Lec17 Transplan Immunology Flashcards Preview

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Flashcards in Lec17 Transplan Immunology Deck (32):
1

Isograft

- transplant to self
- identical twins
- inbred mice

2

Allograft

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

3

Xenograft

- between species [ex. pig and human]
- rapid rejection by naive mice/human

4

HLA inheritance

co-dominance because inherited as haplotypes
1 in 4 chance that new sibling will have same HLA

5

Early inflammation posttransplant

- 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

6

What are the targets of transplant immunity

- HLA
- minor histocompatibility antigens

7

What are alloreactive antibodies? How do they develop?

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

8

What are alloreactive T cells

- 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

9

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

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

10

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

minor histocompatibility antigens present other than just MHC

11

Why is male-female transplant difficult?

- 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

12

How do B cells get activated by alloantigen?

- same as normal process
- alloantigen binds BCR, get signal through IgM

13

How are T cells activated by alloantigen?

- same as normal immune response
- TCR minds MHC for signal 1, CD28/B7 and CD40L/CD40 for signal 2

14

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

- get block of T cell activation
- calcineurin is part of signalling pathway for stimulation

15

What is Il-2 role in T cell stimulation?

- released from T cell when activated
- then binds back in autocrine manner and stimulates T cell differentiation and proliferation

16

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

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

17

Effector function of alloantibodies

- 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

18

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

Block complement activtaion

19

3 Effector mech of T cells

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

20

What is thought to be pathway for acute cellular rejection?

T cells responding through direct pathway

21

What are perforin and granzyme B?

cytotoxic molec from CTL that attack allogeneic target cell

22

Is immunosuppression specific or non-specific?

Non-specific [all cells suppressed]

23

What type of cells does immunosuppression usually target?

T cells [not B cells]

24

What is most common side effect of immunosuppresion?

Infection

25

What are 4 common drugs for immunosuppression

- cyclosporine
- steroids
- sirolimus
- mycophenolate mofetil azathioprine

26

How do you diagnose acute cellular rejection?

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

27

What cells are involved in acute cellular rejection

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

28

How to treat acute cellular rejection? Is it reversible?

By increasing immunosuppresion
YES!

29

What is effect on kidney of chronic rejection?

- kidney fibrosis, develops after 2-3 yrs

30

What is thoguht to be cause of late graft failure?

- underimmunosuppresion

31

What is actively acquire tolerance of foreign cells?

- 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

32

What are 3 current methods for acquired transplant tolerance

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