Search

This paper studies the global stability of a general discrete-time viral infection model with virus-to-cell and cell-to-cell transmissions and with humoral immune response. We consider both latently and actively infected cells. The model incorporates three types of intracellular time delays. The production and clearance rates of all compartments as well as incidence rates of infection are modeled by general nonlinear functions. We use the nonstandard finite difference method to discretize the continuous-time model. We show that the solutions of the discrete-time model are positive and ultimately bounded. We derive two threshold parameters, the basic reproduction number R 0 and the humoral immune response activation number R 1 , which completely determine the existence and stability of the model's equilibria. By using Lyapunov functions, we have proven that if R 0 ≤ 1 , then the virus-free equilibrium Q0 is globally asymptotically stable; if R 1 ≤ 1 < R 0 , then the persistent infection equilibrium without immune response Q* is globally asymptotically stable; and if R 1 > 1 , then the persistent infection equilibrium with immune response Q ¯ is globally asymptotically stable. We illustrate our theoretical results by using numerical simulations. The effects of antiretroviral drug therapy and time delay on the virus dynamics are also studied. We have shown that the time delay has a similar effect as the antiretroviral drug therapy. [ABSTRACT FROM AUTHOR]

Monocytes represent a class of immune cells that play a key role in the innate and adaptive immune response against infections. One mechanism employed by monocytes for sensing foreign antigens is via toll-like receptors (TLRs)--transmembrane proteins that distinguish classes of foreign pathogens, for example, bacteria (TLR4, 5, and 9) vs. fungi (TLR2) vs. viruses (TLR3, 7, and 8). Binding of antigens activates a signaling cascade through TLR receptors that culminate in secretion of inflammatory cytokines. Detection of these cytokines can provide valuable clinical data for drug developers and disease investigations, but this usually requires a large sample volume and can be technically inefficient with traditional techniques such as flow cytometry, enzyme-linked immunosorbent assay, or luminex. This paper describes an approach whereby antibody arrays for capturing cells and secreted cytokines are encapsulated within a microfluidic device that can be reconfigured to operate in serial or parallel mode. In serial mode, the device represents one long channel that may be perfused with a small volume of minimally processed blood. Once monocytes are captured onto antibody spots imprinted into the floor of the device, the straight channel is reconfigured to form nine individually perfusable chambers. To prove this concept, the microfluidic platform was used to capture monocytes from minimally processed human blood in serial mode and then to stimulate monocytes with different TLR agonists in parallel mode. Three cytokines, tumor necrosis factor-a, interleukin (IL)-6, and IL-10, were detected using anti-cytokine antibody arrays integrated into each of the six chambers. We foresee further use of this device in applications such as pediatric immunology or drug/vaccine testing where it is important to balance small sample volume with the need for high information content. [ABSTRACT FROM AUTHOR]

This paper examines the interplay of the effect of cross immunity and antibody-dependent enhancement (ADE) in multistrain diseases. Motivated by dengue fever, we study a model for the spreading of epidemics in a population with multistrain interactions mediated by both partial temporary cross immunity and ADE. Although ADE models have previously been observed to cause chaotic outbreaks, we show analytically that weak cross immunity has a stabilizing effect on the system. That is, the onset of disease fluctuations requires a larger value of ADE with small cross immunity than without. However, strong cross immunity is shown numerically to cause oscillations and chaotic outbreaks even for low values of ADE. [ABSTRACT FROM AUTHOR]