Transplantation or grafting of organs and tissues is a common medical procedure emerged in early 1970s. Although it is life giving, but it carry the risk of damage and the bulk of damage that occur in graft rejections can be attributed to expression of cytotoxic T-cells and other killer cells.

The bases for graft rejection:
In general, the genes and receptors in MHC classes I and II are extremely important in recognizing self and in regulating the immune response. The pattern of MHC genes can be similar in related siblings, but the more is that the relationship, the less likely that MHC genes and receptors will be similar when donor tissue (a graft) displays surface receptors of a different MHC class, the T-cells of the recipient (called the host) will recognize its foreignness and they release IL
2
this stimulus amplifies helper and cytotoxic T-cell specific & the foreign Ags on the donated cells. The cytotoxic cells bind to grafted tissue and secrete lymphokines that begin rejection process within 2weeks of transplantation. Late in this process Abs formed against the graft tissue contribute to immune damage. Finally the destruction of the vascular supply promoting death of the grafted tissue.
Classes of grafts:
Grafts are generally classified according the genetic relationship between the donor and the recipient:

Autograft

tissue transplanted for one site on an individual’s body to another site or his body skin replacement in burn repair.

Isograft

tissue from an identical twin.

Allografts

the most common type of grafts, are exchanges between genetically different individuals belonging to the same species (two human).

Xenograft

is a tissue exchange between individuals of different species.

Donor-Recipient matching
ABO matching must be done
ABO incompatibility contraindicate the transplantation, overcome by removal of anti-A or anti-B isohemagglutinin from recipient.
HLA matching done routinely, but the clinical significance depend on the organ to be transplant

In kidney there is correlation between the common HLA and the survival rate.

In bone marrow, it is very important to avoid (GVHD)

tested by mixing culture of recipient lymphocyte with lymphocyte from donor

should react minimally to each other (MLR).

It is not significant for liver transplantation the same for heart, lung and bowel.
Screening of the recipient serum for cytotoxic antibodies directed against the donor lymphocyte (observing the lyses of donor lymphocytes by the recipient serum plus complement- cross matching)

Graft rejection
It is a consequence of an immune response mounted by the recipient against the graft due to incompatibility. Rejection episodes classified according to time between transplant and start of episodes:
1.
Hyper acute rejection (early rejection)
2.
Acute rejection
3.
Chronic rejection

Hyperacute rejection: within minutes due to

pre-existing Ab

Activation of complement system

chemotactic attraction triggering the inflammatory cascades

or by ADCC.
This is usually irreversible and avoided by proper matching.
The transplant must be immediately removed.

Acute rejection
If occur within few days

secondary immune response.
If occur beyond 1 st week

primary immune response mediated by CD8 + , CD4 & Thl
Can be reversed by increasing immunosuppressive agents.

Chronic rejection
Insidiously progressive loss of function of grafted organ due to non-immune (prolonged use of immunosuppresion or due to vascular endothelial injury).
Poor immune responses against transplanted tissue associated with fibrosis of internal blood vessels.

Graft versus host disease (GVHD)
In sever ID, the host cannot reject a graft, but graft incompatibility is a two-way phenomenon. Some grafted tissues (especially bone marrow) contain indigenous population (passenger lymphocytes) which attack and destroy recipient’s cells.
The 3 components for GVHD:
Graft immune competent T-cells.
Immune compromised recipient.
The recipient must express Ags foreign to the donor.
GVHD can be reduced by treating the donor tissue with antithymocyte globulin or monoclonal Ab before grafting to eliminate mature T-cells from the graft.
Types of transplants
Transplantation surgery has been performed on every major organ including parts of the brain.
The most frequent transplant operations include skin, heart, kidney, coronary artery, cornea and bone marrow.
The source of organs and tissues are
Live donors (kidney, skin, bone, marrow, liver).
Cadavers (heart, kidney, corneal, and fetal tissues as fetal pancreas in DM or fetal brain in parkinson disease, and parent liver, lobe of lung).
Recent advances made it possible to isolate stem cell directly for the blood of the donors without bone marrow sampling.

Immunosuppressive drugs
Drugs that suppress allograft rejection & prolong immunosuppression, greatly enhances the recipient’s susceptibility to opportunistic infections and neoplasms in addition to bone marrow suppression and neutropenia.
Corticosteroids (Prednisolone)
Inhibitors of signal transduction (Cyclosporin A)
Which is a polypeptide isolated from fungus, interfere with release of IL
2 and block activation of T-cells it also reduce incidence of fatal infections what makes this drug so valuable is that it does not inhibit important lymphoid cells & phagocytes and its adverse is kidney toxicity &

BP.
Used in treatment of DM
-1
& RA.
Some antimetabolites (Azathioprine) which block DNA synthesis.
Polyclonal Ab (anti-T-cell Ab) (anti-thymocyte globulin).
Monoclonal Ab. (anti CD3 [OKT
3
]) (anti-IL
2
receptors) those with a lesser side effects.