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Mathematical models of the activation and regulation of the immune system.

机译：免疫系统激活和调节的数学模型。

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摘要

We develop models of immune dynamics based on systems of delay differential equations, systems of difference equations, and systems of partial differential equations. Our models focus on the dynamics of the immune response to chronic myelogenous leukemia (CML) and immune regulation during a primary immune response.;The first part of the thesis analyzes immune dynamics after a CML patient receives a stem cell transplant. This model studies the interactions between the immune cell populations from the patient and the donor stem cells. We observe that a successful transplant results from a blood-restricted graft versus host response, in which donor immune cells attack and destroy all the patient's blood cells. We hypothesize that a high population of general, non-leukemic host blood cells prior to transplantation favors a successful outcome.;The second part of the thesis considers a combining the biological drug Gleevec with cancer vaccinations as a treatment for CML. The model is based on experimental data showing that most CML patients exhibit brief anti-leukemia immune responses during the course of Gleevec treatment. We hypothesize that these brief immune responses can be magnified via cancer vaccines to lead to a robust anti-leukemia immune response.;The third part of the thesis develops a model that involves several aspects of the adaptive immune response, including antigen presenting cells, helper and killer T cells, and regulatory T cells. The model studies the dynamics of self/non-self discrimination and immune regulation. We hypothesize that the immune system contains a population of naturally-occurring regulatory T cells that are primarily reactive to foreign antigen. These regulatory cells modulate the strength of the primary immune response during an infection.
机译：我们基于时滞微分方程系统，差分方程系统和偏微分方程系统开发免疫动力学模型。我们的模型侧重于对原发性免疫反应期间慢性粒细胞白血病（CML）的免疫反应的动力学和免疫调节。论文的第一部分分析了CML患者接受干细胞移植后的免疫动力学。该模型研究了患者免疫细胞群与供体干细胞之间的相互作用。我们观察到成功的移植是由血液受限的移植物抗宿主反应产生的，其中供体免疫细胞攻击并破坏了患者的所有血细胞。我们假设移植前大量的普通非白血病宿主血细胞有利于成功的结果。本文的第二部分考虑了将生物药物格列卫与癌症疫苗相结合作为CML的治疗方法。该模型基于实验数据，表明大多数CML患者在格列卫治疗期间表现出短暂的抗白血病免疫反应。我们假设可以通过癌症疫苗将这些短暂的免疫反应放大，从而产生强大的抗白血病免疫反应。论文的第三部分建立了一个模型，该模型涉及适应性免疫反应的多个方面，包括抗原呈递细胞，辅助细胞和杀伤性T细胞，以及调节性T细胞。该模型研究了自我/非自我歧视和免疫调节的动力学。我们假设免疫系统包含一群天然存在的调节性T细胞，这些细胞主要对外源抗原起反应。这些调节细胞在感染过程中调节初次免疫反应的强度。

著录项

  • 作者

    Kim, Peter S.;

  • 作者单位

    Stanford University.;

  • 授予单位 Stanford University.;
  • 学科 Mathematics.;Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 315 p.
  • 总页数 315
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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