Mathematical modeling suggests heterogeneous replication of Mycobacterium tuberculosis in rabbits.

Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), remains a major health problem with 10.6 million cases of the disease and 1.6 million deaths in 2021.

Appropriate Sampling and Longer Follow-Up Are Required to Rigorously Evaluate Longevity of Humoral Memory After Vaccination.

One of the goals of vaccination is to induce long-lived immunity against the infection and/or disease. Many studies have followed the generation of humoral immunity to SARS-CoV-2 after vaccination; however, such studies typically varied by the duration of the follow-up and the number of time points at which immune response measurements were done. How these parameters (the number of time points and the overall duration of the follow-up) impact estimates of immunity longevity remain largely unknown.

Mathematical modeling suggests heterogeneous replication of in rabbits.

Tuberculosis (), the disease caused by (), remains a major health problem with 10.6 million cases of the disease and 1.6 million deaths in 2021.

Heterogeneity in killing efficacy of individual effector CD8 T cells against Plasmodium liver stages.

Vaccination strategies in mice inducing high numbers of memory CD8 T cells specific to a single epitope are able to provide sterilizing protection against infection with Plasmodium sporozoites. We have recently found that Plasmodium-specific CD8 T cells cluster around sporozoite-infected hepatocytes but whether such clusters are important in elimination of the parasite remains incompletely understood. Here, we used our previously generated data in which we employed intravital microscopy to longitudinally image 32 green fluorescent protein (GFP)-expressing parasites in livers of mice that had received activated Plasmodium-specific CD8 T cells after sporozoite infection.

Brain-localized CD4 and CD8 T cells perform correlated random walks and not Levy walks.

For survival of the organism, T cells must efficiently control pathogens invading different peripheral tissues. Whether or not such control is achieved by utilizing different movement strategies in different tissues remains poorly understood. Liver-localized CD8 T cells perform correlated random walks  --- a type of a Brownian walk -- in liver sinusoids but in some condition these T cells may also perform Levy flights -- rapid and large displacements by floating with the blood flow.

Cytotoxic T Lymphocytes Control Growth of B16 Tumor Cells in Collagen-Fibrin Gels by Cytolytic and Non-Lytic Mechanisms.

Cytotoxic T lymphocytes (CTLs) are important in controlling some viral infections, and therapies involving the transfer of large numbers of cancer-specific CTLs have been successfully used to treat several types of cancers in humans. While the molecular mechanisms of how CTLs kill their targets are relatively well understood, we still lack a solid quantitative understanding of the kinetics and efficiency by which CTLs kill their targets in vivo. Collagen-fibrin-gel-based assays provide a tissue-like environment for the migration of CTLs, making them an attractive system to study T cell cytotoxicity in in vivo-like conditions.

Appropriate sampling and long follow-up are required to rigorously evaluate longevity of humoral memory after Vaccination.

One of the goals of vaccination is to induce long-term immunity against the infection and/or disease. However, evaluating the duration of protection following vaccination often requires long-term follow-ups that can conflict with the desire to rapidly publish results. Arunachalam et al.

Prioritization of the concepts and skills in quantitative education for graduate students in biomedical science.

Substantial guidance is available on undergraduate quantitative training for biologists, including reports focused on biomedical science. Far less attention has been paid to the graduate curriculum and the particular challenges of the diversity of specialization within the life sciences. We propose an innovative approach to quantitative education that goes beyond recommendations of a course or set of courses or activities, derived from analysis of the expectations for students in particular programs.

Mathematical modeling suggests cytotoxic T lymphocytes control growth of B16 tumor cells in collagin-fibrin gels by cytolytic and non-lytic mechanisms.

Cytotoxic T lymphocytes (CTLs) are important in controlling some viral infections, and therapies involving transfer of large numbers of cancer-specific CTLs have been successfully used to treat several types of cancers in humans. While molecular mechanisms of how CTLs kill their targets are relatively well understood we still lack solid quantitative understanding of the kinetics and efficiency at which CTLs kill their targets in different conditions. Collagen-fibrin gel-based assays provide a tissue-like environment for the migration of CTLs, making them an attractive system to study the cytotoxicity in vitro.

Correlation between speed and turning naturally arises for sparsely sampled cell movements.

Mechanisms regulating cell movement are not fully understood. One feature of cell movement that determines how far cells displace from an initial position is persistence, the ability to perform movements in a direction similar to the previous movement direction. Persistence is thus determined by turning angles (TA) between two sequential displacements and can be characterized by an average TA or persistence time.

A New Method Based on the von Mises-Fisher Distribution Shows that a Minority of Liver-Localized CD8 T Cells Display Hard-To-Detect Attraction to -Infected Hepatocytes.

Malaria is a disease caused by parasites, resulting in over 200 million infections and 400,000 deaths every year. A critical step of malaria infection is when sporozoites, injected by mosquitoes, travel to the liver and form liver stages. Malaria vaccine candidates which induce large numbers of malaria-specific CD8 T cells in mice are able to eliminate all liver stages, preventing fulminant malaria.

Mathematical Modeling to Guide Experimental Design: T Cell Clustering as a Case Study.

Mathematical modeling provides a rigorous way to quantify immunological processes and discriminate between alternative mechanisms driving specific biological phenomena. It is typical that mathematical models of immunological phenomena are developed by modelers to explain specific sets of experimental data after the data have been collected by experimental collaborators. Whether the available data are sufficient to accurately estimate model parameters or to discriminate between alternative models is not typically investigated.

Interactions with Asialo-Glycoprotein Receptors and Platelets Are Dispensable for CD8 T Cell Localization in the Murine Liver.

Liver-resident CD8 T cells can play critical roles in the control of pathogens, including and hepatitis B virus. Paradoxically, it has also been proposed that the liver may act as the main place for the elimination of CD8 T cells at the resolution of immune responses. We hypothesized that different adhesion processes may drive residence versus elimination of T cells in the liver.

Mathematical Modeling Suggests Cooperation of Plant-Infecting Viruses.

Viruses are major pathogens of agricultural crops. Viral infections often start after the virus enters the outer layer of a tissue, and many successful viruses, after local replication in the infected tissue, are able to spread systemically. Quantitative details of virus dynamics in plants, however, are poorly understood, in part, because of the lack of experimental methods which allow the accurate measurement of the degree of infection in individual plant tissues.

Liver Environment-Imposed Constraints Diversify Movement Strategies of Liver-Localized CD8 T Cells.

Pathogen-specific CD8 T cells face the problem of finding rare cells that present their cognate Ag either in the lymph node or in infected tissue. Although quantitative details of T cell movement strategies in some tissues such as lymph nodes or skin have been relatively well characterized, we still lack quantitative understanding of T cell movement in many other important tissues, such as the spleen, lung, liver, and gut. We developed a protocol to generate stable numbers of liver-located CD8 T cells, used intravital microscopy to record movement patterns of CD8 T cells in livers of live mice, and analyzed these and previously published data using well-established statistical and computational methods.

Impact of Oseltamivir Treatment on Influenza A and B Virus Dynamics in Human Volunteers.

Influenza viruses infect millions of humans every year causing an estimated 400,000 deaths globally. Due to continuous virus evolution current vaccines provide only limited protection against the flu. Several antiviral drugs are available to treat influenza infection, and one of the most commonly used drugs is oseltamivir (Tamiflu).

Treatment timing shifts the benefits of short and long antibiotic treatment over infection.

Antibiotics are the major tool for treating bacterial infections. Rising antibiotic resistance, however, calls for a better use of antibiotics. While classical recommendations favor long and aggressive treatments, more recent clinical trials advocate for moderate regimens.

Ultra-low Dose Aerosol Infection of Mice with Mycobacterium tuberculosis More Closely Models Human Tuberculosis.

Tuberculosis (TB) is a heterogeneous disease manifesting in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). Unlike human TB, murine infection results in uniformly high lung bacterial burdens and poorly organized granulomas. To develop a TB model that more closely resembles human disease, we infected mice with an ultra-low dose (ULD) of between 1-3 founding bacteria, reflecting a physiologic inoculum.

Experimental determination of the force of malaria infection reveals a non-linear relationship to mosquito sporozoite loads.

Plasmodium sporozoites are the infective stage of the malaria parasite. Though this is a bottleneck for the parasite, the quantitative dynamics of transmission, from mosquito inoculation of sporozoites to patent blood-stage infection in the mammalian host, are poorly understood. Here we utilize a rodent model to determine the probability of malaria infection after infectious mosquito bite, and consider the impact of mosquito parasite load, blood-meal acquisition, probe-time, and probe location, on infection probability.

Clustering of Activated CD8 T Cells Around Malaria-Infected Hepatocytes Is Rapid and Is Driven by Antigen-Specific Cells.

Malaria, a disease caused by parasites of the Plasmodium genus, begins when Plasmodium-infected mosquitoes inject malaria sporozoites while searching for blood. Sporozoites migrate from the skin via blood to the liver, infect hepatocytes, and form liver stages which in mice 48 h later escape into blood and cause clinical malaria. Vaccine-induced activated or memory CD8 T cells are capable of locating and eliminating all liver stages in 48 h, thus preventing the blood-stage disease.

Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes.

The ability of lymphocytes to recirculate between blood and secondary lymphoid tissues such as lymph nodes (LNs) and spleen is well established. Sheep have been used as an experimental system to study lymphocyte recirculation for decades and multiple studies document accumulation and loss of intravenously (i.v.

T follicular helper cells in human efferent lymph retain lymphoid characteristics.

T follicular helper cells (Tfh), a subset of CD4+ T cells, provide requisite help to B cells in the germinal centers (GC) of lymphoid tissue. GC Tfh are identified by high expression of the chemokine receptor CXCR5 and the inhibitory molecule PD-1. Although more accessible, blood contains lower frequencies of CXCR5+ and PD-1+ cells that have been termed circulating Tfh (cTfh).

The Rate of CD4 T Cell Entry into the Lungs during Mycobacterium tuberculosis Infection Is Determined by Partial and Opposing Effects of Multiple Chemokine Receptors.

The specific chemokine receptors utilized by Th1 cells to migrate into the lung during infection are unknown. We previously showed in mice that CXCR3 Th1 cells enter the lung parenchyma and suppress growth, while CX3CR1 KLRG1 Th1 cells accumulate in the lung vasculature and are nonprotective. Here we quantify the contributions of these chemokine receptors to the migration and entry rate of Th1 cells into -infected lungs using competitive adoptive transfer migration assays and mathematical modeling.

Defining Kinetic Properties of HIV-Specific CD8⁺ T-Cell Responses in Acute Infection.

Multiple lines of evidence indicate that CD8 + T cells are important in the control of HIV-1 (HIV) replication. However, CD8 + T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8 + T-cell responses induced during HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8 + T-cell responses, must exceed.