COMPONENTS OF IMMUNE SYSTEM INVOLVED IN GRAFT REJECTION:

COMPONENTS OF IMMUNE SYSTEM INVOLVED IN GRAFT REJECTION:

Involvement of T cells-

experimentally , it has been proved that lymphocytes could transfer allograft immunity but serum antibody couldn't. i.e. nude mice which lack a thymus and as a result functional T cells couldn't reject a graft. they even accepted xenografts..
Both CD4+ and CD8+ cells are involved; and experimentally; it was observed that :

       a) removal of only CD8+ had no effect on graft rejection,
       b) removal of only CD4+ cells lead to survival of graft for 15-30 days,
       c) removal of both CD4+ and CD8+ cells lead to survival of graft for upto 60 days.


Among T-helper cells; T helper (1) cells are major contributors.


Involvement of dendritic cells:

Dendritic cells act as APC and present exogenous antigens in context of MHC1 molecule to CD8+ or cytotoxic T cells; thus helping in the recognition of alloantigens as part of the rejection process.
so, inhibiting dendritic cells and thus interfering with the presentation of antigen can help graft acceptance.
besides, pretreatment with donor dendritic cells is also beneficial and has been shown to prolong the acceptance of both head and pancreas transplants in mouse experiments.


Involvement of MHC:

cells tissues that are similar in context of antigens they contain are called histocompatible and transplantation between  histocompatible tissues donot induce immune response whereas the one between histoincompatible tissues does.
Various antigens determining histocompatibility are encoded by more than 40 different loci but the most responsible loci are associated with MHC.
the main reasons for graft rejections are as below:

          a) difference in blood group of donor and acceptor,
          b) relation between major histocompatibility antigens,
          c) relation between minor histocompatibility loci.

TESTS OF COMPATIBILITY BETWEEN DONOR AND ACCEPTOR

Initially, the donor and recipient are tested for blood-group compatibility.
The blood group antigens are expressed on RBC, epithelial cells and endothelial cells.
Antibodies produced to anitgens present on graft induce antibody-mediated complement lysis of the incompatible donor cells.
MHC matching-Hla typing of donor and recipient is accomplished through;

          a) a microcytotoxicity test,
          b) mixed lymphocyte reaction(MLR)

Microcytotoxicity test-

WBC from donor and recipient are distributed into wells on a microtiter plate. Now, the antibodies for various MHC-1 and MHC-2 allele are added to these wells. Now the plate is incubated and complement is added to the wells.
Now, if antigen and antibody form complexes then addition of complement lyse them and the dead cells take up a dye such as trypan blue. This indicates the presence or absence of various MHC alleles and the one from donor and recipient can be matched.


Mixed Lymphocyte Reaction:

MLR is used to quantify the degree of class 2 MHC compatibility between the donor and the recipient.
lymphocytes from the donor is irradiated or treated with mitomycin C. It serves as antigen or stimulator cells and lymphocytes from recipient proliferate in response to this. Higher the proliferation, more is the difference between donor and recipient and poor is the probability of graft survival. This is measured by uptake of  tritium-thymidine into cellular DNA.It is advantageous because it gives an indication of t-helper cell activation in response to class 2 MHC antigen of the graft.
it is disadvantageous for the fact that, it takes several days to run the assay and in case, the donor is a cadavar, the organ should be used asap after it's removal from the cadavar and to wait for the results of the MLR assay becomes a problem.



Minor histocompatibility complex:

The major MHC molecules are recognized directly by helper and cytotoxic T cells by a phenomenon termed as alloreactivity.
In contrast, MHC(minor) antigens are recognized only when they are presented in the context of self-