Micro Transplants Flashcards
what are the most critical antigens to match in transplantation?
blood groups
what are the three major classes of rejection
hyperacute, acute, chronic
what is a potential problem when bone marrow is transplanted?
graft T-cells react with host tissues (graft vs host disease) - need to remove T-cells from transplant
hyperacute rejection
most severe and immediate type of rejection caused by preformed antibodies that react to the transplanted organ - MC is blood group antigen
can also have pre-existing antibodies against HLA-antigens
what is a way that pre-existing antibodies against HLA-antigens can be formed already?
past blood transfusion - other person’s WBC could already be making those antibodies
graft rejection when blood group antigens don’t match
pre-existing antibodies against donor blood group antigens, antibodies bind vascular endothelium of graft, initiating an inflammatory response that occludes blood vessels -> graft becomes engorged and purple-colored because of hemorrhage causing graft failure
what is the panel reactive antibodies?
serum of a recipient is tested against a panel of leukocytes and determines the presence of antibodies to HLA - presented as a percentage from 0-100%
- low value = antibody against a few individuals
- high value = high likelihood that patient will have antibodies against potential donor tissue
antibodies to paternal HLA - problems for pregnancy
trauma of birth exposes maternal circulation to fetal cells and stimulates the production of antibodies against paternal HLA - future pregnancies at risk
acute rejection
T-cells from the recipient become reactive against the transplant - takes days to weeks
what are most rejections due to MHC focused on?
class I mismatches which lead to CD8+ cells killing transplanted cells
what are the two mechanisms of acute rejection?
- stronger response: response to donor cells expressing class II MHC
- activated CD8+ lymphocytes kill based on MHC class I mismatches
mechanism by which kidney graft destroyed by effector T cells
dendritic cells from kidney graft migrate tot eh spleen where the activate effector T cells, and then effector T cells migrate to graft via blood
HLA class I isotypes
HLA-A, B, C, E, F, G
HLA class II isotypes
HLA-DM, DO, DP, DQ, DR
what is direct allorecognition?
both CD4 and CD8 positive cells are stimulated at the same time
chronic rejection
takes months to years - the result of indirect recognition of the transplant (only CD4 or minor antigens)
what is chronic rejection often associated with?
the presence of antibodies to HLA-class I antigens in the graft which act on the vasculature - increasing damage to vessels
what testing is done to make transplants work?
- blood type (ABO)
- HLA I and II
- panel reactive antibody
- find match on computer net
- cross match on all positive sera from antibody screening
- mixed lymphocyte reaction
- molecular techniques
what does the mixed lymphocyte reaction measure?
the ability of recipient cells to respond to donor MHC antigens (proliferation vs cytotoxicity)
what gives rise to minor histocompatibility antigen differences between donor and recipient
polymorphic self proteins that differ in amino acid sequence between individuals
how is rejection prevented?
induction of immunosuppression at time of transplant
- inducing sever immunosuppression at the time of transplant
- antilyphocyte globulin (ALG or ATG)
- monoclonal antibodies
- belatacept (CTLA4-IG)
antilymphocyte (thymocyte) globulin (ALG or ATG)
a preparation that contains antibodies raised in rabbits or horses directed against T cells
monoclonal antibodies used in prevention of rejection
- muromonab-CD3 - (anti-CD3) - bind CD3 molecule on surface of T cells and eliminates T cells
- daclizumab and basiliximab target IL-2 (CD25) inhibiting only activated T cells
belatacept (CTLA4-IG)
a protein produced by recombinant DNA technology that combines the extracellular portion of CTLA4 - ligand for B7 - with the Fc region of the human IgG1 antibody, blocking co-stimulation of T-cells
what are used for life long maintenance treatments?
maintenance drugs
- corticosteroids - interfere with transcription factor needed to turn on the genes for T cells to become activated - usually use prednisone and prednisolone
- cytotoxic drugs
- FK506 and cyclosporine
cytotoxic drugs in life long maintenance treatments
interfere with DNA synthesis - interfere with the rapid cell proliferation needed for immune responses
-azathioprine (purine analog) - MC use mycophenolic acid
FK506 and cyclosporine in life long maintenance treatments
naturla products isolated from microbial cultures - inhibit the calcineurin signaling pathway used by T cells to turn on their genes for activation (IL-2 secretion)
- FK506 = prograf
- cyclosporine = neoral
grade I tissue reaction for graft vs host
- maculopapular rash on less than 25% of body surface
- serum bilirubin 2-3 mg
- more than 500 ml diarrhea per day
grade II tissue reaction for graft vs host
- maculopapular rash on 25-50% body surface
- serum bilirubin 3-6 mg
- more than 1000 ml diarrhea per day
grade III tissue reaction for graft vs host
- generalized erythroderma
- serum bilirubin 6-15 mg
- more than 1500 ml diarrhea per day
grade IV tissue reaction for graft vs host
- generalized erythroderma with bullous formation and desquamation
- serum bilirubin at 15 mg
- severe abdominal pain with or without ileus
graft vs host disease is most likely to happen with?
class I and II mismatch, and class II mismatch
lowest survival long term is associated with what?
class I and II mismatch and multiple class I mismatch
