Book contents
- Frontmatter
- Contents
- List of Contributors
- Preface
- PART I GENERAL PRINCIPLES
- 1 Historical Aspects of Chronic Graft versus Host Disease
- 2 The Pathophysiology of Acute Graft versus Host Disease
- 3 Pathophysiology of Chronic Graft versus Host Disease
- 4 Animal Models of Chronic Graft versus Host Disease
- 5 Incidence and Trends
- 6 Clinical Manifestations and Natural History
- 7 Risk Factors and Predictive Models for Chronic Graft versus Host Disease
- 8 Biomarkers in Chronic Graft versus Host Disease
- PART II CLINICAL MANAGEMENT
- PART III ORGAN SITE OR SYSTEM-SPECIFIC MANIFESTATIONS
- PART IV SPECIAL CONSIDERATIONS IN CHRONIC GVHD
- Index
- Plate section
2 - The Pathophysiology of Acute Graft versus Host Disease
from PART I - GENERAL PRINCIPLES
Published online by Cambridge University Press: 26 August 2009
- Frontmatter
- Contents
- List of Contributors
- Preface
- PART I GENERAL PRINCIPLES
- 1 Historical Aspects of Chronic Graft versus Host Disease
- 2 The Pathophysiology of Acute Graft versus Host Disease
- 3 Pathophysiology of Chronic Graft versus Host Disease
- 4 Animal Models of Chronic Graft versus Host Disease
- 5 Incidence and Trends
- 6 Clinical Manifestations and Natural History
- 7 Risk Factors and Predictive Models for Chronic Graft versus Host Disease
- 8 Biomarkers in Chronic Graft versus Host Disease
- PART II CLINICAL MANAGEMENT
- PART III ORGAN SITE OR SYSTEM-SPECIFIC MANIFESTATIONS
- PART IV SPECIAL CONSIDERATIONS IN CHRONIC GVHD
- Index
- Plate section
Summary
ACUTE GVHD PATHOPHYSIOLOGY: A THREE-STEP MODEL
Acute graft versus host disease (GVHD) results from complex interactions between donor T cells and host tissues in an inflammatory milieu. The pathophysiology of acute GVHD can be considered as a three-step process involving both the innate and adaptive immune systems (Figure 2.1). GVHD pathophysiology can be summarized in a three-step process. In step 1, the conditioning regimen (irradiation, chemotherapy, or both) leads to the damage and activation of host tissues, especially the intestinal mucosa. This allows the translocation of lipopolysaccharide (LPS) and other inflammatory stimuli from the intestinal lumen to the circulation, stimulating the secretion of the inflammatory cytokines such as tumor necrosis factoralpha (TNF-α) from host tissues. These mediators increase the expression of major histocompatibility complex (MHC) antigens and adhesion molecules on host antigen-presenting cells (APC)s, enhancing the recognition of MHC and minor histocompatibility antigens (mHA) by mature donor T cells. Donor T-cell activation in step 2 is characterized by a predominance of T-helper type 1 subset (Th1) cells and the secretion of interferon-gamma (IFN-γ), which activates mononuclear phagocytes. Regulatory T cells (Treg) limit the proliferation and clonal expansion of activated donor T cells.
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- Chronic Graft Versus Host DiseaseInterdisciplinary Management, pp. 8 - 16Publisher: Cambridge University PressPrint publication year: 2009