The lymph node B cell immune response:: Dynamic analysis in-silico

被引:25
作者
Swerdlin, Naamah [1 ]
Cohen, Irun R. [2 ]
Harel, David [1 ]
机构
[1] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel
[2] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
基金
美国国家卫生研究院; 以色列科学基金会;
关键词
bottom-up modeling; emergent properties; lymph node; reactive animation; reactive system;
D O I
10.1109/JPROC.2008.925435
中图分类号
TM [电工技术]; TN [电子技术、通信技术];
学科分类号
0808 ; 0809 ;
摘要
Lymph nodes are organs in which lymphocytes respond to antigens to generate, among other cell types, plasma cells that secrete specific antibodies and memory lymphocytes for enhanced future responses to the antigen. To achieve these ends, the lymph node (LN) has to orchestrate the meeting and interactions between the antigen and various cell types including the rare clones of B cells and T cells bearing receptors for the antigen. The process is dynamic in essence and involves chemotaxis of responding cells through various anatomical compartments of the LN and selective cell differentiation, proliferation and programmed death. understanding the LN requires a dynamic integration of the mass of data generated by extensive experimentation. Here, we present a fully executable, bottom-up computerized model of the LN using the visual language of statecharts and the technology of reactive animation (RA) to create a dynamic front-end. we studied the effects of amount of antigen and LN size on the emergent properties of lymphocyte dynamics, differentiation and anatomic localization. The dynamic organization of the LN visualized by RA sheds new light on how the immune system transforms antigen stimulation into a highly sensitive, yet buffered response.
引用
收藏
页码:1421 / 1443
页数:23
相关论文
共 56 条
[11]   Toward rigorous comprehension of biological complexity: Modeling, execution, and visualization of thymic T-cell maturation [J].
Efroni, S ;
Harel, D ;
Cohen, LR .
GENOME RESEARCH, 2003, 13 (11) :2485-2497
[12]   Development and maturation of secondary lymphoid tissues [J].
Fu, YX ;
Chaplin, DD .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :399-433
[13]   Mathematical and computational models of immune-receptor signalling [J].
Goldstein, B ;
Faeder, JR ;
Hlavacek, WS .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (06) :445-456
[14]  
GROUARD G, 1995, J IMMUNOL, V155, P3345
[15]   STATECHARTS - A VISUAL FORMALISM FOR COMPLEX-SYSTEMS [J].
HAREL, D .
SCIENCE OF COMPUTER PROGRAMMING, 1987, 8 (03) :231-&
[16]   Executable object modeling with statecharts [J].
Harel, D ;
Gery, E .
COMPUTER, 1997, 30 (07) :31-&
[17]  
Harel D, 2005, CLIN INVEST MED, V28, P334
[18]  
Harel D, 2003, LECT NOTES COMPUT SC, V2852, P136
[19]  
HAREL D, 1985, NATO ASI SERIES F, V13, P477
[20]  
HAREL D, 2002, LECT NOTES INFORM P, V5, P11