Deptt. Of Zoology
Deptt.
R.T.M. Nagpur University, Nagpur
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h untroduction
h u unosuppressive Agents
h u unosuppressive Therapy
h Conclusion
h References
h Transplantation i unology - sequence of events that
occurs after an allograft or xenograft is re oved fro
donor and then transplanted into a recipient.
h Macrophages
h Activated B Cells
h Natural antibodies
h unduced antibodies
3 T cells
4 Other cells ²
h Natural killer cells
h Monocytes/Macrophages
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h CD4+ differentiate into cytokine producing
effector cells
h Da age graft by reactions si ilar to DTH
h CD8+ cells activated by direct pathway kill
nucleated cells in the graft
h CD8+ cells activated by the indirect pathway are
self MHC-
MHC-restricted
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h
'( ), uN ² ü , and TN - are i portant ediators of graft
'(
rejection.
h
'(( * pro otes T-
' T-cell proliferation and generation of T ²
Ly phocytes.
h
+,-- is central to the develop ent of DTH response.
+,
h ,+-- has direct cytotoxic effect on the cells of graft.
,+
h A nu ber of cytokines pro ote graft rejection by inducing
expression of class ² u or class ² uu MHC olecule on graft cell.
h The interferon (ơ, and , TN ² ơ and TN - all increases
class ² u MHC expression, and uN - increases class ² uu MHC
expression as well.
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h Hyperacute Rejection
h Acute Rejection
h Chronic Rejection
h Characterized by thro botic occlusion of the
graft
h Begins within inutes or hours after
anasta osis
h Pre--existing antibodies in the host circulation
Pre
bind to donor endothelial antigens
h Activates Co ple ent Cascade
h Xenograft Response
h Lung
h Liver
'
h irst atte pt in Ñ963 by Hardy and Co - workers.
h irst successful transplantation by Toronto group in Ñ983.
h un conjunction with heart transplantation, to treat diseases such as cystic
fibrosis and e physe a or acute da age to lungs.
h irst year survival rate is about 60%.
h Diseases like diabetes and various type of nephritis can be
elleviated by kidney transplantation.
h Survival rate after one year transplantation is >90%.
'
h ut treat congenital defects and da age fro viral (hepatitis
or che ical agents. (Chronic alcoholis .
h Liver one year survival exceeds 75% and five year is 70%.
h Offers a cure for diabetes ellitus.
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h ut is used to treat burn victi s.
u unosuppression can be brought about by 3
different ways :-
:-
h Surgicalablation
h Total Ly phoid urradiation
hu unosuppressive drugs
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Monoclonal antibodies
h To suppress the activity of subpopulation of T- T-cells.
h To block co-
co-sti ulatory signals.
h Ab to the CD3 olecule of TCR (T cell receptor co plex results in a rapid
depletion of ature T T--cells fro the circulation.
h Ab specific for the high
high--affinity uL
uL--2 receptor is expressed only on activated
T-cell, blocks proliferation of T-
T-cells activated in response to the alloantigens
of the graft.
h To treat donor·s bone arrow before it is transplanted.
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