Transplant immunity

Question 1

What are the Class I and Class II MHC alleles

Answer 1

Class I: HLA-A, B,C

Class II: HLA-DR,DQ,DP

Question 2

Which MHC proteins have limited polymorphism and appear to be less important

Answer 2

HLA-C and HLA-DP

Question 3

What is Direct vs. Indirect Alloantigen recognition?

Answer 3

Direct is when the T cell recognizes unprocessed allogeneic MHC molecule on graft APCs.

Indirect is when the T cell recognizes processed peptide of allogeneic MHC molecule bound to self MHC molecule on host APC

Question 4

What involves the recognition of minor histocompatibility antigens?

Answer 4

Hematopoietic stem cell transplants

Question 5

Define Autologous

Answer 5

Self. Used in the context of hematopoietic transplants from self. (not used in the context of organ transplants)

Question 6

Define Allogeneic

Answer 6

Another individual within the same species.

Question 7

Define Xenogeneic

Answer 7

From another species.

Question 8

Define Chimerism

Answer 8

A mixture of donor and recipient cells. So in an organ allograft situation, this would apply. You have donor cells going into recipient.

Question 9

What are the 3 types of rejection

Answer 9

1. Hyperacute-Not commonly seen, but major barrior to xenotransplantation;occuring within minutes.
2. Acute-Occurs within days or weeks in non-immune suppressed individuals or months or years in suppressed individuals. May be cellular or humoral in nature.
3. Chronic- Major cause of graft failure (as treatments for acute have improved). Occurs within months/years; Primarily involves CD4+ T cells making cytokines, activating macrophages resulting in pro-inflammatory cytokines and growth factors influencing cell smooth muscle proliferation resulting in vessel occlusion in the allograft.

Question 10

How is graft rejection prevented?

Answer 10

Immunosuppressive drugs:

Cyclosporine is one of the main ones

Question 11

How are Hematopoietic Stem Cell Transplantations used? (HSCT)

Answer 11

Therapy for hematopoietic and nonhematopoietic malignancies (like aplastic anemia and immune deficiencies).

Question 12

How is HSCT or Hematopoietic Stem Cell Transplantation done?

Answer 12

Obtained from bone marrow or peripheral blood after mobilization by GF or chemokine receptor inhibitors or umbilical cord blood.

Recipient treated with chemotherapy and/or irradiation to eliminate malignant cells or diseased hematopoietic cells.

Incoming HSCs are administered IV because the Hematopoietic stem cells home to the vacant bone marrow niche based on chemokine gradients Cxcl12 and Sdf1 are the main ones

Question 13

What are Minor Histocompatibility Antigens (miHA)?

Principal determinant?

Other main points?

Answer 13

Cleaved and processed endogenous proteins that occupy the binding groove of MHC class I and class II molecules.

Genetic polymorphism is the principal determinant as to whether a self peptide can be a miHA.

Can be MHC I or II restricted. Cumulative in their effect on rejection (as in multiple minor=major). Hierarchical

Question 14

What are some of the immune problems associated with transplantation of allogeneic Hematopoietic Stem Cells?

Answer 14

Finding a suitable donor with histocompatibility

Graft vs. Host disease (acute and chronic)

Risk for infection

Graft rejection

Malignant disease relapse

Slow immune recovery

Question 15

What is graft vs. host disease?

Answer 15

Incoming donor T cells recognize host cells causing, attack tissues of the recipient host, cause

Question 16

What is GVHD staged on?

Answer 16

Extent of involvement of key target tissues: Skin, Liver, GI tract

on a scale of 1-4

Question 17

What is the mixed lymphocyte reaction?

Answer 17

Way in culture of measuring alloreactivity, mimicking in vivo. Not important diagnostic test but important assay for looking at donor host antigen reactivity