Transplant Immunology

Question 1

What is an autograft and isograft and how are they tollerated

Answer 1

Autograft- taken from one part of body

Isograft- taken from one indv with same genome

generally well tolerated

Question 2

What is an allograft and xenograft and how are they tolerated

Answer 2

Allograft- one indv who is not genetically identical

Xenograft- graft from another species

Subject to rejection (non self)

Question 3

What are the antigens primarily responsible for tolerance/rejection

Answer 3

MHC molecules (your haplotype)
ABO antigens

Question 4

What are the characteristics of MHC molecules (3)

Answer 4

1. polygenic (several different MHC genes- HLA A, HLA B..)
2. Polymorphic (many different alleles for HLA genes)
3. Expressed codominantly from each parent

Question 5

Where are MHC I/II expressed and how many genes encode for each

Answer 5

MHC I- on most nucleated cells and encoded by a single gene

MHC II- Occurs on APCs and are encoded by 2 genes

Question 6

What is alloreactivity

Answer 6

Response to alloantigens (non self antigens)- non self MHC antigens

T cells usually selected against this during pos selection but 10% persist

Question 7

What are examples of immunosuppressive drugs (3)

Answer 7

1. Corticosteriouds (pressione)
2. Cytotoxic drugs (interfere w DNA synthesis in cells that divide quick such as lymphocytes)
3. Drugs that interfere w t cell signalling

Question 8

What is allo reactivity and what are the types (3)

Answer 8

T cell response

1. direct alloregignition
2. Indirect alloregignition
3. Semi direct allo regigniton

Question 9

What occurs in direct alloregigntion

Answer 9

-Donar APCs leave graft and activate recipient t cells

T cells become activated as TCR and interact w allo MHC

Activated T cells (CD8 and CD4) migrate to graft causing damaging cytotoxic/ inflammatory responses

Question 10

What occurs in indirect allorecognition

Answer 10

• Host APCs pick up donor antigens
• Host APCs migrate to peripheral lymphoid organs and activate alloreactive t cells (host)
• activated t cells migrate to graft leading to damage

Question 11

What occurs in semi direct allorecognition

Answer 11

non self MHCs are expressed on surface of recipient APCs which are then used to activate recipient alloreactive T cells

Question 12

What are the 3 main types of graft rejection

Answer 12

Hyperacute rejection- Antibody mediated
Acute rejection- t cell/antibody mediated
Chronic rejection- T cell> antibody responses

Question 13

Hyperacute rejection- timeline, how

Answer 13

within 24 hrs

• Mediated by pre existing alloantibodies in the recipient that target MHC/ ABO antigens in grafts vasculature
• activate classic complement pathway, clots form

Question 14

Acute rejection- timeline, how

Answer 14

• weeks to months

- Mostly t cell mediated- infiltrate into graft and cause inflammatory damage to tissue parenchyma

Question 15

Chronic rejection- timeline, how

Answer 15

• eventually all grafts- years after
• Delayed type IV hypersensitivity- alloreactive Th1 cells infiltrate graft vessels and activate macrophages leading to inflammation and intimal thickening

Question 16

What is a tertiary lymphoid organ

Answer 16

Abnormal lymph node like structures that form in peripheral tissues at sites of chronic inflammation such as transplanted organs undergoing graft rejection

Question 17

What are the 2 types of hematopoietic stem cell transplanatation

Answer 17

Aurologous- self bone marrow

Heterologous- where a non related humans stem cell is donated

Question 18

what do HSCT preparations usually contain and what does it do

Answer 18

contain alloreactive graft t cells which may attack recipient
-epithelial apoptosis