Browsing by Subject "immune response"
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Item A Review of Dendritic Cell Vaccines in Cancer Treatment and a Managerial Focus on Issues Related to Subject Recruitment(2006-12-01) McFarlin, Tory; Arredondo, LaChelle; Gwirtz, Patricia A.; Oglesby, MichaelMcFarlin, Tory. A Review of Dendritic Cell Vaccines in Cancer Treatment and a Managerial Focus on Issues Related to Subject Recruitment. Master of Science (Clinical Research Management), December 2006, 97 pp., 5 tables, bibliography, 24 titles. Melanoma is form of skin cancer that can become deadly if the cancer progresses to a stage of metastasis. Five year survival rates as low as 10% may be noted in such patients. Decarbazine and Proleukin have been approved by the FDA for the treatment of metastatic melanoma; however both have response rates of approximately 20% or less. New treatment modalities including dendritic cell (DC) vaccines are currently being tested for treating metastatic melanoma with greater safety and efficacy profiles. DC vaccines are made by obtaining a subject’s DCs, priming them with melanoma antigen ex vivo and then injecting them into the patient to initiate an immune response against melanoma tumor cells in vivo. Investigational new treatments such has the DC vaccine must first be tested in clinical trials on research subjects. Subject enrollment issues regarding such a trial can cause delays in advances of the treatment. As an intern with a DC vaccine clinical trial, the author assisted in screening 45 patients and observed many hindrances involving enrollment of subjects. Such hindrances include: low rates of study personnel retention, small patient pools, and competing trials. Recommendations to improve enrollment include: more effective advertisement strategies and increased patient education.Item Intermittent Hypoxic Preconditioning: A Potential New Powerful Strategy for COVID-19 Rehabilitation(Frontiers Media S.A., 2021-04-30) Cai, Ming; Chen, Xuan; Shan, Jieling; Yang, Ruoyu; Guo, Qi; Bi, Xia; Xu, Ping; Shi, Xiangrong; Chu, Lixi; Wang, LiyanCOVID-19 is a highly infectious respiratory virus, which can proliferate by invading the ACE2 receptor of host cells. Clinical studies have found that the virus can cause dyspnea, pneumonia and other cardiopulmonary system damage. In severe cases, it can lead to respiratory failure and even death. Although there are currently no effective drugs or vaccines for the prevention and treatment of COVID-19, the patient's prognosis recovery can be effectively improved by ameliorating the dysfunction of the respiratory system, cardiovascular systems, and immune function. Intermittent hypoxic preconditioning (IHP) as a new non-drug treatment has been applied in the clinical and rehabilitative practice for treating chronic obstructive pulmonary disease (COPD), diabetes, coronary heart disease, heart failure, hypertension, and other diseases. Many clinical studies have confirmed that IHP can improve the cardiopulmonary function of patients and increase the cardiorespiratory fitness and the tolerance of tissues and organs to ischemia. This article introduces the physiological and biochemical functions of IHP and proposes the potential application plan of IHP for the rehabilitation of patients with COVID-19, so as to provide a better prognosis for patients and speed up the recovery of the disease. The aim of this narrative review is to propose possible causes and pathophysiology of COVID-19 based on the mechanisms of the oxidative stress, inflammation, and immune response, and to provide a new, safe and efficacious strategy for the better rehabilitation from COVID-19.Item Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses(MDPI, 2023-02-26) Donkor, Michael; Choe, Jamie Y.; Reid, Danielle; Quinn, Byron; Pulse, Mark; Ranjan, Amalendu P.; Chaudhary, Pankaj; Jones, Harlan P.Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)-nasal nano-vaccine-significantly reduced lung colonization by intravenous challenge of an extra-pulmonary tumor. Protection against tumor-cell lung colonization was linked to the induction of localized mucosal-associated effector and resident memory T cells as well as increased bronchiolar alveolar lavage-fluid IgA and serum IgG antibody responses. The nasal nano-vaccine-induced T-cell-mediated antitumor mucosal immune response was shown to increase tumor-specific production of IFN-gamma and granzyme B by lung-derived CD8(+) T cells. These findings demonstrate that our engineered nasal nano-vaccine has the potential to be used as a prophylactic approach prior to the seeding of tumors in the lungs, and thereby prevent overt lung metastases from existing extra pulmonary tumors.Item T-Helper Cell Responses in Lungs After Immunization and Chronic Respiratory Disease; And Their Association With Pulmonary Inflammation(2001-05-01) Jones, Harlan P.; Simecka, Jerry; Dimitrijevich, S. Dan; Goldfarb, Ronald H.The purpose of these studies was to characterize T helper cell responses in the lungs of mice after immunization and chronic respiratory infection. CD4+ T cells were the major population of T cells resident in the lung in comparison to CD8+ T cells. Polyclonal activation of resident CD4+T cells produced abundant levels of IL-4 in comparison to IFN-γ, indicating that Th2 cells were the major sub-population of CD4+ T cells. In contrast, resident CD8+ T cells were the sole producer of IFN-γ by naïve T lymphocytes. Furthermore, the distribution of T cells was similar between BALB/c, C3H/HeN, C57BL/6 and DBA/2N strains of mice. However differences in the distribution of CD8+T cells, as well as the levels of IL-4 and IFN-y production produced by resident T cells were found between C57 and the other strains of mice tested. These results demonstrate that host genetic factors may be involved in determining host susceptibility to respiratory disease. Differences in the intensity of antigenic stimulation provoke changes in the type of T cell response generated. Intranasal immunization with influenza (FLU) vaccine antigen alone initiated solely an antigen-specific Th2-like response. In contrast, the addition of the potent mucosal adjuvant cholera toxin (CT) in combination with FLU antigen induced not only resident Th2 responses, but also induced antigen-specific Th1-like responses. This change corresponded with a dramatic increase in the number of CD4+ T cells in the lung. Thus, intense immunization of respiratory T cells enhanced resident T helper cell responses, but also promoted the activation of Th1 responses. Chronic respiratory infection also elicited changes in the resident population of T cells consistent with pulmonary inflammatory immune responses. At early stages of infection, CD4+, but not CD8+ T cells increased in number within inductive respiratory lymphoid tissues (lower respiratory nodes [LRNs]). Between day 7 and 14 however, there was a dramatic increase in the number of CD4+ T cells in the lung. Interestingly, CD8+ T cells also increased in the lungs, suggesting their activation along mucosal sites during mycoplasma infection. Mycoplasma-specific IL-4 and IFN-γ production also increased in a tissue-specific/time-dependent manner. IL-4 production was initially observed in the LRNs, whereas significant levels of IL-4 and IFN-γ was produced in both tissues 14 days after infection. In comparison, IFN-γ was the predominate cytokine, produce at 14 days coinciding with pulmonary inflammation. Suggesting that intense activation promoted changes in the resident pulmonary Th2 environment, and possible is a major component of pulmonary inflammatory immune responses. Both CD4+ and CD8= T cells were shown to have a role in modulation of disease severity during mycoplasma disease. Observation of gross pulmonary lesions reveal that mycoplasma infected mice treated with anti-CD8 antibody showed increase clinical signs of disease and pronounced gross pulmonary lesions. Additionally the number of total mononuclear cells increased dramatically in the absence of CD8+ T cells. Thus, CD8+ T cells may have a regulatory role in controlling resident CD4+ T cells that increased 14 days after infection. Chemokine production is known to mediate the recruitment of lymphocytes to enhance the initiation of immunity as well as be responsible for modulating inflammatory responses. We find that mycoplasma increase the number of dendritic cells in the lung 14 days after infection, and stimulated the production of dendritic cell-derived ABCD-1 chemokine. Also, β-chemokine MIP-1α and MIB-1β production was observed during intense immunization as well as during mycoplasma infection. These results provide evidence for a potential mechanism through which changes in resident pulmonary T cell responses occur given the intensity of the immune response generated.Item Toll-like Receptor 2 Mediates the Host's Responses in Murine Respiratory Mycoplasmosis(2008-04-01) Love, Wees JaMar; Jerry W. Simecka; Duncan C. Krause; Stephen R. GrantLove, Wees J., The role of Toll-like receptor 2 in mediating the host’s defenses toward mycoplasma infection in the upper and lower respiratory tracts. Doctor of Philosophy (Microbiology and Immunology), April, 2008, 88 pp., 7 illustrations, bibliography, 144 titles. The purpose of these studies was to investigate the toll-like receptors (TLR) responsible for the recognition of invading mycoplasmas. They were also meant to evaluate the role of Toll-like receptors in the generation of immune responses and disease progression in mycoplasma respiratory disease. To determine the role of TLRs in recognizing viable Mycoplasma pulmonis, we utilized human embryonic kidney (HEK) cell lines that are known to have low basal expression of TLRs. The HEK cell lines used were stably transfected to express various combinations of TLRs. The HEK cell lines used were stably transfected to express various combinations of TLRs including TLR1, 2 and 6. The current paradigm of TLR recognition of mycoplasma is that TLR2 dimerizes with either TLR1 or TLR6 to recognize different subclasses of mycoplasma lipoproteins. However, the recognition of viable M. pulmonis organisms remains unclear. When stimulated with viable M. pulmonis, it was discovered that TLR2 was pivotal in mediating the host’s pro-inflammatory cytokine production and that the co-expression of TLR1 or TLR6 enhanced the response. To study their role in mycoplasma recognition and disease progression, we utilized TLR2 knockout (KO) mice. Bone-marrow derived dendritic cells (BMDC) from TLR2 KO mice showed an impaired ability to produce pro-inflammatory cytokines such as IL-12p40 in response to viable M. pulmonis. In addition, the host’s ability to clear the infection was also impaired in TLR2 KO animals. There were higher numbers of cfu in the lower respiratory tract where alveolar macrophages are known to mediate the host’s intrapulmonary clearance of organism. In the upper respiratory tract, where alveolar macrophages (AM) are absent, the production of anti-microbial peptides (e.g. β defensing) in response to TLR2 agonists has been demonstrated. Thus, TLR2 does mediate the host’s immune response to mycoplasma infection, by interfering with the host’s ability to clear the infection and be interfering with the host’s ability to mount an effective inflammatory response. These results also suggest that the TLR2 mediated anti-mycoplasma effects vary and are compartmentalized along the respiratory tract. These studies demonstrated diverse and novel roles of TLRs in respiratory infections and will serve as a platform for future studies investigating mycoplasma respiratory infections.