our p b p n blog.
this is : liveric.blogspot.com
A blog set up for the subject
Principles of Biochemistry & Physiology for Nutrition (PBPN)
by students of A7A1
just for Mdm Kalpana!:D
Our Question:
Our immune system tends to mount an immune response to the entry of an antigen from the same species (e.g. renal transplant).
- Discuss on the factors to be considered to prevent renal transplant rejection.
- Artificial implants (like pace makers, knee/hip joints?) and corneal transplants are not rejected by our immune system? Why?
Topic of Discussion:
* What is Immune System and How Does It Work?
* Renal Transplant Rejection
* Artificial implants and Corneal Transplants
* Q&A Session
* Interesting Facts!!
* Glossary
navigations are on top.=)
Monday, February 9, 2009
Topic:
What is Immune System and How Does It Work?
How Does It Work?
The body's immune system is responsible for defence against foreign substances or called antigen such as bacteria, viruses, parasites and fungi which cause diseases. Once these antigens enter the body, immune system will be triggered to release antibodies which in turn destroy them. Our immune system does not try to attack our own body cells because it is able to differentiate between our body's own cells (self) and foreign cells (non-self). Hence, tissues or cells from other person can be recognised as non-self and this explains why tissue rejection occurs in organ transplant such as renal transplant.
Autoimmune disease
In abnormal condition, the immune system can identify self as non-self and launch an attack against our own body cells. This is called autoimmune disease.
B Cells & T Cells
Lymphocytes or white blood cells are the key role in the immune system' defence mechanism and they are produce by lymphoid organs which can be found throughout the body. Besides travelling via blood vessels, lymphocytes can also travel through the lymphatic vessels which carry lymph that surrounds the body's tissues.
B cells and T cells are the main type of lymphocytes. The role of B cells is to produce antibodies and to fight bacterial infections. When B cells encounter an antigen, they give rise to many large plasma cells which produces antibodies. Each B cell is specific to produce only one type of antibody. The antibody which attacks viruses for influenza is different from antibody that attacks bacterium for pneumonia and these antibodies come from different B cells.
On the other hand, T-cells play a role in fighting viruses and organ rejection in transplant patients.They have receptors on their surfaces which recognise non-self marker. There are 2 major types of T cells namely Helper T Cells (Th Cells) and Killer T Cells also known as Cytotoxic T lymphocytes or CTLs.
Helper T cells act by coordinating immune response by communicating with other cells such as stimulating B cells to produce antibodies and activating T cells while killer T cells directly attack non-self target.
Major Histocompatibility Complex (MHC) Molecules
MHC molecules are proteins recognised by T cells when distinguishing between self and non-self (National Cancel Cell Institute, 2003). T cells only recognise and act on antigen if it is carried on the surface of self MHC molecules. In other words, self MHC molecules bring antigen to T cells so that the T cells will attack it.
MHC molecules are present in almost every cell surface in our body and the MHC molecules of one person differs from another person's. Due to this difference in MHC molecules, organ transplantation becomes difficult as doctor has to find the closest compatibility of MHC molecules between the recipient's organ and the donor. Otherwise, the recipient's T cells will launch an attack against the transplanted organ which lead to rejection.
Natural Killer (NK) cells
They are lymphocytes that recognise and act on antigen in cells that lack self MHC molecules. Hence, they are capable in the destruction of many types of antigen or foreign cells.
Reference:
National Cancer Institute and NIAID(2003) Understanding the Immune System:How It Work
Extracted From:
http://www.niaid.nih.gov/Publications/immune/the_immune_system.pdf
Topic:
Renal Transplantation Rejection
What is renal transplantation?
How does our body reject the newly transplanted kidneys?
And what are the factors to prevent the rejection of the transplanted kidneys?
Renal transplantation is a surgical procedure to replace malfunctioned kidneys that have already reached the end stage of organ failure (Brostoff, Male, Roitt & Roth, 1985).
Our immune system rejects the newly transplanted kidneys as it recognizes the organ to be “foreign” hence attacking the organ leading to rejection. The T cells or T lymphocytes in our body is responsible in rejecting the transplanted kidneys. The T lymphocytes distinguish a “self” from a “non-self” by the protein surface of the Major Histocompatibility Complex (MHC) or Human Leukocytes Antigens (HLA). The HLA cell surface protein of each individual recognizes the own body cells and prevent rejection reactions. The HLA identifies foreign molecules as well, presenting them to the T lymphocytes, which attacks the foreign molecules (University of Pennsylvania School of Medicine, 2008).
There are 3 types of rejection: hyperacute,acute and chronic rejection.
Factors we can prevent the rejection of transplanted kidneys are:
- to match the HLA of donor and recipient as to minimize the chances of rejection OR
- to use immunosuppressive drugs (Brostoff et. al,1985)
The HLA molecules are derived from our parents so it differs in each individual thus matching HLA molecules in transplant is difficult unless donor and recipient are related,example: sibling. There are three classes of HLA loci, HLA-A, HLA-B and HLA-C that need to be matched for the transplantation(Brostoff et. al,1985).
Immunosuppressive drugs are used to control rejection in transplanted kidneys and it work in 3 ways:
Firstly, it inhibits the activation of T lymphocytes. Drugs used are ciclosporin, sirolimus and tacrolimus
Secondly, it inhibits the cell division of T lymphocytes. Drugs used are 6-MP, Azathioprine and MPA.
Lastly, it acts as an anti-inflammatory agent. Drugs used is corticosteroids (Brostoff et. al,1985)
Long term intake of these drugs can lead to high chances of infection.
Reference:
- Brostoff, J., Male, D., Roitt, I., & Roth, D.B. (1985). Immunology: Transplantation and Rejection. Canada: Elsevier Ltd.
- University of Pennsylvania School of Medicine (2008, December 9). Understanding Donor-recipient Genetics Could Decrease Early Kidney Transplant Complications. ScienceDaily. Retrieved February 1, 2009, from http://www.sciencedaily.com /releases/2008/11/081125161540.htm
Sunday, February 8, 2009
Topic:
Artificial implants and Corneal Transplants
Artificial implants such as pace makers and knee/hip joints are usually made of titanium, and is inert in the body. Since MHC is not present on the surface of the implants, our immune system regard these artificial implants as their own and does not try to attack them.
Corneal transplant are not usually rejected by our body’s immune system as it is a type of special collagen and has no blood vessels. Antigens that causes immune response in our bodies has to be in contact with blood vessels. Since there are no blood vessels, leukocytes are not able to attack the transplanted cornea. This is the reason why most of the cornea transplantations are performed successfully.
References
1. www.zampbioworld.org (2009) Prevention Of Organ Rejection In Stable Kidney Transplant Patients - LCP-Tacro™ Moves Into Clinical Phase 3. Retrieved February 1, 2009, from http://www.zampbioworld.org/bionews/index.php/2009/01/02/13684
2. AbsoluteAstronomy.com (2009) Artificial Pacemaker. Retrieved February 1, 2009, from http://www.absoluteastronomy.com/topics/Artificial_pacemaker
3.Advameg Inc. (2007) Corneal Transplantation. Retrieved February 1, 2009, from http://www.surgeryencyclopedia.com/Ce-Fi/Corneal-Transplantation.html
Topic:
Q&A session with Dr. Koji Yo, University of Tokyo
Questions:
1. What are the other causes of renal transplant rejections?
2. What are the most common type of rejections (hyperacute, acute and chronic)?
3. What is immunosuppresin? What are the side effects?
4. Is there any possibility that artificial implants can cause inflammation?
5. How is T-cells responsible for rejection?
1. Besides the rejection by MHC, the antibody in the recipient’s serum can cause hyperacute rejection. Those antibodies are not induced after transplantation, but they are those that the recipient has in his/her body. This rejection is untreatable. In order to prevent this reaction, the existence of the antibodies responsible for the donor’s antigen should be confirmed before transplantion by crossmatch test.
2. Generally, hyperacute rejection is rare, while acute one is quite common. However, because of the progress of drug therapy, acute rejection doesn’t always present the characteristic symptoms, and now it is often difficult to diagnose it precisely.
3. Major immunosuppresins:
Cyclosporine (suppress T cell function)
Side effects: renal toxicity, hypertension, finger tremor etc.
Predonisolone (steroid)
Side effects: diabetes mellitus, gastrointestinal ulcer, cataract etc.
Azathioprine (block DNA synthesis and T cell proliferation)
Side effects: loss of leukocytes, hepatotoxicity etc.
All of them may cause severe infection.
4. Taking pacemaker as an example, there are two kinds of risks of infection. One is the infection at the skin where the pacemaker is planted, and the other is the lead inserted into the heart. To prevent the infection, antibiotics are used after the operation for a few days.
5. Helper T cells or Th cells recognize non-self antigen with MHC presented on the cell surface of the recipient’s own antigen presenting cells. Th cells are activated and produce proteins called cytokine that mediate the inflammation process. Differentiation of T cell into cytotoxic T cell (CTL) occurs. CTL attacks the cells from the donor by penetrating the cell membrane and destroying the DNA of the target cells or by inducing cell death called apoptosis through the cell membrane protein called Fas.
Topic:
Interesting Facts!!
1. Human twins have the same set of MHC molecules on their cell surfaces.
2. The lifespan for B and T cells is days to years.
3. Both B and T cells can develop into lymphoma, a cancer of the white bloos cells with B-cell lymphoma being more a more common occurence than T-cell lymphoma.
4. With the advancement of technology in medical industry, artificial kidneys are now available for dialysis and transplantation! Patients would receive treatment of 12 hours a day, twice or thrice weekly. In 1-2 months, the treatments will remove all symptoms of kidney failure.
5. The first artificial implant ever created was a heart pacemaker in 1959 in Sweden.
6. Since 18th century, researchers have been experimenting with organ transplantation on animals and humans.
7. If one person is to donate an organ and tissue, he can sustain or increase the life conditions of over 50 people.
8. There is a short period of time that the organs can be out of the body.
Heart: 4-6 hours
Lung: 4-6 hours
Liver: 12-24 hours
Kidneys: 48-72 hours
Wednesday, February 4, 2009
Topic:
Glossary
Antibody: A soluble protein molecule produced and secreted by B cells in response to an antigen, which is capable of binding to that specific antigen.
Antigen: Any substance that, when introduced into the body, is recognized by the immune system.
Artificial Implant: Replacement of damaged or malfunctioned organ or tissue to an artificial one.
Donor: A person who gives his/her organ to a recipient.
Histocompatibility Testing: A method of matching the self antigens (HLA) on the tissues of a transplant donor with those of the recipient. The closer the match, the better the chance that the transplant will take.
Human Leukocyte Antigens (HLA): Protein in markers of self used in histocompatibility testing. Some HLA types also correlate with certain autoimmune diseases.
Immune Response: Any defensive reaction to foreign material by the immune system.
Immunosuppression: Reduction of the immune responses, for instance by giving drugs to prevent transplant rejection.
Lymphatic system: The vessels, tissues and organs that store and carrylymphocytes that fight infection and other diseases.
Lymphocyte: a type of white blood cell.
Major Histocompatibility Complex (MHC): group of genes that controls several aspects of the immune response. MHC genes code for self markers on all body cells.
Recipient: A person who receives the donated organ.
Renal Transplant: A surgical procedure to replace malfunctioned kidneys which have already reached end-stage kidney disease.
Reference: