MHC in human populations

Question 1

what causes death by neglect of T cells in thymic selection?

Answer 1

TCR and MHC+ self antigen has no binding

Question 2

what causes T cell positive selection?

Answer 2

When there is a moderate signal between a TCR and MHC with self peptide bound

Question 3

what causes negative selection of an autoreactive T cell?

Answer 3

When the signal between a TCR and MHC with self antigen bound to very strong

Question 4

how many MHC isotypes do each individual express?

Answer 4

Express 3 different isotypes of MHC-I
Express 3 different isotypes of MHC-II

Question 5

what are the most important MHC classes to match in transplants?

Answer 5

HLA-A
HLA-B
HLA-DR

Question 6

what are the different types of MHC-I?

Answer 6

HLA-A
HLA-B
HLA-C

Question 7

what are the different types of MHC-II?

Answer 7

HLA-DR
HLA-DP
HLA-DQ

Question 8

what restricts host MHC?

Answer 8

Polymorphic MHC molecules and T cell restriction to host MHC is the basis for alloreaction/transplant rejection

Question 9

what is indirect transplant rejection?

Answer 9

Low level MHC in the graft leads to slow graft rejection

Question 10

what is acute graft rejection?

Answer 10

A short period of time due to direct immune rejection

Question 11

what is chronic graft failure?

Answer 11

over a long period of time

Question 12

what is challenging for Maori transplantation?

Answer 12

Challenging finding transplant donors for bone marrow transplant and for kidney transplant amongst Maori

• DIffering attitudes to cultural appropriateness of tissue donation/transplantation amongst whanau

Question 13

what does coexpression of MHC mean for conservation of different MHC?

Answer 13

Recessive MHC cannot be bread out

Question 14

how do HLA antibodies affect transplants?

Answer 14

they can cause rejection
- arise following pregnancy, transfusions, previous transplantations, or cross-reaction with pathogen/commensal structures

Question 15

how do ABO blood antigen antibodies affect transplants?

Answer 15

Arise from stimulation from oligosaccharides on gut commensal bacteria

Question 16

what is pre-transplant screening?

Answer 16

Donors that might cause a reaction with host anti-MHC / anti-AB graft-reactive antibodies eliminated by pre-transplant screening

Question 17

what are the steps when host antibodies reject grafts?

Answer 17

1. Pre-existing host antibodies are carried to kidney graft
2. Antibodies bind to antigens of renal capillaries and activate complement
3. Complement split products attract neutrophils, which release lytic enzyme
4. Neutrophil lytic enzymes destroy endothelial cells; platelets adhere to injured tissue, causing vascular blockage

Question 18

what is the process of acute rejection of a kidney graft through the direct pathway of allorecognition?

Answer 18

1. Kidney graft with dendritic cells
2. Dendritic cells migrate to the lymph node and sleep via the blood, where they activate effect T cells
3. Effector T cells migrate to graft via blood
4. Graft is destroyed by effector T cells

Question 19

what is direct antigen presentation during transplant rejection?

Answer 19

Involves recognition of donor MHC by recipient T cells

Question 20

what is indirect antigen presentation during transplant rejection?

Answer 20

Indirect involves presentation of minor histocompatibility antigens (donor specific antigens) bu host APC and recognition by host T cells

Question 21

what is graft versus host disease?

Answer 21

• Allogeneic hematopoietic cell transplant contains mature and memory T cells
• T cells circulate in blood to secondary lymphoid tissues. Alloreactive cells interact with dendritic cells and proliferate
• Effector CD4 and CD8 T cells enter host tissues and cause injury