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57 Cards in this Set
- Front
- Back
Define Autograft (ie Autologous)
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Pts own tissue
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Define Isograft (ie Synergeneic)
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Graft from Identical genetic individuals (I=Isograft)
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Define Allograft
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A = Another Person (vs. Auto = pts own tissue)
Graft from another person |
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Define Xenograft
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Graft From Animal of dif. species (X=diff. species)
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Histocompatibility
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Property of having the same or mostly the same alleles ie Major histocompatibility complexes (2 in 10,000 people will be identical at MHC 1 and MHC 2, 1 in 4 siblings will have identical)
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Where are MHC 1 and 2 expressed?
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most tissues
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Define Alloantigen
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Antigen thats part of our self-recognition ie major histocompatibility antigen
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Define minor histocompatibility antigen
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Receptors on cell surface of donated organs that are known to make immunological response...but less of a problem than major histocompatibility
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Define graft rejection
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MHC alleles recognized as foreign by recipient's immune system
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What are the 3 classes of transplant rejection?
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Tissue Solid Organ, Bone Marrow
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Whats the most common transplant
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Blood
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T/F: 45 y/o pt is undergoing a corneal transplant for diabetes-related issues. Do you need to give them immunosuppressive drugs?
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NO, corneal transplants don't need ummunosuppressive drugs
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Whats the difference between solid organ transplant disease and Graft vs host disease?
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solid organ transplant disease = differences in HLA I and HLA II (human leukocyte antigens I and II) = MHC class I and II. Recipient's T cells attack transplant.
Graft vs host diease = Bone Marrow/stem cell transplant = T cells IN TRANSPLANTED MATERIAL ATTACK RECIPIENT tissues |
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Whats the role of B cells role in transplant rejection?
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Some plasma cells become established in bone marrow - they proliferate and become long-term Ab factories
Donor-specific Abs play a role in acute rejection |
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What are the most important things to type for to avoid rejection?
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HLA-A
HLA-B HLA-DR |
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Why is HMC diversity so important?
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So we can survive many diff types of insults (ex. - HIV)
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What are the 3 types of rejection?
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Acute (min-hrs), Hyperacute (days-wks), Chronic (months-yrs)
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What will you most likely NOT see in the medical setting today b/c its readily screened for?
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HYPERACUTE rejection
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What occur to some extent in nearly ALL transplants?
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ACUTE rejection - WHY we use IMMUNOSUPPRESSANTS
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How does Chronic rejection manifest?
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GRADUAL decline in graft function
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T/F: Chronic rejection is unpredictable and heterogenous in nature
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TRUE
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Whats the cause of Hyperacute rejection?
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PRE-FORMED Anti-donor Abs to ABO or MHC and complement --> graft destruction --> can't treat, lose graft
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Which type of rejection can we NOT treat?
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HYPERACUTE. Abs already formed
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How do we prevent a HYPERACUTE rejection?
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cross-match test ie recipient AB vs Donor cells --> see if lysis occurs
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How does Acute rejection occur?
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Donor Dendrites activated by inflamm and migrate to recipient's spleen or lymph nodes --> Here they encounter T cells
Donor dendritic MHC I and II recognized as foreign by CD8 cytotoxic T cells --> activated T cells destroy graft by releasing porphyrin and granzyme |
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What do CD8 cytotoxic T cells release to destroy graft in Acute rejection?
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Granzyme and Porphyrin
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How do CD4 Helper T cells help cause damage in acute rejection?
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Activate macrophages via secreting inflamm cytokines = Type IV hypersensitivity rxn
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How do chronic rejections occur?
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Ab-complement rxn in graft vasculature --> dec. blood to graft --> ischemia
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What enters the tissue of grafts from chronic rejections, leading to damage?
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immune effectors
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Which is expressed on vascular endothelium, HMC I or MHC II?
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MHC I
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How do Abs mediate the damage seen in chronic rejection?
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Recruit inflamm cells
Activate Complement Mediate Ab-dependent cellular toxicity |
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How are T cells activated in Acute vs Chronic rejection?
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Acute = DIRECT Chronic - INDIRECT
In Acute, the graft itself has antigen presenting cells like dendrites that present SELF-peptide to recipient T cells. In Chronic, Allopeptide (from the graft) is presented to CD4 T cells by the recipient's OWN dendritic cells, NOT the dendritic cells of the graft. |
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Allopeptide is presented to a CD4 T cell via MHC II. Is this Acute or chronic rejection
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CHRONIC
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Self peptide from a graft is presented to CD4 T cells via MHC II. Is this acute or chronic rejection?
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ACUTE
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Describe the Cross-match test...
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Donor B cells and Donor T cells in blood are mixed with Recipient Blood, Complement and Dye.
If the Recipient has Abs to Anything present on the donor's T CELLS (not B cells...) the sample will Lyse and this is considered a POSITIVE rxn and the samples are NOT compatible. |
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In which tissue is transplantation most sensitive to HLA display?
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Bone Marrow
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What are some sources of stem cells?
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bone marrow, cord blood, peripheral blood (=normal blood)
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We can see rejection of bone marrow in all pts EXCEPT those who...? (ie what pts will NOT develop GVHD, graft vs host disease?)
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Have Immuno-compromised disease (= they can't mount immune response to bone marrow trancplant)
SCID, Agammaglobulinemia, Hyper IgM Syndrome, Selective IgA deficiency etc. |
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What diseases can be treated with bone marrow transplant?
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Primary immunodeficiencies
Some Leukemias Aplastic Anemia Autoimmune disease |
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How does GVHD occur?
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T cells in Transplanted bone marrow are activated against recipient MHC
Recipient MHC class I recognized by sensitized CTLS = killing of mucosal and epi cells |
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How does GVHD manifest?
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NOTE: Skin, Liver, GI - major sites
Skin rash Profuse watery diarrhea Abnormal Liver Function Test |
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What are the MAJOR sites of reaction seen in GVHD? WHY?
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Skin, Liver, GI
= they express higher levels of MHC than other tissues |
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What diseases is stem cell transplant currative?
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Diseases where the recipient's are immunodeficient:
Primary Immunodeficiency Some Leukemias Aplastic Anemia Autommune disease (Exs = SCID, Agammaglobulinemia, Hyper IgM Syndrome, Wiskott-Aldrich syndrome, Selective IgA deficiency) |
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Whats the advantage of using CORD BLOOD t oget stem cells from vs. Bone marrow or peripheral blood?
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There are NO mature T cells in cord blood = less chance of GVHD
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Whats the limitation of using cord blood as a source of stem cells?
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There's usually not ENOUGH stem cells.
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WHY does a corneal transplant NOT require immunosuppressive drugs?
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Gradt antigens don't access Lymph vessels or Nodes meaning they can't sensitize recipient's lymphocytes
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What drives immune reactions between T cells and MHC molecules?
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If T cell doesn't recognize MHC, it will attack it
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If you see MHC-A, MHC-B MHC-C, you KNOW its what type of MHC?
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MCH I
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If you see MHC-DM, MHC-DQ, MHC-DR, you KNOW its what type of MHC?
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MHC II
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THE MAJOR MHCs that predict rejection?
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MHC-A, MHC-B, MHC-DR
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Your MALE pt needs a transplant. RATE family members in order of most likely to contain compatible MHC molecules
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1. gentically identical sibling (=have SAME MHC)
2. Brother (ie same sex sibling) 3. Sister 4. dad (ie same sex) 5. mom |
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Which are better, younger or older donors? same race or does it matter?
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YOUNGer, same race
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Whats an example of a NATURAL situation that can lead to production of anti-HLA?
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pregnancy (ie fetus expressed paternal HLA thats not part of mother's HLA type) --> Anti-HLA Abs develop
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Difference between CD8 cytotoxic T cells and CD4 Helper T cells in Acute rejection?
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CD8 cytotoxic T cells = kill graft by releasing granzyme + porforin
CD4 Helper T cells = Activate macrophages by secreting inflamm cytokines These mediate BOTH acute and CHRONIC rejection, they are just INITIATED by dif. processes |
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In Chronic rejection (ie INDIRECT pathway), Recipient Dendritic cells do what? 1. present graft peptide t oCD8 T cells in the context of MHC I OR 2. present graft peptide to CD4 T cells in context of MHC II?
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present graft peptide to CD4 T cells in context of MHC II?
Vs. Acute rejection = DIRECT pathway = recipient dendritic cells present graft peptide to CH8 via MHC II OR CD4 via MHC I |
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Which, chronic or acute involves ONLY dedritic cells presenting to CD4 T cell via MHC II?
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CHRONIC
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Whats the treatment for GVHD disease?
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Give something that reduces the T cells that lead to the reaction ie T-cell depleting agent
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