4 Immunology - Lec 13 Transplant & Rejection

Front 1

A ______ graft is a Person to a genetically different recipient
A ______ graft is a One person to the same person
A ______ graft is a Person to a genetically identical recipient
A ______ graft is a Graft to a different species

Back 1

- allograft

- autograft

- syngraft

- xenograft

Front 2

What are 2 mechanisms by which grafts are recognized by recipient T-cells?

Back 2

1) recipient T cells recognize processed donor MHC peptides being presented by recipient APCs

2) recipient T cells recognize unproccessed donor MHC molecules on graft APCs

Front 3

hyperacute rejection: timing & cells involved

Back 3

- minutes or hours

- due to preformed antibodies in recipient

Front 4

acute rejection: timing & cells involved

Back 4

- 10-14 days

- due mainly to CMI but some injury is Ab mediated

Front 5

chronic rejection: timing & cells involved

Back 5

- months or years after transplant

- due to antibody, T-cells, NK cells - all attack graft

Front 6

What are 4 mechanisms of acute allograft rejection?

Back 6

1) direct contact between CD8+ cells and graft --> FasL

2) locally released cytokines & chemokines - inflammation, macrophage activation, infiltration of phagocytic cells

3) antibody against donor HLA - complement binding, ADCC

4) NK cell attack

Front 7

Stem cells can be obtained from the peripheral blood (after treatment with _________) or from umbilical cord blood or from bone marrow. What is the major problem with bone marrow transplantation?

Back 7

- colony stimulating factors

- main problem is that competent T-cells from donor may be transplanted giving rise to GVH

Front 8

Graft versus host disease (GVH)

Back 8

- A reaction of donor T-cells against recipient MHC

- CD4+ T cells activated by allogenic molecules & produce "cytokine storm" that recruits other T cells, macrophages & NK cells to create severe inflammation characteristics of GVH

Front 9

What are the 3 requirements for GVH?

Back 9

1) graft must contain live T-cells (ex bone marrow & thymus)

2) recipient must be immunosuppressed

3) donor & recipient must have different HLA types

Front 10

______ and____ block a T-cell phosphatase called calcineurin and inhibit cytokine production

Back 10

- Cyclosporine

- FK506

Front 11

________ also inhibit cytokine production and are anti-inflammatory

Back 11

- Corticosteroids

Front 12

_______ monoclonal antibody against T cells or _________ antibody to stop T cell proliferation

Back 12

- Anti-CD3

- Anti-IL-2 receptor

Front 13

alpha-fetoprotein is associated with what cancer?

Back 13

- primary hepatocellular carcinoma

- oncofetal antigen

- found on baby liver - goes away once baby matures - if person gets primary liver cancer the antigen reappears

Front 14

carcino-embryonic antigen (CEA) is associated with what cancer?

Back 14

- colon carcinoma

- oncofetal antigen

- found on fetal colon - goes away once baby matures - if person gets colon cancer the antigen reappears

Front 15

Her2/neu: what is it? what can it be treated with?

Back 15

- mutant antigen on human tumors

- if positive can be treated with perception

Front 16

Tissue specific differentiation antigen:_____ (prostate-specific antigen), B-cell (____ & ____) and T-cell markers (___, ____ or _____)

Back 16

- PSA

- CD19, CD20

- CD3, CD4, CD8

Front 17

What happens if you see a B cell population with a lot of kappa? What can they normally express?

Back 17

- you worry about a malignancy of single B cell clone

- can normally express either kappa or lambda

Front 18

Who recognizes malignant tumor cells when they lose their HLA class I?

Back 18

- they are less sensitive CD8+ cells but they will be killed by NK cells

- NK cells can recognize & are cytotoxic to HLA class I neg. cells

Front 19

Destroy infected and malignant cells with absent or defective Class I MHC (this may occur after viral infection or malignant transformation)

Back 19

- NK cells (large granular lymphocytes - LGL's)

Front 20

How do NK cells bind & kill cells without MHC I?

Back 20

- they have Fc receptors that can bind to IgG & give rise to ADCC via perforin & granzyme

- activated by cytokines IL-2, IL-12, INF gamma & produce a variety of cytokines

- they can also just bind directly & cause cytotoxicity via perforin & granzyme

Front 21

Principal mechanism of killing tumor cells is by ________ using granzyme and perforin, TNF & FasL

Back 21

- CD8

- killing can also happen by activated macrophages & NK cells

Front 22

What are 3 ways tumors can evade the immune system?

Back 22

1)They release immunosuppressive factors e.g. IL-10 and TGF-beta

2) They release factors that activate TREG cells

3) They select antigen-negative variants

Front 23

How can stimulation of innate immune mechanisms work in cancer immunotherapy? (2 drugs & their mechanisms)

Back 23

- imiquimod activates TLR7

- BCG produces inflammation in bladder wall

Front 24

What cytokines can be useful in cancer immunotherapy?

Back 24

- IL-2, IFN gamma

Front 25

what is it called when you can immunize against oncogenic viruses e.g. Hep B and HPV

Back 25

- cancer immunotherapy

Front 26

To increase immunogenicity in cancer immnotherapy you can add costimulatory molecule ____, or transfer MHC class II molecules or use cytokines

Back 26

- B7

Front 27

_______ are monoclonal antibodies attached to toxins such as ricin or radioactive isotopes. These are delivered specifically to the malignant cells to initiate direct killing.

Back 27

- Immunotoxins

Front 28

rituximab

Back 28

- targets CD20 on B-cell lymphomas

- monoclonal anti-tumor antibody

Front 29

erbitux

Back 29

- targets growth factor receptors in colon cancer

- monoclonal anti-tumor antibody

Front 30

Herceptin

Back 30

- (anti Her2/Neu) blocks growth factor signalling

- monoclonal anti-tumor antibody