Tranfusion And Transplantation Immunology Flashcards
What is the main cause of transfusion reactions? Hyperacute graft rejection?
ABO incompatibilities
What is the main cause of transplant rejection?
Major (HLA) and minor histoincompatibilities
What are the characteristics of hemolytic reactions?
Result from ABO, Rh or minor blood group (Kell,Duffy, MN, Ss) incompatibilities
Usually from clerical error
Most serious kind of transfusion reactions
Type 2 hypersensitivity
Causes renal damage, DIC
Treated by stopping transfusion
What are the characteristics of febrile reactions?
Due to reactions with minor blood group antigens after repeated transfusions
Could be first sign of more serious reaction
Take seriously any temperature rise> 1 C
Type 2 hypersensitivity
What are the characteristics of allergic/anaphylactic reactions?
Mediated by IgE to donor plasma proteins, including IgA
Treat with antihistamines
Epinephrine and steroids in severe cases
Anaphylaxis is rare
What to do for IgA deficiency patient?
Wash RBCs to remove IgA
What are the characteristics of transfusion associated circulatory overload (TACO)?
Volume of transfused blood cannot be processed by patient
Too high infusion rate/or volume
Underlying heart or kidney condition
Difficulty, breathing, cough, fluid on lungs
What are the characteristics of transfusion related acute lung injury (TRALI)?
Fluid builds up in the lungs
Not related to excessive volume of transfused blood
Leading cause of transfusion related death reported by the FDA
How is cross matching done?
Donor cells are mixed with recipient serum
If there is agglutination: do not perform transfusion- recipient has IgM to donpr ABO antigens
Donor cells and mixed with recipient serum and anti human IgG (Coombs test)
If agglutination: do not perform transfusion
What is autograft?
One area to another in the same person
What is isograft?
Also called syngraft
Between monozygotic twins
What is allograft?
Between genetically different individuals of the same species
What is xenograft?
Between different species
What are the characteristics of first and second set rejection?
Graft rejection shows both specificity and memory
First set rejection occurs in 10-14 days
2nd set rejection occurs faster due to presence of memory CD4 and CD8 T cells
What influence the speed of graft rejection?
Density of HLA molecules on surface of grafted cells
What sensitize the recipient to the donor’s HLA?
Most immunogenic cells are the donor dendritic cells Also called passenger leukocytes Leave graft and take up residence in lymph nodes Rich in both class 1 and 2 HLA
What are the characteristics of hyperacute rejection?
Occurs within a few minutes to a few hours of transplantation
Mostly due to ABO incompatibilities
Type 2 hypersensitivity
No therapy, graft will be lost
What are the signs and symptoms of hyperacute rejection?
Swelling, interstitial hemorrhage Low blood flow Thrombosis and necrosis Fever and leukocytosis Scant urine contains cells
What are the characteristics of acute rejection?
Principal cause of early graft failure
2 kinds: humoral and cell-mediated
What are the characteristics of acute humoral rejection?
Antibody mediated Within first week after transplantation Rapid organ function decline Donor specific antibody and complement component C4d Enlarged, tender kidney Fall in urine output Rise in serum creatinine level Treat with corticosteroids, Rituximab and/or plasmapheresis
What are the characteristics of acute cell mediated rejection?
Occurs when doses of immunosuppressive drugs are lowered
Recipient T cells primed by passenger leukocytes attack graft
Treated by resuming immunosuppressive drugs
What are the characteristics of chronic rejection?
Progressive loss of function over months to years
Antibodies and complements cause vasculitis ( type 3 hypersensitivity)
CD4 T cells activate additional cell types (type 4 hypersensitivity)
Fibrosis and scarring
Return of original problem
No useful therapy
What are the TH1 role in transplant rejection?
secrete IL-2 and IFN gamma that stimulate Tc cells and macrophages
What is TH2 role in transplant rejection?
Secrete IL-5 that stimulates eosinophilic reaction
What is TH17 role in transplant rejection?
Secrete IL-17 that stimulates neutrophil mediated rejection
What is Treg role in transplant rejection?
Secrete IL- 10 and TGF beta which promote graft acceptance
What is action of cyclosporine?
Binds to cyclophilin to create a complex that inhibits calcineurin in T cells
Prevents IL- synthesis and IL-2R expression
What is the action of rapamycin?
Inhibits IL-2R signaling in T cells by indirectly inhibiting mTOR
Does not inhibit IL-2 synthesis
What is the action of anti-CD 25( daclizumab, basiliximab)?
Monoclonal antibodies bind the alpha chain of the IL-2R (CD25) expressed by activated T cells
Blocks T cell activity
What is the purpose of hematopoietic stem cell transplantation?
Used to treat SCID,WAS, leukemia,thalassemia, sickle cell disease
What are the characteristics of graft vs host disease (GVHD)?
Acute causes 15-40% of HCT mortality
Chronic occurs in up to 50% of HCT patients that survive after 3 months
Present with enlarged spleen, liver, lymph nodes
Skin rash
Severe diarrhea and weight loss
Autoimmunity hemolytic anemia
