A. A. Romanyukha

Age related changes in population of peripheral T cells: towards a model of immunosenescence

In this paper, we presented the results of analysis of experimental evidence for the decline of the human immune system functioning with age using mathematical model of immunosenescence. The most prominent changes in this system are related to the decline in the T-cellular immunity. These include the decline in the nai;ve T cells generation rate, shrinkage of the volume of the peripheral lymphoid tissue, decline of absolute and relative concentrations of nai;ve T cells in the blood, shortening of the average telomere length of T cells. These alterations in the immune system are responsible for sharp increase of morbidity and mortality caused by infectious agents at old ages. Analysis shows that concentrations of memory and nai;ve T cells in peripheral lymphoid tissue are the key variables in this process. Simulation experiments with our model show that the average life span of memory T cells must grow with age, and that decreasing of antigenic load led to considerable increase in organisms resistance in middle ages, but only to slight increase in old ages. Restriction in the rate of thymus involution resulted in an increase of organisms resistance to infections in old ages. However, this growth is accompanied by the decline of concentration of memory T cells and shortening of their life span. The proposed model describes the trade-off between concentrations of nai;ve and memory T cells and their potential to proliferate in human organism.

The impact of diet switching on resource allocation to reproduction and longevity in Mediterranean fruitflies.

Understanding the factors that determine the allocation and utilization of organism resources may provide an insight into the mechanisms of adaptation, ageing and reproduction. Resource allocation, which is regarded as a method of adaptation, increases fitness and is genetically controlled. Experiments with variable diet feeding of female Mediterranean fruitflies (Ceratitis capitata) demonstrated that the feeding regime dramatically influences lifespan, mortality and the reproduction of flies. An analysis of experimental data and numerical experiments reveals that resource allocation could explain lifespan increase when females are switched from a sugar–only to a protein–containing diet. The heterogeneity of the initial female cohort in terms of the total amount of resources and its allocation to the processes of maintenance and reproduction plays a significant role in this.

Mathematical modeling of tuberculosis propagation and patient detection

A mathematical model of the spread of tuberculosis taking into account the impact of the antituberculosis programs was considered. The singularity of the proposed model lies in making explicit discrimination between the detected and overlooked patients and taking into account their migration. Studies demonstrated insufficiency of the standard accounting form of the regional Russian antituberculosis institutions. Proposed was a submodel enabling objective estimation of the patient detection system on the basis of individualized database. These estimates corroborated the assumption of a substantial nonuniformity of the Russian regions in terms of tuberculosis morbidity and efficiency of patient detection. For example, the rates of patient detection can differ by the factor of five through six. The model can be used to forecast the tuberculosis morbidity and efficiency of the antituberculosis programs.

Immune system aging may be affected by HIV infection: the mathematical model of immunosenescence

In this paper, we analyse the structure of equations in the earlier proposed mathematical model of the dynamics of age-related changes in population of peripheral T lymphocytes. To investigate behaviour of the model solutions in a wide range of values of variables we introduce a linear relation between the rate constants of T lymphocytes proliferation and the values of the mean length of telomeric chromosome fragments spent by naive and memory cells in the course of immune response, as well as the dependence of these parameters on the value of the cell replicative potential. We obtain sufficient conditions for existence, uniqueness, and positiveness of solutions over the whole time interval. The results of numerical calculations illustrate the capabilities of the model for describing accelerated aging mechanisms of the immune system using the example of HIV infection.

Evaluating the efficiency of cell mechanisms and systems

We propose an approach for estimating the efficiency of biological systems and mechanisms in vivo. We compare two mechanisms for chemical transport: diffusion and endosome transport with a cargo along a system of microtubules. Our efficiency evaluation is based on a comparison of the organism’s energy expenditure for cell house-keeping and the transport system’s operation with the speed of cargo delivery. We study the relation between transport efficiency and adaptability of the transport network. Our approach can be used to study models of live systems and solve problems of artificial life design.

Modeling spread of HIV as a result of social maladjustment

The aim of the research is to develop methods for evaluation of effectiveness of human immunodeficiency virus (HIV) spread counteraction measures for Russia. The regional inequity in HIV prevalence is closely linked with the inequity in prevalence of alcohol and drug abuse which can be considered as a value of social maladjustment in population. Taking into account influence of these processes on formation of HIV high-risk groups permits to describe the regional inequity in epidemic proportions and evaluate effectiveness of counteraction measures. The social-epidemiological model of HIV spread and the problem of model parameter identification by the data of Russian regions are examined in the paper.

Mathematical Modeling of Immunosenescence: Scenarios, Processes and Limitations

Mathematical modeling of immunosenescence is the new area of research emerging at the interface of the immunology, gerontology, and mathematics. In this paper we outline basic variables important for modeling aging immunity. We discuss the role of evolution in shaping pattern of aging in the immune system of modern humans. We investigate mathematical models of postnatal changes in the population of peripheral T-cells, effects of the antigenic load during development on the body growth, and contribution of immunosenescence to the old age increase in the risk of death from respiratory infections.

The Energy Criterion for Quality of Immune Defence and Pathogenicity of Microorganisms

Relationships between the energy cost of immune defence, the disease severity, and the properties of pathogens were investigated. The findings suggested a hypothesis explaining the observed distribution of microorganism pathogenicity. The mechanism supporting stability of this distribution explains emergence of new highly pathogenic strains of microorganisms.