14th lecture (transplant rejection) Flashcards
what is the limitation of transplanting organs?
The donor organ is shedding antigens. These antigens are presented by both the donor and recipient APC’s. The recipient lymphocytes start to co-operate with the donor APC.
what is the process occurs during implantation?
1. What is Humoral antibody-mediated reaction?
-organ implanted (cell antigens being shed into the circulation)
-Antigens take up by recipient APC and present it (MHCII) to the CD4+ lymphocytes Antigen will also detect the antigen.
-CD4+ cells will transform in T-helper 2 cells producing IL-4 and IL-5 which will help B cells make antibodies against the implanted cells.
THIS IS a HUMORAL antibody-mediated reaction.
Donor areas can also present their own antigens via MHC1.
what occurs then the CD4+ cells are transformed to T-helper 1 cells?
Describe
2. Delayed type of hypersensitive reactions.
when an antigen is presented the CD4 cells can become T-helper 1 cells. CD4 cells can also detect the donor cells presenting own antigens via own APC.
The T-helper 1 cells will make INF -gamma, INF-alpha.
This will stimulate macrophages invasion.
THIS IS a DELAYED type of hypersensitive reaction.
NOTE: CD4 cells can also become TH2 cells.
Describe 3. T-cell mediate cytotoxicity?
Antigens of the donor organs are presented via MHC1.
Antigens of the donor APC’s are presented via MHC1.
Both of which is recognized by CD8 cells and react to the MHC1.
what are the direct and indirect parts of the transplant rejection? Transplant rejection has 3 parts: 1. antibody mediated humeral reaction. 2. delayed type humoral 3. T cell mediated cytotoxicity
Direct (acute rejection reactions) faster
- CD8 recognizes the MHC1 molecules being presented by the transplanted organ
Indirect (chronic rejection reactions)
APC present antigens to CD4 to then differentiate into Th1 cells.
what is the prototype for transplantation rejection?
the kidney is the most common form of transplantation and therefore the most studied.
Reactions of the transplant rejection are: 1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection Describe the 1st one.
- Hyperacute rejection: the vascular system of the recepiant is connected to the donor blood, within minutes the organ becomes ischemic as the recepiant has preformed antibodies for the organ and thrombotic occlusion of the vessels. Sensitization could occur do to previous transplantation or previous blood infusion.
This is a humeral rejection.
Normally there would be a cross-reaction test with the donor and recepiant serum.
The antibodies attach to the endovascular structure making thrombosis and occlusion of vessels.
Reactions of the transplant rejection are: 1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection Describe the 2nd one.
ACUTE REJECTION:
the whole arsenal of the immune reaction occurs against the organs. This happens within days or weeks. There are humeral and cellular mediate immune reaction parts.
-Cellular part: generates tubiltis: the glomeruli tubules experience lymphocytic infiltration (mostly CD4 T-cells)
-Humoral part: this makes necrotising vasculitis. The vascular structure experiences a fibrinoid necrosis and occlusion with thrombosis.
Reactions of the transplant rejection are: 1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection Describe the 3rd one.
Chronic rejection:
occurs several years after implantation. This mostly affects the vascular system. There is a proliferation of the smooth muscle and Extracellular matrix accumulation, causing slow narrowing of the muscles.
RESULT: ischemia and necrosis of the kidney.
what can be done to extend the life of the graft? What technologies?
- HLE1 and HLE2 checking (HLE2 will have better survivability of kidney)
- All patients with transplantation will have immunosupression, via; corticosteroids, cytostatic drugs.
- blocking of the core receptors (to have an immune reaction co-factors are needed)
what are the co-factors for humoral and cellular reactions, that are blocked during immunosupression?
B7 and CD28, on APC and CD4 cells respectively.
CD3+ T-cells generate the immune reaction, so if they are blocked via drugs, it would be much better then blocking the entire immune system.
what about other organ transplantations other then the kidney: lung, heart, liver?
in this cause the HLE groups analysis cannot be done, because the preservation of the organs are much lower so the transplant need to occur ASAP. They only check major blood groups.
Another limitation is the size of the organ (adult organ may not fit in a child)
describe the 2 types of bone marrow transplantation:
- Autologus (describe this)
- Allogenic
- Autologus bone marrow transplantation: occurs in malignant neoplastic diseases; leukemia, lymphomas. bone marrow is infiltrated by neoplastic cells.
Leukemia: normal bone marrow cells are depressed by neoplastic cells. Chemotherapy to create remission of the disease (reduce neoplastic cells), but relapse can occur. During remission they preforms and BONE MARROW selection by labeling the bone marrow by CD34 (stem cell marker) and they clean the CD34+ cells out of sample and freeze it. Then the patient will have a sub-lethal chemotherapy killing everything, resulting in empty bone marrow. The frozen CD34 stem cells are used to re-populate the bone marrow. Have to be careful to make sure no neoplastic cells remain since there is no immune system to combat them at this point.
describe the 2 types of bone marrow transplantation:
- Autologus
- Allogenic (describe this)
Allogenic bone marrow transplantation. A foreign bone marrow is used
HLE match has to be good. If not then the following occurs:
GVHD (graft vs host disease); In the bone marrow there are different cells that are immunological competent and these cells attack all the cells in the host, and the host has no immune system to defend against. Attack skin and GI tract = lethal,
describe autimmune disease?
in the healthy human body there are autoantibodies and autoreactive cells normally. We need them for normal immune function and we tolerate them, and if the tolerance is lost then the autoimmune disease occurs.
