Transplant Immunology

Organ transplantation, a fascinating and complex field of medicine, is relatively new. To comprehend it, we must delve into the intricacies of all the pre-transplant and post-transplant procedures. 

Let us start by reading about the types of grafts:

1. Autograft - Graft taken from the same individual
2. Isograft - Graft is taken from Identical twins
3. Allograft - Grafting done between the same species. For example, Kidney transplant or bone marrow transplant from Human to human
4. Xenograft - Grafting is done between different species. For Example: Prosthetic heart valves that are taken from different animals. Porcine and bovine are the different types of heart valves that are being used there days.

In the context of organ transplantation, the individual who receives the graft is referred to as the recipient, while the one who donates the graft is known as the donor. Once a suitable graft is identified, the crucial steps of blood matching and HLA matching come into play. 

Rest assured, the crucial steps of blood matching and HLA matching are meticulously followed in organ transplantation. Certain percentages are pre-decided for HLA matching. For bone Marrow, 100% matching is needed. For kidney transplants, 50% matching is required. The cornea does not require HLA matching because it is an avascular structure. For Heart/ liver /Lung transplants, HLA matching—viability test is the first priority because Vitality will be gone if waited.

Therefore, immunosuppressive drugs should also be started with all transplants except corneal transplants.

For HLA matching, the Ideal match in adult Genes that are targeted are HLA, A, B, C, DQ, and DR. The criteria followed is a Minimum of 8 on 10 should be matched. But what is practically matched are HLA, A, B, C & DR, and the Criteria of a minimum of 6 out 8 should be matched. For children, HLA A, B, and DR genes are to be considered, and the Criteria: a minimum of 4 out of 6 is matched. For Identical Twins we get a perfect 6/6 alleles matched.

The most important matching is DR matching.

Post transplantation, there are two main issues that occur they are transplant rejection and graft versus host rejection. We will first read about the Types of Transplant Rejection. It is mainly of three types:

1. Hyperacute Rejection: it occurs within the first 48 hours. It is a Type 2 Hypersensitivity reaction. Most of the time, it happens on the operation table itself. The reason for this rejection is PREFORMED ANTIBODIES. For example, A kidney (donor graft) is placed and is provided the blood supply. But the recipient rejected it. There will be certain patients who will have pre-formed antibodies. They will have a history of previous multiple blood transfusions and Multiparous women.
2. Acute rejection: it occurs between a few days to weeks and is rejected after that. It is a Type 2+4 Hypersensitivity reaction.
3. Chronic Rejection: this is the most common type of rejection. It is a Type 4 Hypersensitivity reaction. Self-antigen-presenting cells are going to activate CD4 T cells. Then, CD4 cells differentiate into: T helper 1 cells, IFN gamma, and granuloma of Epithelioid cells. There will be some peculiar features present in the Kidney, like GBM duplication - in which the Glomerular basement membrane duplicates, Obliteration/sclerosis of blood vessels, Tubular atrophy - Atrophied, and Interstitial fibrosis.

Microscopically, some important changes are also seen in transplantation. They are Fibrinoid necrosis in the blood vessels, the presence of Intraluminal thrombi, and coagulative necrosis in the solid organs. Necrosis always shows inflammation and neutrophilic infiltration.

The doctor/ surgeon can know about the rejection by looking at the Kidney and urine urine.

The kidney becomes floppy and turns blue due to no supply of blood, and there is the presence of blood in urine.

We will now read about Graft Versus Host Disease. In this disease, the Donor graft attacks the recipient. For example, The transplanted kidney attacks the receiver because the Donor is immunocompetent, whereas the Recipient is immunocompromised. It can be classified into two types:

1. Acute GVHD occurs within 100 days of the transplant. Changes are visible on the Skin as Rash, in the GIT as Diarrhea, and in the Liver as Jaundice.
2. Chronic GVHD occurs after 100 days of transplant. It is seen on the Skin as Fibrosis, in the Intestine, it causes stricture; and in the Liver - Fibrosis. 

The last topic that needs to be included in this blog is the various Post-Transplant Complications that can occur in a patient. As the patient is immunocompromised, they might get infected by Cytomegalo Virus infection and BK virus. BK virus belongs to the POLYOMAVIRUS DNA family. The GVHD patient’s Urine microscopy examination shows decoy cells.

As we discussed, this Immunosuppressive state of the patient can make him more prone to infections like Human papillomavirus - cervical cancer, EBV, and HHV8.

Transplant immunology is very interestingly discussed by our renowned Dr. Preeti in both the subjects of pathology and microbiology by the name of “transplant immunology”.

Also Read: Myxoviruses: Structure, Function, and Impact on Health

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