Organ Trasplantation

Organ transplantation is a treatment of choice to replace damaged organs through the intervention of a donor. There are several types of donors according to their provenance. The donor of organs between two identical twins is called isograft, when donor and recipient is the same individual is called autograft, donor from the same species but different person is called allograft and donor coming from different species with the recipient is called xenograft (Fernandez, 2012). Apart of the above mentioned categories of donors, there are also three categories of donation by living persons.

These are the directed donation to a loved one or a friend, the non-direct whereby donor gives an organ in the general pool to be transplanted in a recipient which is the first person in the waiting list. Finally, there is a directed donation to a stranger where donors have to decide to give their organs to a specific person that they did not have any previous emotional connection (Robert D. and Truog M. D. , 2005). All clinicians should have a good transplant immunology background so as to be more efficient and able to make better alternation in patients’ therapy if needed.

Clinicians play an important role in explaining to patients the novel risk assessment and the treatment strategies and ongoing clinical trials they will go through (Heeger P. S. and Dinavahi MD. R, 2012). Human immune system is divided into innate and adaptive. Innate immunity is rapid but with no memory and little specificity. Innate immunity surrounds cellular components (eg. dentritic cells- DCs and natural killer cells -NKCs) and molecular components (eg. toll-like receptors- TLRs).

Microbial products or endogenous pro-inflammatory ligands are released during the mechanical and ischemia-reperfusion injury (Ischemia-reperfusion is an injury observed when blood supply returns to tissue after ischemia period or reduced amount of oxygen and nutrients resulting in tissue damage) activating the innate immunity to start the initiation of T cells to react against the graft. In both chronic and acute rejection the innate immune cells will be needed both animal transplantation and clinical transplantation (Murphy S. P et. al.

2011). The main function of innate immunity is to identify the pathogens and activate the adaptive immunity through signals, providing the necessary mechanisms to remove pathogens so that healing the relative tissue will be possible. Adaptive immunity has four main characteristics. Specificity arises from the recognition of lymphocyte membrane receptors, that acquire resistance to one microbe and does not confer resistance to others. Moreover clonal expansion of adaptive immunity occurs due to lymphocyte activation and proliferation.

Furthermore memory is another characteristic of adaptive immunity which is present because of the durability of some antigens that stimulates lymphocytes. The immune system “remembers” any previous exposure to infections and responds more efficiently. Self-regulation is a characteristic that arises due to self control and effective withdrawal of antigen as in any other signal response system; there are many feed –back loops of regulation (Fernandez, 2011). Human leukocyte antigens (HLA) are the antigens found on white blood cells, both on recipient and in donors’ blood type.

HLA is classified according to the corresponding Major Histocompatibility Complex (MHC). There are two main types of HLA. HLA class I which is related to MHC I and is presented in antigens to cytotoxic T cells and the HLA class II which is associated to MHC II and is used to antigen- presenting cells for helper T cells. MHC is the main barrier of all allorecognition in vertebrates has the ability to identify tissues of another individual. In invertebrates there is MHC equivalent locus control fusibility. This is the main factor of success or failure of a graft.

It is imperative to donor and recipient to have the best HLA compatibility between them, to avoid rejection because HLA helps in the identification and fight against any “foreign stuff Fernandez, 2012). Recipients should be aware that there is the risk of organ rejection. The rejection of many allografts is mainly caused by the anti-graft effector T cells. Regulatory T cells are created either from specific treatment regimen, or naturally and have an important role in the establishment of long term graft tolerance as well.

By the time host T cells identify graft alloantigens the transplantation rejection starts. Moreover, there are two basic ways to initiate the rejection of transplantation and this is through direct and indirect identification of Major Histocompatibility Complex (MHC) peptides presented by host antigen presenting cells (APC). Tolerance of the graft also depends on T cells. The determination of transplant tolerance is achieved through some mechanisms.

The mechanisms needed to determine the tolerance of the graft are the regulation of T cell activation and differentiation due to cytokine production, minimization of antigen presenting cells (APC) from donor and the inhibition or the knock-out of the effector T cells (Murphy S. P et. al. 2011). Before transplantation both recipient and donor have to go through some tests in order to avoid complications or even the rejection of the organ. Patients have to proceed to screening assays several times against a panel of human leukocyte antigens (HLA).

This is done in order to determine the specificity of the antibodies the complement dependent cytotoxicity (CDC) assay needs to be performed. This assay is done to evade the positive crossmatch and the instant graft loss. For sensitized patients and highly sensitized patients the antibody screening which is done before the transplantation is called “vitual crossmatch”. The positive crossmatch is the transplantation of organs which is incompatible with sensitized patients who are not the proper ones and this has been boosted by United Network for Organ Sharing (UNOS).

On the other hand, in negative crossmatch the transplantation of highly sensitized recipients who are not propitious to receive organ may take place and that is the basis of the Acceptable Mismatch program of Eurotransplant (Roelel D. L et al. 2012). Tissue development techniques and crossmatch testing protect organs avert rejection (Murphy S. P et. al. 2011). There are some complications in performing Complement dependent cytotoxicity assay because target is lymphocyte; the targets of that assay may also be molecules with unrelated cell membrane not just HLA molecules.

The assay based on complement activation and therefore HLA specific IgG antibodies are not able to repair complements like IgG2 and IgG4. Consequently more sensitive assays like antiglobulin and indirect immunofuorescence are used (Roelel D. L et al. 2012). There is an enormous gap between the patients that need organs to survive and the organ availability. In order to increase the rate of patient survival the organ availability has to be increased. Some recent procedures that were developed are using of artificial organs, the amelioration of medicine and the Xenotransplantation.

Artificial organs are very expensive and just few people can afford to buy them. Moreover in such cases the quality of their life is negatively affected and their life span is shorter compared to transplantation (Tisato V. and Cozzi E. , 2012). During the last decades there is an extraordinary development of Xenotransplantation. However, there are some barriers that need to be taken into consideration before a Xenotransplantation. Graft rejection can occur in a couple of minutes during revascularization of the graft due to the hyperacute rejection.

Moreover graft loss is another possibility and can be observed in few days or weeks after transplantation. This can happen due to the acute humoral xenograft rejection. Molecular incompatibility between two different species especially the coagulation flow is another factor to be considered. Animals and humans have impaired anticoagulant and the expression of pro-coagulant molecules on xenograft endothelium. The safety issue is another important factor that needs special attention because clinicians have to assure the recipients for their safety.

Recent improvement has been done to sensitive assays to recognize new infections may occur in xenograft recipients. The diminishment of most known pathogen from animals can be successfully eliminated through the “specific pathogen-free” actions which are the housing and breeding and in particular facilities animals will give birth by caesarean derivation of the possible donor using the correct monitoring environment, although those actions do not eliminate pathogens they just reduce the chances of infection.

Antibodies of the xenograft and complement activation lead to immune mediated injury, and also to graft rejection. In order to avoid graft rejection, resistance to immune mediated injury needs to be accomplished. Up to now the heart Xenotransplantation offers the most long-lasting survival to humans compared with other organs ( Tisato V. and Cozzi E. , 2012).