Topic of research paper is to Differentiate among the types of rejections following transplantation
Transplant rejection occurs when the transplant recipient immune system rejects and attack the newly transplanted tissues or organs. The body’s immune system primarily protects us from harmful substances entering our bodies such as germs, poisons, bacteria, cancer cells and more. These dangerous pathogens have protein covering their surface called antigens. As soon as the antigens enter the body, the immune system flags them off as foreign and proceed to attack them. After an organ transfer, the recipient’s body might identify the new organ or tissues as foreign. The immune system detects the new antigens to be different or unmatched to the rest of the body. Mismatched organs or organs not closely matching the recipient’s body have been known to cause blood transfusion reaction or transplant rejection (Subramaniam & Sakai, 2016).
To prevent this reaction from happening, doctors usually match both the organ donor and recipient. The match is typically not perfect as no two people have identical tissue antigens except identical twins who have identical tissue antigens. Medicines are often used to suppress the immune system in the recipient’s body. The objective is to prevent the immune system from annihilating the transplanted tissue when it is not carefully matched. Failure to use medicines will allow the body to launch an offensive against the newly transplanted organ or tissue destroying it. There are exceptions (Wilkes & Burlingham, 2004). Cornea transplants are seldom rejected as the cornea lack blood supply. A transplant from one identical twin to the other are also almost never rejected. There are three types of organ/tissue rejection, hyperacute rejection, acute rejection, and chronic rejection.
In hyperacute rejection, transplanted organs or tissue is rejected within minutes to hours. Sometimes it happens immediately and is often apparent with the patient still in surgery. This condition is caused by mismatching ABO Blood type of the donor and recipient which has become rare with the advent of modern medical practices. The organ recipient almost always has antibodies against a mismatched donated tissue. The antigen-antibody attacks on the new tissue cause massive thrombosis in the capillaries thus preventing vascularization of the new tissue. For instance, a recipient with Type A blood would contain natural antibodies targeting carbohydrates on the blood of a Type B donor. The existence of preformed antibodies is why rejection occurs almost immediately (Subramaniam & Sakai, 2016). The kidney is most vulnerable to hyperacute rejection while the liver is moderately resistant, probably because it has a dual blood supply. This case may also be because the liver possesses some misunderstood immunologic properties.
Acute transplant rejection is the most prevalent type of rejection and is usually experienced between weeks and months after the transplant procedure. This kind of rejection is carried out by both cell-mediated and antibody-mediated immunity. However, the cell-mediated response takes center stage. All organ recipients experience some form of acute transplant rejection. If identified early enough, acute rejection can be treated though not eliminated with immunosuppressants and corticosteroids. Acute cellular rejection is facilitated by lymphocytes activated against donor antigens especially in the lymphoid tissues of the organ recipient. Once donor dendritic cells enter the blood circulation, they act as antigen-pressing cells (APCs). In humoral rejection, the antibodies may be either preformed antibodies or anti-donor antibodies generated after the transplant (Petechuk, 2006).
Chronic rejection manifests itself months to years after episodes of acute rejection has waned. Chronic rejection is both antibody and cell mediated. Immunosuppressants drugs and tissues typing may increase they life of allografts in the initial years, but chronic rejection is not prevented in most cases. Chronic rejection manifests itself as fibrosis and scarring in a transplanted organ. The actual symptoms depend on the particular organ in question. For example; in heart transplant, chronic rejection appears as coronary artery atherosclerosis. In the case of a lung transplant, it would manifest itself as bronchiolitis obliterans. For liver transplants, chronic rejection is typified by the vanishing bile duct syndrome. For kidney recipients, chronic rejection is known as chronic allograft nephropathy (Wilkes & Burlingham, 2004). It manifests itself as fibrosis and glomerulopathy. Factors that increase the risk of chronic rejection include; previous instances of acute rejection, limited immunosuppression, delayed graft function, donor-related factors e.g. age, existing medical conditions, etc., reperfusion injury to the organ, recipient related actors I.e. age or medical history or even post-transplant infection like cytomegalovirus.
Organ rejection is a phrase that sends shivers down many people’s spines. However, it is not as bad as it sounds. It does not mean that the recipient needs to lose the organ. It is entirely reasonable for a person to have episodes of acute rejection within a year of transplant. Acute rejection may lead to chronic rejection. This situation is when the organ slowly loses effectiveness in dispensing its duties. The threat of rejection subsides with time but an organ recipient is never out of the woods, that is why it is paramount to keep consulting medical practitioners and undergo frequent tests (Klein, Lewis, & Madsen, 2011).
There is a broad range of organ rejection symptoms, and they vary depending on the kind of organ transplant one has had. Some common signs include; pain at the transplant location, feeling unwell, crankiness in children, flu-like symptoms, weight changes, fever, swelling, changes in the heart rate as well as problems with passing urine (Petechuk, 2006). Should an organ recipient exhibit these signs, they should see their doctor as soon as possible.
Organ rejection cannot be completely averted. However, a degree of immune tolerance can be developed through proper medication. Some theories have been put forward to explain the phenomenon of partial tolerance. These are clonal deletion and the development of donor specific lymphocytes, promoting suppressor lymphocytes or factors that reduce the severity of immune responses against the transplanted organ. Other concepts include the introduction of tenacious donor-drive dendritic cells in the recipient that catalyze an immunologically regulated chimeric state between the transplanted organ and the host body.
Cross matching or tissues typing is often performed before an operation to determine whether the donor and recipient are compatible especially for ABO blood group and human leukocyte antigen (HLA). The ABO blood group test is performed first to ascertain compatibility as incompatibility between the blood groups often leads to almost immediate organ rejection. As for the lymphocytotoxicity analysis, a patient’s serum is tested for consonance with donor lymphocytes (Subramaniam & Sakai, 2016). Should the reactivity levels be high, then the transplant may have to pass as it increases the risk of hyperacute reaction. This test is used primarily in kidney transplantation. Transplant candidates with a prior history of blood transfusions, organ transplants, or pregnancies show a high chance of sensitization and have a lower likelihood for negative crossmatch with an organ donor (Wilkes & Burlingham, 2004). Panel reactive antibody (PRA) compares sera from a patient with lymphocytic antibodies in comparison to random cell group. Minimized probability of sensitization for the duration of a second transplant has been shown to be a strong immunosuppressant when combined with anti-thymocyte globulin, tacrolimus, and mycophenolate mofetil/sodium, especially for non-sensitized kidney/pancreas transplant patients. Mixed lymphocyte reaction (MLR) are also employed to determine the degree of main histocompatibility complex (MHC) class I and class II. However, it is a slow test and is often used for cases involving living related donors. It is rare in modern medical practice.
The primary objective of treatment in cases of organ rejection is to ensure that the transplanted tissue or organ dispenses its functions appropriately and to suppress the host’s negative immune system response. Keeping the immune response suppressed my prevent transplant rejection. Medicines will almost always be deployed to suppress the immune system response. The dosage will depend on the nature of the transplant and may be high during the height of rejection (Klein, Lewis, & Madsen, 2011). A lot of people who have undergone a transplant procedure are required to take this medication for the rest of their lives. Even with medication, organ transplants can still fail from rejection. However, single instances of acute rejection seldom cause total organ failure. Chronic rejection is the most common cause of organ transplant failure. The transplanted organ slowly loses its ability to function, and the symptoms begin to show. This type of rejection cannot be effectively combated with medication. In several cases, the patient may need another transplant.
There are two types of Immunosuppressants. Induction drugs is a powerful anti-rejection medication used at the time of the operation. Maintenance drugs are antirejection medications that are taken for the long term. There are usually for classes of maintenance drugs; Calcineurin Inhibitors, these include Tacrolimus and Cyclosporine. Antiproliferative agents which include Mycophenolate Mofetil, Mycophenolate Sodium, and Azathioprine. mTOR inhibitor consists of Sirolimus and Steroids e.g. Prednisone. Some other medicines, food, and supplements may help regulate the levels of immunosuppressants in the blood. The common ones include erythromycin, anti-TB (tuberculosis) drugs, anti-seizure medicines, and common blood pressure medicines e.g. Cardizem and Verapamil or diltiazem (Petechuk, 2006). Natural remedies include grapefruit juice, St. John’s Wort amongst others.
After an organ transplant, a majority of patients quickly regain the feeling of wellbeing. However, they are likely to face massive health challenges. Apart from taking the immunosuppressant drugs for a lifetime, one may also need to take other medication to aid the ‘anti-rejection” drugs do their job or to minimize their side effects (Klein, Lewis, & Madsen, 2011). After a transplant, it is vital for a patient to attend all their doctor appointments and undergo the necessary lab tests as recommended by doctors. The patient should also faithfully take their prescription drugs. It is also important for organ recipients to understand their medication manage their medical schedule, and comprehend how the medicine works as well as learning what the side effects and interaction are, their symptoms and how to handle them. Once a doctor has identified a rejection he/she will attempt to reverse the situation by adjusting the medication. The doctor may switch to a new drug, add another drug or prescribe larger or smaller dose of the drug. During the first few months after a transplant, the doctors will frequently assess the health of the transplanted organ. It is advised to keep healthy habits to enable the body function as optimally as possible.
Wilkes, D. & Burlingham, W. (2004). Immunobiology of organ transplantation (1st ed., pp. 77,110,122). New York: Kluwer Academic/Plenum Publishers.
Subramaniam, K. & Sakai, T. (2016). Anesthesia and perioperative care for organ Transplantation (1st ed., p. 63). New York, NY: Springer.
Petechuk, D. (2006). Organ transplantation (1st ed., pp. 56,79,91). Westport, Conn.: Greenwood Press.
Klein, A., Lewis, C., & Madsen, J. (2011). Organ transplantation (1st ed., pp. 333,360). Cambridge, UK: Cambridge University Press.