Transplant Immunology

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Most people know that rejection of transplanted organs is a serious issue that has to be accounted for before a recipient even gets a donor organ. But why is it a problem? Fewer people know that this phenomenon actually has an immunological basis.

The immune system has evolved to recognize two basic categories of molecules: self and non-self (the molecules the immune system recognizes are called antigens). When it recognizes self antigen, the immune system fails to activate. However, the recognition of non-self antigen triggers a complex chain of reactions that results in an immune response targeted towards elimination the source of those antigens – typically a bacterial or viral pathogen.

So if the immune system recognizes non-self, how is it that a transplanted organ can trigger an immune response in the recipient? After all, the donor organ is of human origin.

The problem is, humans are not all genetically identical, and the genetic difference is enough to trigger an immune response to donated organs and tissues.

The Basis of Transplant Rejection

Rejection of transplanted organs typically occurs as a result of an immune reaction to antigens called human leukocyte antigens. And interestingly enough, these molecules are actually an integral part of the human immune system.

Human leukocyte antigens (also known as the majorhistocompatibility complex, or MHC) are involved in a process called antigen presentation. This process, which occurs more or less constantly in most cell types, involves the processing of antigens which the cell manufactures or ingests from the extracellular environment.

The antigens are packaged up with the MHC, and the entire unit is then transported to the surface of the cell. On the surface, that unit interacts with immune cells (this process is called antigen presentation). If the antigen is non-self, an immune response is activated against the antigen.

So what does this have to do with transplant rejection? MHC molecules from the donor tissue can get presented by recipient cells. And because the donor MHC is different from the recipient MHC, the donor MHC can trigger an immune response.

When this happens, a response is activated against the donor organ. The reaction may be acute, occurring within 24 hours and mediated by antibodies against the donor blood type (antigen presentation is not required for this), or delayed, occurring within around a week. The delayed reaction occurs when T cells become activated against the donor tissue (following antigen presentation).

Preventing Transplant Rejection

There are two ways to prevent or reduce the likelihood of transplant rejection. In most situations, both methods are used.

The first occurs before an organ is transplanted to a recipient, and is called tissue matching. This involves matching the MHC type of the recipient and the donor as closely as possible, to reduce the possibility of an immune response occurring against the donor tissue. And this, in turn, is why close relatives typically make the best donors – they are more likely to have MHC types that closely match those of the recipient (also meaning that identical twins are the best possible donor).

The requirement for a tissue match is one reason why transplant recipients must often wait a long time for a donor organ – they simply have to wait until an organ that is a good match becomes available. Transplanting an organ into a recipient that is a very poor match would be a waste of an organ (and might endanger the life of the recipient), as a rejection episode would be a very likely outcome.

The second way to prevent rejection is through the use of drugs which dampen the immune system. However, while the objective is to prevent transplant rejection, in the long term the drugs may cause their own issues – not the least of which is that the recipient’s immune system is suppressed overall, leaving them susceptible to infection.