Why Does the Body Reject Transplanted Organs?

Organ transplants are a medical breakthrough that gives people a second chance at life when their organs stop working. The kidney is the organ most often transplanted around the world.

Kidney transplants make up nearly 60% of all transplants globally. This high number is because many lifestyle choices lead to kidney failure, which may require a transplant to save a person’s life. 

The need for kidney transplants is also greater because people can live on dialysis while waiting for a suitable donor.

This makes it easier to find the best match for them. This is different from other organs like the heart or liver, where patients might not have as much time to wait.

However, one big challenge after a transplant is the risk of the body rejecting the new organ. Even with medical advances, organ rejection is still a significant problem.

Understanding Organ Rejection

Around 15% to 20% of people who receive a kidney transplant will face some rejection. Organ rejection is a complex response from the body’s defense system, which naturally sees anything not originally part of the body as a threat.

The immune system, which protects the body from invaders like bacteria and viruses, also reacts to transplanted organs. It’s made up of cells, tissues, and organs that work together to find and destroy these invaders.

When a new organ is transplanted, the immune system treats it as an outsider and attacks it, just like it would attack a harmful virus.

The Mechanisms of Rejection

HLA Mismatch: The Root Cause

Human leukocyte antigens (HLAs) are molecules on cells that help the immune system tell the difference between the body’s own cells and outsiders. Everyone has a unique set of HLAs, inherited from their parents. When a donor organ has different HLAs, the immune system sees these as a threat and attacks the organ.

T-Cell Activation: The Immune Response

T-cells, a type of white blood cell, play a key role in rejecting organs. They get activated when they recognise foreign HLAs and then attack the transplant by releasing harmful substances and directly killing cells in the new organ. This can lead to acute rejection, which usually happens within weeks or months after the transplant.

Antibody-Mediated Rejection

Besides T-cells, the body can make antibodies that target the transplanted organ. These antibodies attack specific markers on the donor organ’s cells, leading to antibody-mediated rejection (AMR), which can cause severe damage to the organ.

Types of Organ Rejection

Hyperacute Rejection

This happens within minutes or hours after the transplant. It’s caused by pre-existing antibodies in the recipient’s blood that immediately attack the donor organ. This type of rejection is rare but very serious, often resulting in the loss of the transplanted organ.

Acute Rejection

This is more common and occurs within the first few months after the transplant. It involves a response from the T-cells and can usually be managed with drugs that suppress the immune system if it’s caught early.

Chronic Rejection

This type happens over years and leads to a slow loss of the organ’s function. It’s caused by ongoing, mild immune responses that eventually cause scarring and damage to the organ.

Managing Rejection

To prevent rejection, people who receive transplants must take drugs that suppress their immune system for life. These drugs reduce the chance of the immune system attacking the transplanted organ.

However, getting the balance right is hard; too little suppression can lead to rejection, while too much can increase the risk of infections and other health issues.

Organ rejection shows both the strength and the challenges of the immune system. The system meant to protect us can sometimes harm us, especially when a foreign organ is involved.

Understanding rejection has led to better matching methods and more effective treatments, but it remains one of the toughest parts of organ transplantation.