20. Transplantation Immunology

Question 1

What is an isologous (isograft) transplant?

Answer 1

Between genetically identical individuals (twins)

Question 2

What is a homologous (allograft)?

Answer 2

Shit from other individuals same species

Question 3

What is heterologous (xenograft)

Answer 3

Different species

Question 4

What are the two aspects of compatibility?

Answer 4

Physical = size (heart from child to adult etc)

Genetic

Question 5

What are the laws of transplantation immunology?

Answer 5

A - A = graft accepted

A - B = Graft rejected

B - AB = graft accepted

AB - B = Grat rejected

Question 6

What is allograft rejection caused by?

Answer 6

Adaptive immune response

Question 7

What is the process of the immune response?

Answer 7

1) Latent period
2) Memory
3) Specificity
4) Passive transfer by lymphocytes
5) Production of antibodies

Question 8

What are histocompatibility antigens?

Answer 8

Antigens that give rise to the immune response results in rejection of a tissue allograft

Question 9

What is MHC?

Answer 9

Major histocompatability complex

Question 10

What is the MHC called in humans?

Answer 10

HLA - Human leukocyte antigen

Question 11

What are Minor histocompatability Antigens?

Answer 11

mH - non MHC encoded
- Mostly single nucelotide polymorphisms
ABO
Sex chromosomes

Question 12

What is MHC called in mice?

Answer 12

H-2 complex

Question 13

Where is HLA genes located?

Answer 13

Short arm of chromosome 6

4 mill base pairs in length

Question 14

What do HLA genes code for?

Answer 14

30% of 150 expressed genes
Involved in immun response
- Complement
- Antigen processing
- Cytokines

Question 15

What are most famous members of HLA classes?

Answer 15

Class 1- HLA-A, B & C

• All nucleated cells
• Density varies from tissue to tissue

Class 2 - HLLA - DP, DQ & DR

• Antigen presenting cells
• B lymphocytes
• Activated T lymphocytes

Question 16

Do HLA have many alleles at each locus?

Answer 16

Yes

Question 17

What are the two ways in which allogenic HLA molecules are presented for T cell recognition?

Answer 17

Direct

• Recognition of intact foreign HLA molecules, presented by donor APC lelz
• Acute
• Can be controlled by immunosupression

Indirect

• Recognition of processed donor HLA molecules presented by recipient APC
• Chronic rejection
• No immunosupression

Question 18

How the feck can a recipient T cell recognise a donor APC MHC?

Answer 18

Similar structure of HLA molecules

Question 19

Can direct recognition be supressed?

Answer 19

Yes with immunosuppresion

Question 20

Can direct recognition T cells invoke memory cells immediately if donor protein/HLA looks similar?

Answer 20

Yes

Question 21

How does indirect alloantigen recognition work?

Answer 21

Allo-HLA molecule phagocytosed
Migrate to lymph
Presented on class 2

NOTE: HLA molecules are very different in structure

Question 22

Why are allo-responses so vigourous?

Answer 22

Often anti-virus secondary response that cross=react with allo-HLA molecule
- Mistakes it
- Already has memory cells ready to pwn
(Direct)

Question 23

What is hyperacute rejection?

Answer 23

Minutes, antibodies IgG

Question 24

What is accelerated?

Answer 24

2-5 days, CMI + Ab

Question 25

What is acute rejection?

Answer 25

7 - 21 days, CMI + Ab

Question 26

What is chronic rejection?

Answer 26

> 3 months CMI + Ab

Question 27

What happens in hyperacute rejection?

Answer 27

Binding to endothelium activates complement and clotting cascades Graft fills with deoxygenated blood Blood clots

Question 28

How does hyperacute rejection arise?

Answer 28

Antibodies as results of previous alloantigens - Blood transfusions - Previous transplantation - Multiple pregnancies

Question 29

How does accelerated rejection occur?

Answer 29

Low titres of alloractive antibodies alrady present, (similar to hyperacute), thus rejection develops slowly Involves cellular immune response

Question 30

How is acute rejection mediated?

Answer 30

T lymphocytes Direct pathway Humoral Antibodies Blood vessel walls Factors = clotting of graft etc

Question 31

What is chronic rejection?

Answer 31

Allo-reactive T cells secrete IFNy and TNFa Activate endothelial cells, SM and macros Secretes growth factors + chemos Acitvate smooth muscle cells Blood flow to graft blocked Parenchyma replaced by fibrous tissue

Question 32

What are pathological characteristics of chronic rejection?

Answer 32

``` Lung = thickened small airways Liver = fibrotic and non functioal bile ducts ```

Question 33

what is immunosupression?

Answer 33

Dampening down immunesystem | Avoid or delay rejection

Question 34

How do immunosupression drugs work./

Answer 34

INhibit/Kill T cells - calcineurin inhibs Metabolic toxins that kill proliferating T cells - MMF Antibodies that react with T cell surface antigens OKT3 Drugs that block co-stimulatory pathways (CTLA-4) Anti-inflammatory drugs

Question 35

What are some complications of immunosupression?

Answer 35

Vulnerable to infections Malignancies (due ot virus like CMV) - counter with Ganciclovir Development of lymphoproliferative disorders - B cell derived non-hodgkins lymphomas - BEV

Question 36

How can you reduce allograft immunogenicity?

Answer 36

Minimize alloantigenic differences ABO matching HLA compatability Screen for presence of pre-formed antibodies - Cross matching

Question 37

What HLA has strongest effect

Answer 37

HLA-DR