1. Allo-Hematopoietic Stem Cell Transplantation
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2. Allo-Hematopoietic Stem Cell Transplantation ----Allo-HSCT
Graft-versus-Host Disease(GVHD)
GVHD: a disease occuring in bone marrow transplant recipients that is caused by the reaction of mature T cells in the marrow graft with alloantigens on host cells. The diease most often affects the skin, liver, and intestines.
Theory of Cytokine Storm
Functions of cells in GVHD
T cells
NK cells
Hematopoietic microenvironment(造血微环境)
Progress of Allo-HSCT

3. Theory of Cytokine Storm
Damage of tissue in pretreatment
host's MHC protein↑ → donor's immunocytes recognize host cells↑
Activation and proliferation of donor's T lymphocytes
Cells and inflammatory factors attack target tissue leading to GVHD

4. Tissue damage
The spread of cytokin caused by pretreatment or inflammation. Donor immune cells have better distinguishment on receptor MHC.

6. Activation and proliferation of donor T lymohocyte

7. Cell and inflammatory factor attack target cell
monocyte/neutrophil secret inflammatory factor＋CTL →damage totarget tissue and apoptosis.

8. NK cells KIR- Killer immunoglobin-like receptor KIR bind with MHC-I
KIR mismatching:The recipient cell lacks “correct” MHC-I molecules, fails to offer inhibiting signal to donor KIR.

9. Immune Environment of Allo-HSCT
Hematopoietic microenvironment consists of a group of histocytes and matrix. And it can preserve and regulate the local tissue microenvironment of HSC through cell-cell contact and signal molecules. And its functional unit called niche(龛)

10. Bone marrow
Bone marrow is the first and second class immune organ. It has many kinds of immune cells including T lymphocyte, B lymphocyte, NK and DC. These cells and the cytokin they secret and the signaling pathway the mediate form the immune niche

11. Positive effects Effects of Immune Microenvironment
Immune cells provide immunological barrier for regulation of HSC homeostasis and HSC proliferation and differentiation.

12. Positive effects
Promote the homing of stem cells, have great influance on the differentiation from CMP（髓系共同祖细胞) to MEP（巨核／红系祖细胞).

13. Negative effects
If the microenvironment is abnormal, it cannot provide signals for HSC self-renew and differentiation, which leads to the afunction of CD34+ cells.
It protect HSC LSC at the same time, which contributes to the immunological escape of leukaemic cells.

14. Progress of Allo-HSCT Transplantation
Use of immunosuppressant:
MTX（甲氨蝶呤), CsA（环孢素) etc.
Mesenchymal stem cell transplantation at
early stage.
Build chimaera to induce immune tolerance.

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