J. Theor. Biol. 196, 101–113 (1999)
Stafford, M.A., Corey, L., Cao, Y., Daar, E.S., Ho, D.D., Perelson, A.S.: Modeling plasma virus concentration during primary HIV infection. J. Theor. Biol. 203, 285 (2000)
Perelson, A.S.: Modelling viral and immune system dynamics. Nat. Rev. Immunol. 2, 28–36 (2002)
Heyman, B.: Feedback regulation by IgG antibodies. Immunol. Lett. 88, 157–161 (2003)
Rosado, M.M., Freitas, A.A.: The role of the B cell receptor V region in peripheral B cell survival. Eur. J. Immunol. 28, 2685–2693 (1998)
Pittner, B.T., Snow, E.C.: Strength of signal through BCR determines the fate of cycling B cells by regulating the expression of the Bcl-2 family of survival proteins. Cell. Immunol. 186, 55–62 (1998)
Smith, S.H., Reth, M.: Perspectives on the nature of BCR-mediated survival signals. Mol. Cell. 14, 696–697 (2004)
Hodgkin, P.D., Lee, J., Lyons, A.B.: B cell differentiation and isotype switching is related to division cycle number. J. Exp. Med. 184, 277–281 (1996)
Hager, A.-C.M., Ellmark, P., Borrebaeck, C.A.K., Furebring, C.: Affinity and epitope profiling of mouse anti-CD40 monoclonal antibodies. Scand. J. Immunol. 57, 517–524 (2003)
Kierzek, A.M., Zaim, J., Zielenkiewicz, P.: The effect of transcription and translation initiation frequencies on the stochastic fluctuations in prokaryotic gene expression. J. Biol. Chem. 276, 8165–8172 (2001)
Perelson, A.S.: Immunology for physicists. Rev. Modern Phys. 69, 1219–1268 (1997)
Maynard, J., Georgiou, G.: Antibody engineering. Annu. Rev. Biomed. Eng. 2, 339–376 (2000)
Giles Jr., R.C., Berman, A., Hildebrandt, P.K., McCaffrey, R.P.: The use of 51Cr for sheep red blood cell survival studies. Proc. Soc. Exp. Biol. Med. 148, 795–798 (1975)
Leanderson, T., Källberg, E., Gray, D.: Expansion, selection and mutation of antigen-specific B-cells in germinal centers. Immunol. Rev. 126, 47–61 (1992)
Bocharov, G.A., Romanyukha, A.A.: Mathematical model of antiviral immune response III. Influenza A virus infection. J. Theor. Biol. 167, 323–360 (1994)
Göran Möller, M.D., Wigzell, H.: Antibody synthesis at the cellular level. J. Exp. Med. 121, 969–989 (1965)
Heyman, B., Wigzell, H.: Immunoregulation by monoclonal sheep erythrocyte-specific IgG antibodies: suppression is correlated to level of antigen binding and not to isotype. J. Immunol. 132, 1136–1143 (1984)
Kettman, J., Dutton, R.W.: An in vitro primary immune response to 2,4,6-trinitrophenyl substituted erythrocytes: response against carrier and hapten. J. Immunol. 104, 1558–1561 (1970)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Na, D., Lee, D. (2005). Mathematical Modeling of Immune Suppression. In: Jacob, C., Pilat, M.L., Bentley, P.J., Timmis, J.I. (eds) Artificial Immune Systems. ICARIS 2005. Lecture Notes in Computer Science, vol 3627. Springer, Berlin, Heidelberg. https://doi.org/10.1007/11536444_14
Download citation
DOI: https://doi.org/10.1007/11536444_14
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-28175-7
Online ISBN: 978-3-540-31875-0
eBook Packages: Computer ScienceComputer Science (R0)