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Register a new userAnalysis and optimal control of an intracellular delayed HIV model with CTL immune response
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Added by
Delfim F. M. Torres
Publication date
2018
fields
Biology
and research's language is
English
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A delayed model describing the dynamics of HIV (Human Immunodeficiency Virus) with CTL (Cytotoxic T Lymphocytes) immune response is investigated. The model includes four nonlinear differential equations describing the evolution of uninfected, infected, free HIV viruses, and CTL immune response cells. It includes also intracellular delay and two treatments (two controls). While the aim of first treatment consists to block the viral proliferation, the role of the second is to prevent new infections. Firstly, we prove the well-posedness of the problem by establishing some positivity and boundedness results. Next, we give some conditions that insure the local asymptotic stability of the endemic and disease-free equilibria. Finally, an optimal control problem, associated with the intracellular delayed HIV model with CTL immune response, is posed and investigated. The problem is shown to have an unique solution, which is characterized via Pontryagins minimum principle for problems with delays. Numerical simulations are performed, confirming stability of the disease-free and endemic equilibria and illustrating the effectiveness of the two incorporated treatments via optimal control.
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We propose and study a new mathematical model of the human immunodeficiency virus (HIV). The main novelty is to consider that the antibody growth depends not only on the virus and on the antibodies concentration but also on the uninfected cells concentration. The model consists of five nonlinear differential equations describing the evolution of the uninfected cells, the infected ones, the free viruses, and the adaptive immunity. The adaptive immune response is represented by the cytotoxic T-lymphocytes (CTL) cells and the antibodies with the growth function supposed to be trilinear. The model includes two kinds of treatments. The objective of the first one is to reduce the number of infected cells, while the aim of the second is to block free viruses. Firstly, the positivity and the boundedness of solutions are established. After that, the local stability of the disease free steady state and the infection steady states are characterized. Next, an optimal control problem is posed and investigated. Finally, numerical simulations are performed in order to show the behavior of solutions and the effectiveness of the two incorporated treatments via an efficient optimal control strategy.
Tumors constitute a wide family of diseases kinetically characterized by the co-presence of multiple spatio-temporal scales. So, tumor cells ecologically interplay with other kind of cells, e.g. endothelial cells or immune system effectors, producing and exchanging various chemical signals. As such, tumor growth is an ideal object of hybrid modeling where discrete stochastic processes model agents at low concentrations, and mean-field equations model chemical signals. In previous works we proposed a hybrid version of the well-known Panetta-Kirschner mean-field model of tumor cells, effector cells and Interleukin-2. Our hybrid model suggested -at variance of the inferences from its original formulation- that immune surveillance, i.e. tumor elimination by the immune system, may occur through a sort of side-effect of large stochastic oscillations. However, that model did not account that, due to both chemical transportation and cellular differentiation/division, the tumor-induced recruitment of immune effectors is not instantaneous but, instead, it exhibits a lag period. To capture this, we here integrate a mean-field equation for Interleukins-2 with a bi-dimensional delayed stochastic process describing such delayed interplay. An algorithm to realize trajectories of the underlying stochastic process is obtained by coupling the Piecewise Deterministic Markov process (for the hybrid part) with a Generalized Semi-Markovian clock structure (to account for delays). We (i) relate tumor mass growth with delays via simulations and via parametric sensitivity analysis techniques, (ii) we quantitatively determine probabilistic eradication times, and (iii) we prove, in the oscillatory regime, the existence of a heuristic stochastic bifurcation resulting in delay-induced tumor eradication, which is neither predicted by the mean-field nor by the hybrid non-delayed models.
Increasing number in global COVID-19 cases demands for mathematical model to analyze the interaction between the virus dynamics and the response of innate and adaptive immunity. Here, based on the assumption of a weak and delayed response of the innate and adaptive immunity in SARS-CoV-2 infection, we constructed a mathematical model to describe the dynamic processes of immune system. Integrating theoretical results with clinical COVID-19 patients data, we classified the COVID-19 development processes into three typical modes of immune responses, correlated with the clinical classification of mild & moderate, severe and critical patients. We found that the immune efficacy (the ability of host to clear virus and kill infected cells) and the lymphocyte supply (the abundance and pool of naive T and B cell) play important roles in the dynamic process and determine the clinical outcome, especially for the severe and critical patients. Furthermore, we put forward possible treatment strategies for the three typical modes of immune response. We hope our results can help to understand the dynamical mechanism of the immune response against SARS-CoV-2 infection, and to be useful for the treatment strategies and vaccine design.
Immune system is the most important defense system to resist human pathogens. In this paper we present an immune model with bipartite graphs theory. We collect data through COPE database and construct an immune cell- mediators network. The act degree distribution of this network is proved to be power-law, with index of 1.8. From our analysis, we found that some mediators with high degree are very important mediators in the process of regulating immune activity, such as TNF-alpha, IL-8, TNF-alpha receptors, CCL5, IL-6, IL-2 receptors, TNF-beta receptors, TNF-beta, IL-4 receptors, IL-1 beta, CD54 and so on. These mediators are important in immune system to regulate their activity. We also found that the assortative of the immune system is -0.27. It reveals that our immune system is non-social network. Finally we found similarity of the network is 0.13. Each two cells are similar to small extent. It reveals that many cells have its unique features. The results show that this model could describe the immune system comprehensive.
- In this paper we introduce a new method to solve fixed-delay optimal control problems which exploits numerical homotopy procedures. It is known that solving this kind of problems via indirect methods is complex and computationally demanding because their implementation is faced with two difficulties: the extremal equations are of mixed type, and besides, the shooting method has to be carefully initialized. Here, starting from the solution of the non-delayed version of the optimal control problem, the delay is introduced by numerical homotopy methods. Convergence results, which ensure the effectiveness of the whole procedure, are provided. The numerical efficiency is illustrated on an example.
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