- Shuffle
Toggle OnToggle Off
- Alphabetize
Toggle OnToggle Off
- Front First
Toggle OnToggle Off
- Both Sides
Toggle OnToggle Off
Front
How to study your flashcards.
Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key
Up/Down arrow keys: Flip the card between the front and back.down keyup key
H key: Show hint (3rd side).h key
PLAY BUTTON
PLAY BUTTON
38 Cards in this Set
- Front
- Back
|
What are the three main approaches to decrease graft rejection during transplantation?
|
Screen for pre-formed antibody (IgM usually)
Decrease immunogenicity of graft Block immune response to graft |
|
When screening for pre-formed antibody, what adverse effect is trying to be prevented?
|
Hyperacute rejection
|
|
What are the most common antigens that can cause hyperacute rejection?
|
ABO blood antigens in blood and on blood vessel endothelium
|
|
How is the immunogenicity of the graft decreased in the case of a transplant?
|
HLA matching
- Try and best match MHC genes |
|
Why is HLA matching usually only done in renal allografts?
|
Takes time
Cannot wait this long for other organ transplants; kidney OK |
|
What are the different methods used to block immune responses to graft tissue?
|
Small molecule immunosuppressants
Steroids Cyclosporin A & FK506 Rapamycin Antibody and fusion proteins |
|
What are examples of small molecule immunosuppressants and how do they work?
|
6 Mercaptopurine
Azithioprine imuran Mycophenolate mofetil These inhibit DNA synthesis and cell proliferation by inhibiting purine synthesis |
|
What are some cons to using small molecule immunosuppressants to block an immune response to graft tissue?
|
These inhibitors affect other rapidly dividing tissues (bone marrow, GI)
|
|
How do steroids block the immune response to graft tissue?
|
Inhibit cytokine production
Inhibit granulocyte function and inflammation Kill lymphocytes |
|
What are some cons of using steroids to block immune responses against graft tissue?
|
Hypertension
Doabetes Hyperlipidemia Osteoporosis |
|
By what mechanism do cyclosporin A and FK506 block immune responses to graft tissue?
|
Inhibit calcineurin; a phosphatase required for IL-2 and IL-2R production leading to T cell proliferation and differentiation into effector cells
|
|
What are cons of using cyclosporin A and FK506 to block immune responses to graft tissue?
|
Nephrotoxic
Hypertension Diabetes Dyslipidemia Hirsutism (cyclosporin A) Gingival hypertrophy (cyclosporin A) |
|
By what mechanism does rapamycin block immune responses to graft tissue?
|
Inhibits mTOR; a kinase required for cellular proliferation
|
|
What are cons of using rapamycin to block immune responses against graft tissue?
|
Hyperlipidemia
Thrombocytopenia |
|
How is it possible to tell whether a kidney transplant is deteriorating due to drug toxicity from cyclosporin A or whether the immune system is rejecting the graft?
|
Fine needle biopsy of kidney tissue
|
|
What types of antibodies and fusion proteins have been used as immunosuppressants?
|
Anti-lymphocyte globulin
OKT3 Daclizumab ad Basliximab |
|
How do anti-lymphocyte globulin antibodies suppress the immune system and what are some cons of using this treatment?
|
Bind T cells and inactivate them
Cons: - Serum sickness - Cross reactivity with granulocytes and platelets, leading to granulocytopenia and thrombocytopenia |
|
How does the antibody, OKT3 suppress the immune system and what are some cons of using this treatment?
|
Binds to the CD3 component of the TCR, leading to apoptosis of the T cell
Cons: - Some initial T cell activation leads to cytokine release syndrome |
|
How do daclizumab and basliximab suppress the immune system and what are some cons of using this treatment?
|
Anti IL-2 and IL-2R antibodies, killing the T cells
Cons: - None |
|
What are the major problems of immunosuppression when preventing graft rejection?
|
Drug toxicity
Not 100% effective Increased risk of malignancy INFECTION |
|
What is the ideal therapy for eliminating the chance of graft rejection?
|
Induce tolerance of T cells to graft antigens
|
|
What is one way by which tolerance could be induced in T cells to avoid graft rejection and what is an example of this attempt?
|
Block the costimulatory signal required to activate T cells
- CTLA4Ig blocks B7 from binding to the CD28 receptor (costimulation) |
|
What are problems with blocking costimulation to induce tolerance to graft antigens?
|
Perhaps good for naive T cells
Not so good against memory cells |
|
For how long are patients with transplanted tissues treated with immunosuppressants?
|
Forever
|
|
How does immunosuppressive therapy altered during periods of acute rejection?
|
Intensified
|
|
What are potential solutions for the problem of organ shortage for transplantation?
|
Pay kin for organs?
Bionics: artificial organs Tissue engineering via stem cells Xenotransplantation |
|
What animals would be ideal for xenotransplantation?
|
Primates (though scarce and ethically confusing)
Food animals: - Pigs - Cows |
|
What are cons of xenotransplantation?
|
Hyperacute rejection
Cellular and humoral rejection Animal viruses and other pathogens |
|
What causes hyperacute rejection in the instance of a xenotransplantation and how can this be fixed??
|
Natural human antibodies cross react with carbohydrates on graft endothelium
Solutions: - Knockout glycosyltransferase in donor animal - Create transgenic pigs resistant to complement attack |
|
In what clinical settings are allogenic bone marrow transplants used?
|
Bone marrow defects
Cancers of hematopoietic system High dose chemotherapy (to rescue bone marrow) |
|
How is bone marrow transplanted in a patient?
|
Transfused intravenously
Stem cells home to bone marrow (need space in bone marrow) |
|
What is the reason for the rejection of allogenic bone marrow stem cells?
|
NK cells reject stem cells as they don't recognize allogenic MHCs
|
|
What are complications associated with bone marrow trasnplantation?
|
Graft vs. host disease
Failure to engraft Immunodeficiency Infection |
|
What causes graft vs. host disease?
|
Mature T cells and NK cells from donor bone marrow attack the host
|
|
What sites are particularly affected in graft vs. host disease and how does this present clincially?
|
Skin epithelium: rash
Biliary epithelium: jaundice GI epithelium: diarrhea |
|
How is graft vs. host disease prevented?
|
HLA matching
Eliminate mature T cells in bone marrow |
|
What are cons of eliminating mature T cells in donor bone marrow before transplanting to avoid graft vs. host disease?
|
T cells:
- Help engraftment - Attack tumors |
|
How is graft vs. host disease treated?
|
Intensive immunosuppression
|
