Transplantation: Meaning, Types and Mechanism

In this article we will discuss about Transplantation:- 1. Meaning of Transplantation 2. Types of Transplant 3. Mechanism of Transplant Rejection 4. Tissue Typing 5. Prevention of Graft Rejection. 

Contents:

1. Meaning of Transplantation
2. Types of Transplant
3. Mechanism of Transplant Rejection
4. Tissue Typing
5. Prevention of Graft Rejection

1. Meaning of Transplantation:

Transplantation is a useful procedure in surgical repair or replacement of diseased tissues or organs. It has been well-established that an animal accepts grafts of its own tissue or that of an identical twin, while a graft from another animal of the same species is rejected. The immune response induced by the transplantation (HLA) antigens present in all mammalian cells is the reason for the rejection of exogenous grafts.

The first record of plastic surgery is found in Sushrut Sanhita (800 BC). The first Indian surgeon Sushruta reconstructed a severed nose of a patient with the patient’s own skin flap.

Transplantation may be fresh organs or stored organs in orthotropic grafts, the transplant is applied in anastomosed normal site (e.g. skin graft), whereas heterotopic grafts are placed in anatomically abnormal sites (e.g.. thyroid transplanted in subcutaneous tissue).

2. Types of Transplant:

1. Auto-graft (Autogenic graft). It is a tissue of one site engrafted to another site in the same individual.

2. Isograft (Syngenetic graft). It is a graft placed in another individual of the same genetic constitution (e.g. monozygous twins or members of inbred strains).

3. Allograft (Homograft or allogeneic graft). It is a graft transfer between two genetically different members of the same species.

4. Xeno graft (Xenogeneic graft). Grafts between members of different species are called xeno-graft. It was formerly known as heterograft.

Auto-graft and isograft are usually accepted and survives causing a minimum inflammatory reaction. Allografts and xenografts usually undergo necrosis and are rejected due to genetic and antigenic incompatibility.

Allograft Reaction:

Rejection of the graft by recipient is called allograft reaction. The most successful organ transplant is that of kidney. Other organ transplants such as bone marrow has been tried but with little success.

3. Mechanism of Transplant Rejection:

Changes observed in human renal allograft rejection is almost similar to that observed in mice:

1. The graft becomes vascularized within a few days and appears to be accepted initially.

2. Between 3-9 days, there is increasing infiltration of the graft by lymphocytes and monocytes with marked reduction in circulation. At this stage, very few plasma cells invade the graft.

3. Between 10-11 days, the necrosis begins to be visible to the naked eye.

4. On 12th or 13th day, the graft sloughs off completely.

Cell mediated reaction is almost responsible for the rejection. Rejection is brought by helper T cells which activate cytotoxic T cells, macrophages and B cells when second allograft from the same donor is applied on a sensitized recipient, it will be rejected in 5-6 days. In this accelerated rejection of second graft second set reaction, antibodies play an important role along with cell-mediated immunity.

Antibodies are formed abundantly from the 11th day onward of transplantation. Thus a graft is rejected either by sensitized T cells or by circulating antibodies. Antibody induces platelet aggregation or type II hypersensitivity reaction (ADCC), Antibody Dependent cell mediated cytotoxicity.

4. Tissue Typing and Matching in Transplantation:

ABO compatibility is essential in all tissue transplantation. Survival of an allograft depends on HLA compatibility. HLA antigens are expressed on the surface of leucocytes (especially lymphoid cells). A full HLA type of an individual contains two haplotypes (haplotype—one strand of chromosome pair), inherited from each parent.

There is reasonable opportunity for genetic matching of siblings of a patient, 25% chance for both haplotypes and 50% chance of one haplotype. With many HLA antigens discovered, there is possibility of thousand halo-types. There is a remote chance that two random individuals will have completely identical haplotypes. The best HLA compatible donors are selected from the family members.

i. Leucocytes Grouping:

The HLA antigens of class I type on leucocytes are identified by sera obtained from:

(i) Multiparous women who usually possess antibodies to HLA antigens of their husbands

(ii) Recipient of multiple blood transfusion

(iii) Volunteers who are repeatedly skin grafted

(iv) Monoclonal antibodies prepared against HLA antigens.

Cytotoxic Test:

A purified suspension of blood lymphocytes of donor is mixed with the recipient’s serum and a panel of standard sera for HLA antigens in presence of complement. When lymphocytes carry the appropriate antigens, the cytotoxic antiserum will combine with the lymphocytes (target cell).

The antigen-antibody complex will activate the complement and damage the cell membrane and the permeability of cell membrane is increased and the same is detected by dye (trypan blue) uptake into the cell, i.e. the dead cells are stained by the dye.

ii. Mixed Leucocyte Culture Test:

The test detects class II antigens of HLA complex and cell mediated immunity. Lymphocytes from both donors and recipients are cultured together (co-cultivation). The test is based on the principle that T-lymphocytes—when exposed to incompatible HLA antigen—undergo blastoid transformation, take up thymidine and divide.

iii. Lymphocyte Transfer Test:

Peripheral blood lymphocytes of recipient is injected intradermally into several prospective donors. Delayed hypersensitivity reaction at the injection site is indicative of immune response of recipient leucocytes against the donor tissue. Persons showing no response against recipient’s leucocytes is chosen as donor.

iv. Detection of Preformed Antibody:

Donor’s lymphocytes are matched with recipient’s serum. If preformed antibodies are present in patient’s serum, the lymphocytes of the donor undergo lysis.

5. Prevention of Graft Rejection in Transplantation:

1. Immunosuppression:

When HLA typing of the recipient and donor is well-matched, a state of immuno-suppression is produced in the recipient so that the transplant tissue survives for a long time. By irradiation, corticosteroids and anti-lymphocytic serum (ALS) the immunological reactivity may be non-specifically depressed. Such patients are susceptible to infections and prone to development of lymphomas.

2. Transplantation in Anatomically Protected Sites:

There are certain anatomically protected sites where allografts are permitted to survive, e.g. cornea, cartilage and testicle grafting. The avascularity of cornea limits the entry of lymphocytes into the graft.

3. Immunological Enhancement:

The circulating antibody produced against graft antigens can—under circumstances—protect the graft from cell mediated immune response. This phenomenon is known as “Immunological enhancement“. If the recipient animal is previously immunized with one or more injections of tissue from the prospective donor and transplant applied subsequently, the transplant survives for longer duration.

Following transplantation of kidney in rats by this method, the graft maintains normal function for a year or more. The immunological enhancement phenomenon can be passively transferred from immunized animal to a normal animal. In certain human kidney transplantations, the method has been used with some success.