CAM colloquium - Friday, February 2
3:30 p.m.
655 Rhodes Hall
Speaker: Ramit Mehr, The Mina and Everard Goodman Faculty of Life
Sciences
Bar-Ilan University, Israel & IRIS Center Microbiology, Tumor
and Cell Biology
Karolinska Institute, Sweden
Title: The Immune System - A Theoretician's View
Abstract: The immune response involves cells of
various types, including B, T and Natural Killer (NK) lymphocytes
expressing a large diversity of receptors which recognize foreign
antigens and self-molecules. The various cell types interact through
a complicated network of communication, regulation and control mechanisms.
This is what enables the immune system to perform the functions of
danger recognition, decision, action, memory and learning. As a result,
the dynamics of immune cell repertoires, in particular their development,
are highly complex and non-linear. Understanding the dynamics of lymphocyte
populations, immuno-receptor repertoire development and evolution,
is essential for elucidating the causes of various immune dysfunctions
and cancers.
We have addressed this issue by combining mathematical modeling of
cell population dynamics with experimental data, including BrdU labeling.
These studies revealed unexpected feedback mechanisms in T cell development
(Reviewed in Immunol. Today 1997, 18:581-585), phenotypic reflux in
B cell development (Mehr et al, Int’l Immunol. 2003, 15:301-312;
Gorfine et al, Bull. Math. Biol. 2003, 65:1131-1139), selection checkpoints
in transitional B cells (Shahaf et al, Int’l Immunol. 2004,
16:1081-1090) and the reasons for age-related decreased production
of T cells (Mehr et al, Mech. Age. Develop., 1993, 67:159-172; AGING:
Immunology and Infectious Disease, 1996, 6:133-140) and B cells (Shahaf
et al, Int’l Immunol. 2006, 18:31-39).
Furthermore, we have studied the development of B and T lymphocyte
repertoires (Mehr et al., J. Immunol., 1999, 163:1793-1798 and 1799-1808;
Kalmanovich & Mehr, 2003, J. Immunol., 170:182-193), Natural Killer
cell repertoire education (Reviewed in Salmon-Divon et al., Mol. Immunol.
2004, 42:397-403), and the within-host evolution of immunoglobulin
genes during an immune response (e.g., Shannon and Mehr, J. Immunol.,
1999, 162:3950-3956; Yaish & Mehr, Bull. Math. Biol., 67:15-32).
We combined modeling with novel immuno-informatical methods such as
quantification of lineage trees from B cell clones undergoing somatic
hypermutation (e.g., Dunn-Walters et al., Dev. Immunol. 2002, 9:233-245
and BioSystems 2004, 76:141-155; Mehr et al., J. Immunol. 2004, 172:4790-4796;
Horesh et al., J. Comp. Biol. 2006, 13:1165-1176), and applied these
new analyses to the study of humoral response changes in aging (Banerjee
et al., Eur. J. Immunol. 2002, 32:1947-1957), autoimmune diseases
(Steiman-Shimony et al., Autoimmun. Rev. 2006, 5:242-251) and B cell
malignancies (Manske et al., Clin Immunol. 2006, 120(1):106-120 ;
Abraham et al., J. Clin. Immunol., in press).
My talk will include a very brief introduction to the immune system,
and then focus on mathematical modeling of lymphocyte development
dynamics based on BrdU data.
Refreshments at 4:30 in 657 Rhodes Hall.