Thesis (Ph. D.)--University of Wisconsin--Madison, 1976. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Bibliography: leaves 236-244.

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 44-48).

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 35-38).

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 45-51).

Thesis (M.S.)--University of Wisconsin -- Madison, 1956. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

No description available.

The Rhesus (Rh) D antigen is important in transfusion medicine and is the major target in haemolytic disease of the newborn (HDN). The aims of this project were to characterise the helper-T (Th) cell response that drives anti-D alloantibody production in HDN as a first step towards developing an improved or alternative strategy to the current programme of prophylaxis, based on the manipulation the T-cell response. Peripheral blood mononuclear cells (PBMC) were obtained from 22 individuals, who had developed anti-RhD alloantibodies following natural or deliberate immunisation, and from 22 RhD negative and from 12 RhD positive control donors who had not been immunised with RhD. A panel of 69 overlapping synthetic 15-mer peptides, spanning the sequence of the RhD protein, was screed for the ability to stimulate recall proliferation and cytokine production from T-cells in cultures of the PBMC. T cells from all 22 of the alloimmunised donors proliferated in response to RhD peptides and typically multiple peptides were stimulatory. In contrast, only a few minor responses were observed in the control donors. RhD peptides 6, 13, 17, and 28 were identified as immunodominant peptides that stimulated proliferation in over 50% of the alloimmunised donors. Each of these peptides were promiscuous in their ability to stimulate T-cells from donors of the common HLA allotypes in this study. Each immunodominant peptide contains multiple core epitopes and multiple sets of MHC/TCR contacts. Preliminary findings indicate that neither peptides shorter than 15mer length nor analogues can be designed to boost or tolerise alloimmunised donors. The RhD peptides induced a complex pattern of cytokine production from alloreactive T cells. Both IFN-gamma and IL-4 could be produced to the RhD peptides indicative of a Th0 response. In addition, particular peptides elicited the production of the potentially inhibitory cytokines IL-10 or TGFb and not proliferation.

archives@tulane.edu / Neutrophils are the most abundant white blood cells in human blood and require continuous replenishment from bone marrow granulopoiesis throughout life. Their function as phagocytes in innate immunity has been well studied, but the dynamics and movement of neutrophils in vivo are less clearly understood. To quantitate the kinetics of neutrophil movement during homeostasis, acute inflammation, and aging, we applied 5-bromo-2'-deoxyuridine (BrdU) pulse-chase labeling followed by hematology and flow cytometry analyses in healthy, acutely-infected, and aged rhesus macaques (Macaca mulatta). We applied our kinetics results to a mathematical model and calculated that neutrophils have a half-life of 1.63 ± 0.16 days and a daily production of 1.42×109 cells / L / day in heathy young adult rhesus macaques. In rhesus macaques undergoing acute inflammation, we followed neutrophil kinetics during acute stages of a bacterial infection (Shigella) and viral infection (SIV). A massive replenishment of neutrophils from bone marrow to blood as indicated by BrdU kinetics occurred as early as 3 days post Shigella inoculation, the degree to which correlated with the Shigella inoculation doses. As animals aged, neutrophil production declined while plasma G-CSF levels increased, and there was an earlier release, as well as higher in-group variability in neutrophil kinetics, particularly upon reaching 20 years of age or older (equivalent to 70 years or more in humans). This suggested a dysregulated feedback mechanism whereby increased levels of G-CSF failed to restore neutrophil production in elderly rhesus macaques that was associated with induced production of pro-inflammatory cytokines and earlier release of less mature neutrophils and PMN-MDSCs. Taken together, we established a rhesus macaque model to study neutrophil kinetics and functions in vivo during homeostasis, acute inflammation, and aging. Our results emphasized the massive production of neutrophils during homeostasis and the continuous requirement but reduced replenishment capabilities during aging. The significance of the results also indicates an important role for these long-discovered leukocytes in maintaining homeostasis beyond phagocytic pathogen clearance. / 1 / Ziyuan He

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.