Since chance of rejection is very high in transplantation between genetically distinct individuals, transplantation is restricted to the donors of same species i.e. allograft.

The rejection of allograft also very common due to incompatibility of MHC antigens, but the rate of rejection is different in different cases.

Depending upon the percentage of match between donor and recipient, the rejection may be acute rejection, or Hyper acute rejection or insidious rejection.

Accute Rejection

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Acute rejection is due to stimulation of T lymphocytes and cell mediated immunity, it takes place subsequent to the establishment of blood vessel communication between recipient and implant. This kind of rejection is known as “early acute rejection reaction”.

If the recipient’s immune system is suppressed with certain suppressive drugs, development of Abs against graft antigens takes place in due course time. Interaction of antibodies with the grafts antigens, results in the formation of immune complexes, followed by complement fixation and finally rejection of the graft.

As this reaction is taking place after some time it is referred as “late acute rejection reactions”.

Hyper Acute Rejection:

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If antibodies for graft cells are already present in the host body rejection takes place very quickly, this quick rejection of graft is known as “Hyper acute rejection”.

Pre existence of antibodies in host is due to pre sensitization through previous pregnancies, or blood transfusion or through previous grafts.

Insidious Rejection:

Deposition of immune complexes on graft tissue leads to slow, silent and unexpressed or secret rejection of the graft. This silent rejection of graft is known as “insidious rejection”.

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Irrespective to the type of rejection, the mechanism of rejection involves sensitized T cells and NK cells in the first set of reactions. Abs are believed to play an important role in chronic rejection.

Hence the mechanism of graft rejection can be divided into first set and second set reactions.

1. First Set Reactions:

Sensitization is the first step in these rejection reactions. Once the graft tissue is vascularized, the graft antigens travel to the lymph nodes through circulation and activate T Lymphocytes.

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Time required for T cell stimulation depends on the time taken for vascularization of the graft. For example rejection reactions take place very quickly in organ transplants, but delayed in skin grafts.

In skin graft vascularization takes place in few days, but in case of organ graft, vascularization is established during the surgical process through direct anstomoses (connection of two structures), allowing passage of graft antigens to the lymph nodes, and activation of T cells.

When T lymphocytes are activated they proliferate to give clones of cells. TC cells enter in to the circulation and reach the graft to destroy the implant tissue through cell-to-cell toxicity.

Remaining T cells in the lymph nodes mobilize phagocytic leucocytes to the graft through their lymphokines. Since capillaries and vessels are composed of a single endothelial cell layer, the first sign of damage at the tissue level is seen in them.

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Damage of blood vessels results intravascular thrombosis, ischemia, hemorrhage, and blood coagulation. Histologically the reactions bear a resemblance to delayed type hyper sensitive reactions.

2. Second Set Reactions:

The second set reaction can be compared to the secondary immune response to an antigen. It takes place when transplantation is repeated for the second time.

Initially graft rejection reaction is brought abut by Tc cells, later Abs and NK cell involve in the reactions, hence in the second set reactions B cell are Important.

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Since the immune system is sensitized through previous graft and immune components are ready in the circulation, rejection of graft cells takes place soon after the establishment of circulation between host and graft.

Infiltration of neutrophils, macrophages, and Tc cells to the site of inflammation serves to provide backup mechanism and ensure rapid and irreversible reactions. As the reactions are so quick vascularization does not take place and the graft tissue becomes pale yellow or whitish due to failure in blood supply.

Hence the rejection of this whitish graft is referred as “white graft rejection”.

The second set reactions are considered as hyper acute rejections reactions due to its rapid action. Second set reaction or hyper acute rejection can be seen rarely in the first attempt of transplantation.

Repeated blood transfusions, or pregnancies, may root generation of Abs for foreign antigens; cross reactivity of this Abs may induce second set reactions even in first attempt of transplantation.

Study of this kind of rejection reaction suggests that there is a possibility of generation of sensitized cells and antibodies for allogenic antigens even in the absence of any graft. The basis for undiagnosed recurrent abortions in some women may be the same.

Since MHC genes are co dominant in nature, fetus expresses both maternal and paternal antigens. If a woman carries Abs against her husbands

Ags, the fetus with paternal antigens may face the graft rejection reaction; as a result the women undergo recurrent abortions.

Whether it is a first set or second set reaction, the degree and type of immunological response varies with the type of transplant.

In spite of mismatch certain grafts such as cornea, cartilage, brain cells etc., may be tolerated. This is due to their presence in privileged sites, where they do not encounter the cells of immune system. In certain rare conditions like bone marrow transfusion the graft assault the host, this kind of reactions is referred as “graft-versus-host reactions”.

Graft versus Host Reactions (G.V.H.)

In certain cases especially in bone marrow transplantation (normally carried in leukemia cases) recipients lymphocytes are destroyed prior to transplantation through irradiation, to prevent the graft rejection reactions.

However the grafted bone marrow with its own lymphocytes perceives the host cells as foreign and starts destroying the recipient’s cells. This kind of grafts reactions are referred as “graft-versus-host reactions” to highlight the problems raised by graft.

GVH reactions are not limited to bone marrow transplants; similar reactions can arise in other tissue or organ transplants. Study of G.V.H. reactions suggests that the G.V.H. reactions increase with age, because of latent infections such as viral, protozoan etc. If immune system of an aged recipient is suppressed prior to transplantation, the patient lost control over organisms of latent infection, and the organisms express their Ags in the absence of host resistance.

The pathogen Ags can induce T cells of the graft, while reacting with pathogen Ags some of the graft T cells get sensitized to recipient Ags and carry GVH reactions.