The first problem all heart transplant recipients face if they survive surgery is donor organ rejection. Your body ejects any foreign substance that penetrates it - to get rid of invaders. This is a good thing. Unfortunately, your body considers your donor heart an invader and is going to try to eject it from your body.
New theories of how to prevent rejection are emerging. Heavily suppressing the immune system like we do now may actually prevent your body from accepting a new organ. It may be possible to persuade your body to accept a donor organ (tolerance) without heavily suppressing your immune system. This would leave your body able to fight infection normally and would reduce the drastic side effects from anti-rejection drugs. Read more at Transplant Update. For now you will receive therapy for rejection as explained below.
New treatments for acute rejection are also emerging. One is photopheresis. See this page and this page for more about this light-based therapy. It's interesting reading. :-)
Risk of heart rejection is highest right after transplant surgery. In one study, the first year after transplant 37% of patients had no rejection episodes, 40% had one episode, and 23% had more than one episode. This is why induction therapy is used. Induction therapy is the use of OKT-3 or other heavy-duty drugs to really max out your anti-rejection treatment right after your transplant surgery.
You will keep taking some anti-rejection drugs for the rest of your life. Further down the page, I explain the actual physical rejection process in 3 versions - short, medium, long. First, I give the info you're most likely to want - how rejection is rated and treated.
There are different kinds of organ rejection but everything on this page is geared toward "acute cellular" rejection. Eighty-five percent of rejection espisodes are of this type. Here is a brief outline of other rejection types:
Acute Organ Rejection - ISHLT Grades and Treatment | |||
Grade | Patients Status | Early (less than 3 months) | Late (after 3 months) |
0 | Stable | No changes | Standard immunosuppression |
1A | Stable | No changes | Standard immunosuppression |
1B | Stable | No changes | Adjust drug doses |
2 | Stable | No changes | Adjust drug doses |
2 | Unstable, meaning: rising CVP and PCWP, decreasing EF arrhythmias and other symptoms |
Increase drug doses possibly add 100mg prednisone TID |
Same as for early treatment |
3A | Stable | Increase drug doses 100mg prednisone TID |
Same as for early treatment |
3A | Unstable, meaning: rising CVP and PCWP, decreasing EF arrhythmias and other symptoms |
one gram IV prednisone Increase drug doses |
Same as for early treatment |
3B | Stable | one gram IV prednisone Increase drug doses |
100mg oral prednisone TID |
3B | Unstable, meaning: rising CVP and PCWP, decreasing EF arrhythmias and other symptoms |
ALG, ATG, or OKT3 for 7 to 10 days | one gram IV prednisone for 3 days |
4 | Irrelevant | ALG, ATG, or OKT3 for 7 to 10 days |
Patients with mild rejection usually take oral prednisone. If they are also having heart function problems, they may get "pulse methylprednisolone" - IV steroids - once a day for for 3 to 5 days. This works about 50 to 60% of the time. If that does not do it, you are said to have "steroid resistant rejection."
In that case, you'll probably get monoclonal or polyclonal antibodies - OKT3, ALG, ATG. You can think of these as anti-T-cell antibodies, which bind to, and destroy, your T-cells. There are 2 more recently approved monoclonal antibody treatments: daclizumab (Zenapax) and basiliximab (Simulect).
The immune system recognizes as foreign and attacks anything different from your normal body tissues. Even substances that are only a little bit different, like a transplanted human heart, are considered foreign invaders.
When an organ is transplanted, a small part of the donor organ is recognized as foreign and your immune system attacks it. To lower the chances of transplant rejection, donors who share as many MHC genes as possible with the transplant recipient are preferred. Even then, most transplant recipients are given lots of drugs to suppress their immune response and prevent organ rejection.
If the transplanted tissue contains T-cells from the donor, these donor T-cells may recognize the recipient's tissue as foreign and attack them. This can be fatal and is called graft-versus-host (GVH) disease. This is prevented as much as possible by trying to remove all donor T-cells from the donor organ before transplant takes place.
By 1863, Paul Bert had shown that tissues transplanted from one person to another are rejected. Forty years later, Carl Jensen proved that this rejection was carried out by the immune system.
To do its job, your immune system must know what is an invader and what isn't. This recognition system uses markers called histocompatibility antigens. These antigens are found on the surface of every cell in your body. The immune system attacks anything without the proper identifyers. "Unrecognized" antigens include those on invading viruses and bacteria. Your immune system has no way to tell if tissue is harmful or not, just if it is different. Your "new" heart is different as far as your immune system is concerned, so it's got to go!
In 1958, Jean Dausset discovered the histocompatibility system for "matching" tissue types. The ability to reduce histocompatibility differences is one of the things that makes heart transplants possible. The usual name for this "matching" is HLA or "Human Leukocyte Antigen" matching.
There are over 200 different histocompatibility antigens. Each person has a certain "set." The odds that 2 unrelated people will have the same set are about one in 30,000. Transplant coordinators try to match histocompatibility antigens of the donor and the recipient as well as possible to minimize rejection. You are part of a "match" program through UNOS, but due to the very short life of a heart outside a body, exact cross-matching for heart transplant is done after surgery has begun and only helps decide how strong your anti-rejection therapy will be. The match is never exact, so you must take drugs to suppress your immune system's response.
The first drugs used for this were azathioprine and prednisone. Those drugs suppress the entire immune system, leaving you wide open to infections and cancer. They also have some very nasty side effects.
The next breakthrough was cyclosporine, which comes from fungus found in dirt from a certain area. Cyclosporine suppresses the part of the immune system involved in organ rejection without suppressing the entire system completely. This allows you to prevent rejection without being quite as vulnerable to infections.
A few years later, another fungus product, tacrolimus (FK-506 or Prograf), was found that is even better for kidney, liver, heart, and lung transplants. However, patients who take these drugs still face increased risk of infection and cancer, and the drugs can cause kidney damage. A combination of immune-suppressing drugs is used to try to prevent severe side effects.
It was not until cyclosporine was approved for use in the United States in 1983 that heart transplants gained widespread use. Now, about 83% of heart recipients survive the first year.
There are 2 kinds of immunity: innate and adaptive. Innate immunity is the body's first line of defense. Innate immunity is provided by barriers like skin, tears, mucus, and saliva, as well as by rapid inflammation of tissues. As a woodworker, I can vouch that this inflammation will actually push foreign objects like splinters out of your skin all on its own.
If an invader gets past this first line of defense, your immune system makes a customized defense. Your immune system can call upon this defense later if the same invader attacks again. This is called adaptive immunity and it has 4 characteristics:
Immune responses are actually reactions to structures on the surface of invading organisms called antigens. There are 2 kinds of immune responses:
Humoral immune response White blood cells are the mainstay of the immune system. Some white blood cells, called macrophages, surround and "eat" invading bacteria. Macrophages can also attach to invading antigens and deliver them to other parts of the immune system to be destroyed.
Lymphocytes are specialized white blood cells which identify and destroy invading antigens. All lymphocytes begin as "stem cells" in your bone marrow, but they mature in 2 different places. Some lymphocytes mature in the bone marrow and are called B-lymphocytes. B-lymphocytes make antibodies which circulate through bodily fluids, sticking to antigens and destroying them.
Other lymphocytes called T-lymphocytes or T-cells mature in the thymus, a small organ behind the breastbone. Some T-cells called cytotoxic or "killer T-cells" directly destroy cells that have certain antigens on their surface.
"Helper T-cells" regulate the immune system by controlling the strength of immune responses. Lymphocytes constantly travel throughout the blood, looking for invaders.
Each immune response is tailored to a specific kind of invading antigen. Each lymphocyte has an antigen receptor - a structure on its surface - that can bind to a matching structure on the antigen, like a lock and key. Although lymphocytes can make billions of different kinds of antigen receptors, each individual lymphocyte makes only one.
When an antigen enters a body cell, transporter molecules inside the cell attach themselves to the antigen and transport it to the cell's surface, where the antigen is caught by a T-cell. These transport molecules are made by a group of genes called the major histocompatibility complex (MHC) and are therefore known as "MHC molecules." The humoral immune response works something like this:
The antibodies from step 6 and 7 are Y-shaped proteins called immunoglobulins (Ig) and are only made by B-cells. The antibody binds to the antigen at the ends of the arms of the Y. The base of the Y decides how the antibody will destroy the antigen. This area classifies antibodies into 5 classes: IgM, IgG, IgA, IgD, and IgE. Which Ig classes a B-cell makes depends on the kind of interleukins it gets from the T-helper cells.
Antibodies may be able to stop the harmful effects of an antigen simply by binding to it (neutralizing it), which may stop it from causing any further harm. All classes of antibodies can neutralize antigens. Antibodies also help destroy antigens by getting them ready to be eaten by macrophages. The antibodies coat the surface of antigens. Antigens coated with antibodies are more likely to stick to a macrophage and be eaten.
Cell-mediated immune response As with humoral immune response, this involves a complex chain of events after antigens enter the body. Helper T-cells are required, which bind the antigen and are thereby activated to divide and produce interleukins. The interleukins activate killer T-cells.
Material taken from various sources, including Microsoft's Encyclopedia Encarta - Updated June 3, 2002
All information on this site is opinion only. All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor. Use the reference information at the end of each article to search MedLine for more complete and accurate information. All original copyrights apply. No information on this page should be used by any person to affect their medical, legal, educational, social, or psychological treatment in any way. I am not a doctor. This web site and all its pages, graphics, and content copyright © 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004 Jon C.