Regulation of Humoral Immunity to Allogeneic Platelet Transfusion 公开
Gilson, Christopher (2010)
Published
Abstract
Abstract
Regulation of Humoral Immunity to Allogeneic Platelet
Transfusion
By
Christopher R. Gilson
Platelet transfusion is an essential treatment for
thrombocytopenia, which can result
from a wide range of conditions including acute hemorrhage,
hematological malignancies,
hematopoietic stem cell transplantation, and congenital platelet
disorders. A life-saving
therapy, transfusion may also carry significant risks. Anti-donor
antibodies can be
developed and abrogate the efficacy of transfused platelets.
Increasingly sophisticated
methodologies, including leukoreduction and irradiation of platelet
products have decreased
the incidence of anti-donor antibodies by limiting the recipient's
exposure to antigenic white
blood cells. In spite of these efforts, alloimmunization following
platelet transfusion still
occurs in a significant percentage of patients.
Table of Contents
Table of Contents
Chapter 1 - Introduction
..............................................................................................
1
Clinical significance of platelet alloimmunization
................................................... 2
A brief retrospective of transfusion
medicine...........................................................
3
Development of platelet transfusion as a therapeutic modality
................................ 5
General platelet physiology
......................................................................................
6
Clinical platelet storage and transfusion
...................................................................
9
Platelet refractoriness
...............................................................................................
11
Allospecific T cell activation
...................................................................................
12
Humoral response to platelet
transfusion..................................................................
14
Much ado about platelets
.........................................................................................
16
References
......................................................................................................................
18
Chapter 2 - MHC Class II on Transfused Murine Blood is Not
Required for
Alloimmunization Against MHC Class I
....................................................................
33
Abstract
...........................................................................................................................
34
Introduction.....................................................................................................................
35
Materials and methods
....................................................................................................
38
Results
...........................................................................................................................
40
Discussion
.......................................................................................................................
42
References.......................................................................................................................
45
Figure
Legends................................................................................................................
48
Chapter 3 - Characterization and Visualization of the Allogeneic
Platelet
Specific CD4+ T cell Response
.....................................................................................
54
Abstract
...........................................................................................................................
55
Introduction.....................................................................................................................
56
Materials and methods
....................................................................................................
58
Results
...........................................................................................................................
62
Discussion
.......................................................................................................................
66
References.......................................................................................................................
71
Figure
Legends................................................................................................................
78
Chapter 4 - A Novel Mouse Model of Red Blood Cell Storage and
Post-
Transfusion in Vivo Survival
......................................................................................
87
Abstract
...........................................................................................................................
88
Introduction.....................................................................................................................
89
Materials and methods
....................................................................................................
91
Results
............................................................................................................................
95
Discussion
.......................................................................................................................
98
References.......................................................................................................................
102
Figure
Legends................................................................................................................
105
Chapter 5 - Discussion
.................................................................................................
111
Summary
.........................................................................................................................
112
7
Discussion
.......................................................................................................................
115
To leukoreduce or not to
leukoreduce.......................................................................
115
Leukoreduction of platelet units
...............................................................................
116
Modeling platelet isolation and collection in a murine setting
................................. 119
Recipient T cell response to allogeneic platelet transfusion
..................................... 121
Modeling blood component storage in murine
systems............................................ 123
Prevention of platelet alloimmunization
...................................................................
125
Future
Directions.............................................................................................................
128
Short term future directions
......................................................................................
128
Long term future
directions.......................................................................................
131
General conclusions
........................................................................................................
134
References.......................................................................................................................
135
List of Figures
Chapter 2
Figure 2.1
..................................................................................................................
50
Figure 2.2
..................................................................................................................
51
Figure 2.3
..................................................................................................................
52
Figure 2.4
..................................................................................................................
53
Chapter 3
Figure 3.1
..................................................................................................................
82
Figure 3.2
..................................................................................................................
83
Figure 3.3
..................................................................................................................
84
Figure 3.4
..................................................................................................................
85
Figure 3.5
..................................................................................................................
86
Chapter 4
Figure 4.1
..................................................................................................................
107
Figure 4.2
..................................................................................................................
108
Figure 4.3
..................................................................................................................
109
Figure 4.4
..................................................................................................................
110
8
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