Tranfusion And Transplantation Immunology

Question 1

What is the main cause of transfusion reactions? Hyperacute graft rejection?

Answer 1

ABO incompatibilities

Question 2

What is the main cause of transplant rejection?

Answer 2

Major (HLA) and minor histoincompatibilities

Question 3

What are the characteristics of hemolytic reactions?

Answer 3

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

Question 4

What are the characteristics of febrile reactions?

Answer 4

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

Question 5

What are the characteristics of allergic/anaphylactic reactions?

Answer 5

Mediated by IgE to donor plasma proteins, including IgA
Treat with antihistamines
Epinephrine and steroids in severe cases
Anaphylaxis is rare

Question 6

What to do for IgA deficiency patient?

Answer 6

Wash RBCs to remove IgA

Question 7

What are the characteristics of transfusion associated circulatory overload (TACO)?

Answer 7

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

Question 8

What are the characteristics of transfusion related acute lung injury (TRALI)?

Answer 8

Fluid builds up in the lungs
Not related to excessive volume of transfused blood
Leading cause of transfusion related death reported by the FDA

Question 9

How is cross matching done?

Answer 9

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

Question 10

What is autograft?

Answer 10

One area to another in the same person

Question 11

What is isograft?

Answer 11

Also called syngraft

Between monozygotic twins

Question 12

What is allograft?

Answer 12

Between genetically different individuals of the same species

Question 13

What is xenograft?

Answer 13

Between different species

Question 14

What are the characteristics of first and second set rejection?

Answer 14

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

Question 15

What influence the speed of graft rejection?

Answer 15

Density of HLA molecules on surface of grafted cells

Question 16

What sensitize the recipient to the donor’s HLA?

Answer 16

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

Question 17

What are the characteristics of hyperacute rejection?

Answer 17

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

Question 18

What are the signs and symptoms of hyperacute rejection?

Answer 18

Swelling, interstitial hemorrhage 
Low blood flow
Thrombosis and necrosis
Fever and leukocytosis
Scant urine contains cells

Question 19

What are the characteristics of acute rejection?

Answer 19

Principal cause of early graft failure

2 kinds: humoral and cell-mediated

Question 20

What are the characteristics of acute humoral rejection?

Answer 20

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

Question 21

What are the characteristics of acute cell mediated rejection?

Answer 21

Occurs when doses of immunosuppressive drugs are lowered
Recipient T cells primed by passenger leukocytes attack graft
Treated by resuming immunosuppressive drugs

Question 22

What are the characteristics of chronic rejection?

Answer 22

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

Question 23

What are the TH1 role in transplant rejection?

Answer 23

secrete IL-2 and IFN gamma that stimulate Tc cells and macrophages

Question 24

What is TH2 role in transplant rejection?

Answer 24

Secrete IL-5 that stimulates eosinophilic reaction

Question 25

What is TH17 role in transplant rejection?

Answer 25

Secrete IL-17 that stimulates neutrophil mediated rejection

Question 26

What is Treg role in transplant rejection?

Answer 26

Secrete IL- 10 and TGF beta which promote graft acceptance

Question 27

What is action of cyclosporine?

Answer 27

Binds to cyclophilin to create a complex that inhibits calcineurin in T cells
Prevents IL- synthesis and IL-2R expression

Question 28

What is the action of rapamycin?

Answer 28

Inhibits IL-2R signaling in T cells by indirectly inhibiting mTOR
Does not inhibit IL-2 synthesis

Question 29

What is the action of anti-CD 25( daclizumab, basiliximab)?

Answer 29

Monoclonal antibodies bind the alpha chain of the IL-2R (CD25) expressed by activated T cells
Blocks T cell activity

Question 30

What is the purpose of hematopoietic stem cell transplantation?

Answer 30

Used to treat SCID,WAS, leukemia,thalassemia, sickle cell disease

Question 31

What are the characteristics of graft vs host disease (GVHD)?

Answer 31

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