Term
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Definition
| transplants between menbers of the same species that differ genetically |
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Term
The HLA allows for the ability:
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Definition
- distinguish between self and non self
- provide effective immune surveillance
- identify altered or infected host cells |
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Term
what can be used to predict graft acceptance?
what are most strongly predictive? |
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Definition
- number of matched MHC loci, more loci matched, the better
-MHC Class 2, DR |
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Term
Hyper rejection: when does it occur
What mechanism is responsible for it? |
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Definition
| - recipeint antibodies that were present before the transplant attack donor antigen |
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Term
How to tell if antibodies are present in organ recipient's serum?
What is added? |
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Definition
- incubate serum with a panel of lymphocytes of known HLA specificity in individual wells. If there are HLA antibodies in the serum, they will bind to their MHC antigen on the lymphocyte cell surface.
- complement is added to the wells, lymphocytes with bound antibody will be lysed. |
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Term
| What is the principle of mixed lymphocyte culture (MLC)? |
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Definition
- Differences in class I and II antigens between the doners of the cells used in the assay will stimulate T-lympohcytes to synthesize DNA and divide.
- count number of cell divisions (as measured by newly synthesized DNA) in responder lymphocytes when exposed to irradiated stimulator lymphocytes. |
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Term
| What does an MLC require? |
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Definition
- lymphocytes from donor and recipient; one set is irradiated lymphocytes to serve as stimulator (irradiation stops them from dividing).
- radioactive precursor DNA |
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Term
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Definition
| - measure amount of radiolabled DNA taken up by responder lymphocytes |
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Term
| First step in classic rejection |
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Definition
- Dendritic cells of donor and host origin become activated and migrate to T-cell areas of secondary lymphoid organs.
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Term
how can memory cells respond during graft rejection?
How is this different from normal situations? |
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Definition
- Memory B and T cells may be activated by non-professional APC's such as endothelium of the transplanted organ
- Naive T-cells are normally optiamlly triggered by DC's in secondary lymphoid organs.
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Term
Direct pathway for activation in graft rejection
Indirect pathway for activation in graft rejection |
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Definition
Direct: activation of the immune system by the foreign MHC marker itself without any form of MHC processing or presentation
Indirect: Alloantigens are phagocytized, process and represented in the context of MHC antigens by APC's to CD4 cells. |
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Term
| What T-helper responses are involved in graft rejection, after direct or indirect activation? |
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Definition
| - usually all four! Th1,2,17 and Treg |
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Term
Which T helper pathway occurs early?
What cytokine is it dependent on? |
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Definition
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Term
| What follows Th1 activation in graft rejection? What drives it? |
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Definition
| - activation and clonal expansion of CD8 alloantigen specific T-cells driven by CD4 Th1 and Il 21. |
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Term
| what role does Th2 play in graft rejection? |
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Definition
| - Th2 will happen later and provide Il 4 and 21 for alloantigen specific B cells, which will produce antibody. |
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Term
| Cummulative effect of each pathway invovled in graft rejection (4 things) |
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Definition
1) acivated macrophage mediated graft destruction
2) CD8 antigen speific graft cytolysis
3) Th17 mediated inflammation
4) antibody mediated, graft destruction eithe rby complement or Fc receptor activation of cell death mechanisms |
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Term
| Which cell type will be most destructive if it is the dominant cell type? |
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Definition
| Th17 will be more destructive than if B cells are the dominant cell type. |
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Term
| What allows for the very broad response of graft rejection? |
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Definition
| - both donor and host dendritic cells will migrate to nearby secondary lymphoid tissue. |
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Term
| Two main steps in transplant rejection |
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Definition
1) host DC's process antigen and go to secondary lymphoid tissue, as do donor DC's
2) Th2 response in secondary lymphoid tissue causes creation of antibodies to graft; Th1 cells at graft will invoke CTL destruction of host; Th17 also involved |
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Term
| Under what two circumstance can hyperacute rejection occur? |
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Definition
- if blood groups of donor and recipient are not the same (this should never happen)
- patient has been sensitized by repeated blood transfusions or multiple pregnancies. |
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Term
| What kills a graft in hyperacute rejection? |
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Definition
- damage to its endothelium as antibodies attack it, platelet aggregation, which causes them to release vasoactive mediators taht activate coagulation and initate fibrin deposition
--> net result: graft ischemia |
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Term
| In addition to platelet aggregation, what else causes graft rejection and death? |
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Definition
| - complement system activation |
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Term
If ischemia does not kill a graft in hyperactue rejection, what will?
What results then? |
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Definition
- infiltartion by neutrophils, lymphocytes and monocytes
-> necrosis and edema |
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Term
acute rejection: when does it occur
What initiates it?
What else happens? |
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Definition
- first three weeks after grafting
- initiated by recipient CD4 T cells reacting with alloantigens (either directly or indirectly)
- CD8 cells kill, Th17 activate inflammation and B cell antibody appears |
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Term
Main characteristic of chronic rejection?
- What eventually kills the graft? |
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Definition
- widening of arterioles caused by intimal thicking
- ischemia
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Term
| What is the leading cause of retransplantation in heart transplant patients? |
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Definition
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Term
| Four strategies to prevent rejection |
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Definition
1) Optimal MHC matching (espcially locus D)
2) Blunt T-cell responses to alloantigens by immunosuppression
3) Provide inhibitory second signals (CTLA-4) or cytokines to override Th1 and CD8 response
4) Induce specific tolerance to the organ (TRegs) |
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Term
| Two situations in which graft vs. host can occur |
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Definition
1) bone marrow transplant
2) inadvertant transfusion of immunocompetent cells into a immunodeficient host |
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Term
| Antibodies to which gene product make xenotransplantation difficult? |
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Definition
| - higher primates have deleted, and thus make antibodies to alpha-1,3-GT gene |
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Term
| Three ways fetus avoids attack from mother (since half it's MHC is paternal and does match) |
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Definition
1) Fetal endothelia at interface between mother and fetus does not dipslay MHC I or II
2) Fetal tissue only displays "public" MHC-G which has an inhibitory effect on maternal NK
3) As NK's come into the uterus they are transformed into suppressive NK's |
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Term
What converts maternal NK cells to a type that will not kill fetus?
*two cytokines and a receptor |
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Definition
TGF- β
progesterone
- they do not expres CD16, an Fc receptor necessary for antibody direceted cytotoxicity |
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Term
What other cell types are increased in the uterine wall during pregnancy?
What do these secrete?
What does this inhibt? |
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Definition
δy-T cells
Tregs
- IL10, TGF-β
- Inhibits CD4 and CD8 T cell attack on the fetus. |
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Term
| Two ways complement is regulated during pregnancy? |
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Definition
- fetal trophoblasts upregulate gene complex that prevents alternate and classic complement activation by maternal anti-fetal antibodies
- Progesterone stimulates the surface cells of uterine endometrium to display CD55, complement decay factor (further inhibiting complement cell death) |
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Term
| What Th pathway will be supresed in pregnant women? which will be elevated? |
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Definition
- Th1 will be suppressed
- Th2 will be normal, TRegs will be increased |
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Term
What complement-related cell surface molecule is upregulated during pregnancy?
What step does it affect in complement? |
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Definition
- CD55
- increases decay of C3bBb0 -> C3b + Bb
- increases decay of C4bC2a -> C4b + C2a |
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Term
| What is a clinical implication for infection of a fetus? |
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Definition
| - child may build tolerance to this infection and be prevented from responding appropriately later in life |
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