Immune Mechanisms of Graft Rejection
The reaction of host against allo-antigens of graft which is also called as host vs graft (HVG)
rejection. This considered as a main obstacle in organ transplantation. The involvement of immune
mechanisms in graft rejection is based on
a) Time of rejection
b) Nature of allo-antigens of graft
c) Immune status of host
According to the time of rejection, the graft rejection can be of following types with distinct
immune mechanisms
1) Hyper acute rejection
2) Accelerated rejection
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3) Acute Rejection
4) Chronic Rejection
Hyper-acute Rejection
This kind of transplant rejection has very quick onset for tissue rejection. It occurs within minutes
to hours. The high titer of pre-formed antibodies against antigens of graft are responsible for such
form of reactions. Antigen/antibody (immune) reaction occurs on the tissue surface. Afterward the
fixation of complement leads towards graft destruction
Accelerated Rejection
This kind of rejection is also called as secondary or 2nd set rejection. It occurs after transplantation
of second graft. It is due to sharing of antigenic determinants with the first transplant. Time
required for this form of rejection is within 2-5 days. The sensitized T-cells during first graft are
responsible for this kind of rejection. Moreover, the Lymphokines and cytotoxic T-lymphocytes
(CTLs) augment it.
Acute Rejection
It is also called as primary or 1st set of tissue rejection. It occurs during first graft with allo-antigen
on grafted tissue. The time span required for such form of rejection is 1-3 weeks. These reactions
are mediated by sensitized T-cells to class I & II of allo-graft. Furthermore the secretion of
Lymphokines leads towards the activation of monocyte and macrophages.
Chronic Rejection
This form of transplantation rejection is called as delayed rejection which occur within months to
years. After transplantation the graft remains normal for months to years but sudden rejection occur
due to still unknown mechanisms. These are many hypotheses reading such form of rejection like
the involvement of various infections which are responsible for loss of immunological tolerance
by grafted tissue in host.
Prevention & Treatment of Graft Rejection
If there is decrease in tissue rejection then there is relative increase in survival of graft. There are
successful grafts occur for example mostly in case of kidney & cornea. For successful
transplantation there is need of better understanding of immune response and MHC
The success of tissue graft is based on following important factors
1) Donor selection
2) Recipient preparation
3) Immunosuppression
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Donor Selection
For appropriate donor selection, there should be MHC compatibility with recipient. Identical twins
are considered as the ideal donor which are also termed as Isograft. HLA matched siblings have
95-100% chance of graft success. One haplotype of parent or sibling must be HLA-D matched for
successful graft. Moreover, ABO compatibility is also essential for high success rate of transplant
Recipient Preparation
For successful tissue graft, the recipient should be in good health with no current infection.
Similarly the absence of active malignancy would also increase the success rate. Moreover, in
recipient the absence of any systemic diseases would lead towards better rehabilitation. Likewise,
the recipient should not be hypertensive. One to five transfusions of 100-200 ml of donor’s blood
at 1-2 weeks interval would also increase the compatibility level with donor.
Immunosuppression
This is the way through which host immune system can be suppressed and is most essential
component of allo-transplantation. For this there is usage of following immunosuppressive drugs
with their specific mode of actions
• Cyclosporin A
It inhibit IL-2 synthesis following antigen exposure to host as a result no immune response is
generated for allo-antigens.
• Rapamycin
It inhibits signal transduction for the activation and differentiation of immune cells. For instance
inhibition of T-cells proliferation and activation is achieved by this.
Transplantation of Blood Cells & Bone Marrow
Clinically, transplantation of blood and bone marrow is used for treating various hematological
disorders. The success of these graft is achieved by having good compatibility between donor
and recipient. For this purpose following procedures are used
1. ABO blood grouping
2. Cross matching
3. HLA typing