Lec17 Transplan Immunology

Question 1

Isograft

Answer 1

• transplant to self
• identical twins
• inbred mice

Question 2

Allograft

Answer 2

• transplant between individuals of same species
• rapid rejection by naive mice/human
• alloimmunity from allloreactive B and T cells

Question 3

Xenograft

Answer 3

• between species [ex. pig and human]

- rapid rejection by naive mice/human

Question 4

HLA inheritance

Answer 4

co-dominance because inherited as haplotypes

1 in 4 chance that new sibling will have same HLA

Question 5

Early inflammation posttransplant

Answer 5

• ischemia and reperfersion and surgical trauma, as cell dies releases lots of antigens and creates damage associated molecular patterns [DAMPS]
• leads to ROS production, complement and TLR stimulation
• neutrophil infiltration ,organ damage
• makes organ more susceptible to immune mediated damage

Question 6

What are the targets of transplant immunity

Answer 6

• HLA

- minor histocompatibility antigens

Question 7

What are alloreactive antibodies? How do they develop?

Answer 7

• antibodies that generally recognize exposed region of MHC [HLA] molec
• develop open exposure to alloantigens during pregnancy, blood transfusion, previous transplant, or cross-reactivity

Question 8

What are alloreactive T cells

Answer 8

• CD4 and CD8 T cells recognize donor MHC
• ability to recognize donor MHC due to chance cross reactivity because recipient T cells were never trained to recognize foreign MHC molec
• by direct or indirect reognition

Question 9

Whats the difference between direct and indirect recognition of Alloreactive T cells

Answer 9

Direct: T cell binds directly to MHC + peptide presented by donor APC that it recognizes
- rxn involves donor APC/MHC/peptide and recipient T cell

Indirect: Donor antigen taken up by recipient APC and expressed on recipient APC surface for T
- rxn involves donor peptide expressed on recipient APC/MHC and recipient T cell

Question 10

What is the reason why MHC matched donor/recipient may still have graft rejection?

Answer 10

minor histocompatibility antigens present other than just MHC

Question 11

Why is male-female transplant difficult?

Answer 11

• males have some proteins made only on Y chromosome
• these are not expressed in female so female does not have tolerance to them
• if woman receives man’s you get immune reaction and rejection
• ex: Smcy, Uty

Question 12

How do B cells get activated by alloantigen?

Answer 12

• same as normal process

- alloantigen binds BCR, get signal through IgM

Question 13

How are T cells activated by alloantigen?

Answer 13

• same as normal immune response

- TCR minds MHC for signal 1, CD28/B7 and CD40L/CD40 for signal 2

Question 14

What is effect of calcineurin blocking on T cell activation in alloantigenic response?

Answer 14

• get block of T cell activation

- calcineurin is part of signalling pathway for stimulation

Question 15

What is Il-2 role in T cell stimulation?

Answer 15

• released from T cell when activated

- then binds back in autocrine manner and stimulates T cell differentiation and proliferation

Question 16

What is effect of anti-CD25 in T cell activation?

Answer 16

• anti-CD25 binds and blocks IL-2 from re-binding T cell and causing activation

Question 17

Effector function of alloantibodies

Answer 17

• anti-HLA antibody binds donor HLA on surface [type II hypersensitivity]
• Fc receptor gamma mediates binding
• get complement cascase activation
• may lose endothelial cells –> thrombosis

Question 18

How to treat antibody mediated vascularized rejection [acute or hyperacute]

Answer 18

Block complement activtaion

Question 19

3 Effector mech of T cells

Answer 19

• primed T cels produce cytokines that amplify immune response
• Delayed Type hypersensitivity [IV]: macrophage activation, release cytokins, TNF
• cytotoxicity

Question 20

What is thought to be pathway for acute cellular rejection?

Answer 20

T cells responding through direct pathway

Question 21

What are perforin and granzyme B?

Answer 21

cytotoxic molec from CTL that attack allogeneic target cell

Question 22

Is immunosuppression specific or non-specific?

Answer 22

Non-specific [all cells suppressed]

Question 23

What type of cells does immunosuppression usually target?

Answer 23

T cells [not B cells]

Question 24

What is most common side effect of immunosuppresion?

Answer 24

Infection

Question 25

What are 4 common drugs for immunosuppression

Answer 25

• cyclosporine
• steroids
• sirolimus
• mycophenolate mofetil azathioprine

Question 26

How do you diagnose acute cellular rejection?

Answer 26

• diagnosed by decrease kidney function, high serum creatinine and renal biospy

Question 27

What cells are involved in acute cellular rejection

Answer 27

• mononuclear cells
• T cells
• macrophages
• anitbodies can also contribute

Question 28

How to treat acute cellular rejection? Is it reversible?

Answer 28

By increasing immunosuppresion

YES!

Question 29

What is effect on kidney of chronic rejection?

Answer 29

• kidney fibrosis, develops after 2-3 yrs

Question 30

What is thoguht to be cause of late graft failure?

Answer 30

• underimmunosuppresion

Question 31

What is actively acquire tolerance of foreign cells?

Answer 31

• inject fetal mice with cells from other strain of mouse
• later in adulthood place skin graft from donor onto tolerized recipients
• grafts from cell donor strain last indefinietly
• grafts from another strain rejected
• only works if cells transferred in utero

Question 32

What are 3 current methods for acquired transplant tolerance

Answer 32

• give bonemarrow cells from donor along with the graft
• block costimulatory [CD28/B7] signals
• expand regulatory T cells and give them to patients