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Biomedical subjects

P W Price

Publications and source records attributed to P W Price.

9 recordsLinked to original sources

Rickettsia-macrophage interactions: host cell responses to Rickettsia akari and Rickettsia typhi.

The existence of intracellular rickettsiae requires entry, survival, and replication in the eukaryotic host cells and exit to initiate new infection. While endothelial cells are the preferred target cells for most pathogenic rickettsiae, infection of monocytes/macrophages may also contribute to the establishment of rickettsial infection and resulting pathogenesis. We initiated studies to characterize macrophage-Rickettsia akari and -Rickettsia typhi interactions and to determine how rickettsiae survive within phagocytic cells. Flow cytometry, microscopic analysis, and LDH release demonstrated that R. akari and R. typhi caused negligible cytotoxicity in mouse peritoneal macrophages as well as in macrophage-like cell line, P388D1. Host cells responded to rickettsial infection with increased secretion of proinflammatory cytokines such as interleukin-1beta (IL-1beta) and IL-6. Furthermore, macrophage infection with R. akari and R. typhi resulted in differential synthesis and expression of IL-beta and IL-6, which may correlate with the existence of biological differences among these two closely related bacteria. In contrast, levels of gamma interferon (IFN-gamma), IL-10, and IL-12 in supernatants of infected P388D1 cells and mouse peritoneal macrophages did not change significantly during the course of infection and remained below the enzyme-linked immunosorbent assay cytokine detection limits. In addition, differential expression of cytokines was observed between R. akari- and R. typhi-infected macrophages, which may correlate with the biological differences among these closely related bacteria.

Animals↗

Host-driven population dynamics in an herbivorous insect.

Understanding the nature and relative importance of endogenous (density-dependent) and exogenous (density-independent) effects on population dynamics remains a central problem in ecology. Evaluation of these forces has been constrained by the lack of long time series of population densities and largely limited to populations chosen for their unique dynamics (e.g., outbreak insects). Especially in herbivore populations, the relative contributions of bottom-up and top-down effects (resources and natural enemies, respectively) have been difficult to compare because population data have rarely been combined with resource measurements. The feeding scars of a wood-mining herbivorous insect (Phytobia betulae Kangas; Diptera: Agromyzidae) of birch trees (Betula pendula and Betula pubescens) provided long time series data (47 and 65 years) of absolute abundance (larvae/tree) in replicated trees within replicated stands. Measurements of tree annual rings provided matching time series of host age and physiological status. Analyses showed a powerful exogenous effect of stand age on temporal variation in insect abundance (58 and 32% of the variance in two populations, respectively). With the additional effects of variation among trees, 77 and 64% of the total variance in abundance was attributable to exogenous bottom-up effects of host plants. Potential endogenous effects were evident as immediate linear density dependence, but only accounted for approximately 10% of the total variance. Abundance of Phytobia is primarily a function of disturbance history, which produces a mosaic of different aged birch stands that harbor Phytobia populations of different sizes. Density-dependence tends to regulate local populations around levels determined by host suitability.

Animals↗

Characterization of CD4+ T cells in mouse bone marrow. I. Increased activated/memory phenotype and altered TCR Vbeta repertoire.

A significant proportion of memory B cells home to bone marrow (BM) which is a major site of anamnestic antibody responses in mice. We hypothesized that memory T cells likewise accumulate in BM perhaps to provide help for antibody production, and that the compartment of CD4+ T cells in BM of unimmunized mice would be enriched for memory phenotype cells that might have been activated by environmental antigens. The phenotype of activated/memory CD4+ lymphocytes has been defined as CD44hi CD45RBlo CD62L-. Conversely, the phenotype of immunologically naive cells is CD44lo CD45RBhi CD62L+. Flow cytrometric analysis of tissue from normal, adult C57BL/6 mice identified 1-2 % CD3+CD4+ cells in BM. Up to 40 % of CD3+CD4+ cells in the BM expressed the activated/memory phenotype compared with < or = 10% in the spleen and lymph nodes. Analysis of TCR Vbeta repertoire revealed that expression of Vbeta3 and Vbeta7 genes was increased as much as fourfold in BM compared to the periphery; most of this increase was within the CD44hi T cells. The accumulation of activated/memory T cells and clonotypic expansion(s) was not seen in the BM of germ-free mice, indicating that it reflects the history of the animal's exposure to antigens. Finally, immunization of mice which express a transgenic T cell receptor specific for ovalbumin peptide resulted in appearance of antigen-specific T cells with activated/memory phenotype in the BM.

Animals↗

Age-related changes in antibody repertoire: contribution from T cells.

The immune system of aged mice produces antibodies that are characterized by low affinity, diminished protection against infections and autoreactivity. It has been shown that these antibodies may be encoded by different immunoglobulin V genes and that the mechanism of somatic hypermutation in the V genes is inefficient. Studies on scid mice reconstituted with B and T cells from donors of different ages suggested that both lymphocyte subsets may contribute to the age-related changes in antibody repertoire. With help provided by T cells from young mice, the response to a hapten, nitrophenyl(acetyl), became gradually dominated by B-cell clones that rearranged a particular germline VH gene (V186.2). However, help from the aged T cells resulted in a heterogeneous response of B cells expressing many different V segments. Analysis of discrete foci of primary antibody-forming cells suggested that the aged T-helper cells are unable to govern the normally-occurring competition between the B-cell clones that have different affinities for the hapten. It is proposed that a signaling disequilibrium from the aged T cells, which provide less efficient help in quantitative terms, supports the growth of low-affinity B cells. This process may be exacerbated due to the apparent hyperactivity of aged B cells to CD40-mediated mitogenic signal.

Aging↗

Trail odors: recognition by insects parasitic on cocoons.

Female parasitic insects in the genera Pleolophus, Endasys, and Mastrus (Hymenoptera: Ichneumonidae) search the ground cover for hosts and avoid areas they have already inspected. Females respond to their own trail odor, and recognition occurs also between conspecific, congeneric, and intergeneric individuals. This is the first direct evidence for recognition between parasitoids at sites other than on the host itself, and between females of different species.

Animals↗