THE HUMORAL IMMUNE-RESPONSE TO HAEMOPHILUS-INFLUENZAE TYPE-B - A MATHEMATICAL-MODEL BASED ON T-ZONE AND GERMINAL CENTER B-CELL DYNAMICS

Through careful mapping of the physiology of the T-zone and GC B-blast dynamics to a mathematical representation of the cell processes inclu ding proliferation, migration, differentiation, and cell death, a math ematical model is constructed to capture the dominant nominal primary, late follicular, and secondary humoral response to Haemophilus influe nzae Type b. This model explicitly incorporates the dynamics of memory B-cells, T-zone and GC B-dynamics, IgM and IgG antibodies, avidity ma turation, and IC presentation by FDCs into a coherent framework. This paper describes;the relevant immunology, the pertinent physiological a ssumptions, the developed model, and the parameter identification proc edure. The model parameters were found using a parameter identificatio n procedure that capitalizes on the timing and interactions of certain dominant physiological attributes. Simulation results and validation tests indicate that the model reflects not only a nominal primary and secondary humoral immune response but also the tertiary and T-independ ent responses. The model shows robustness to variations in infection d osage, bacterial growth rate (virulence of the strain), and onset-timi ng of the secondary response. The utility of this model in studying th e humoral immune response is demonstrated through suggested physiologi cal assumptions, mechanisms, and rates to be eventually clinically eva luated as well as insights into vaccination design. The model and para meter identification techniques are easily adapted to other diseases w hich primarily evoke a humoral immune response. (C) 1998 Academic Pres s.