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KMMS > MSI Transplant Immunology > Flashcards

MSI Transplant Immunology Flashcards

1
Q

What is an example of an immune-privileged site of transplantation?

A

Corneal transplants can be accepted by the donor without any evidence of rejection d/t the fact that there is no vascularisation and no way for the immune cells to reach the cornea.

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2
Q

In vascularised solid organ transplants, these are sites with a good blood supply so that the immune system can reach them, it is absolutely necessary for genetically similar donors to be screened, and therefore reduce the risk of …

A

rejection

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3
Q

Bone marrow transplants or haematopoietic transplants which are similar to vascular solid organ transplants. In these cases, the patients are heavily immunocompromised, so they will develop a higher risk of …

A

graft vs host disease

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4
Q

Transplant between genetically identical individuals (homozygos twins) (iso/syngeneic)

A

Isograft

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5
Q

Transplant between genetically disparate member of the same species (allogeneic)

A

Allograft

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6
Q

Transplant to another site on the same individual (e.g. after a burn) (autologous)

A

Autograft

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7
Q

Transplant to a different species (pig or monkey to human) (xenogeneic)

A

Xenograft

Most common example of this is pig valves for heart valve replacement

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8
Q

** What is the most common type of transplantation?

A

Allograft

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9
Q

The response of the recipient’s immune system against the donor’s. The foreign Ags and the T lymphocytes are the main players in this response.

A

Host vs graft dz

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10
Q

Immune responses such as host vs graft in allogeneic organs and tissues is a mainly __________ dependent process.

A

T cell

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11
Q

In allogeneic haematopoietic stem cell (ie bone marrow) transplant, the types of immune responses that can occur include both ….

A

Host vs graft and graft vs host disease

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12
Q

The time from the interruption of circulation to the donor organ to the moment when organ is flushed with hypothermic preservation solution.
from the moment the organ is removed from the cold preservation solution until the time that blood supply is reinstated.

A

Warm ischemic time

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13
Q

The time from the moment the organ is flushed with cold preservation solution until its removal from that solution.

A

Cold ischemic time

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14
Q

A transplant that is from a recently deceased donor

Examples: heart, lung, pancreas, liver, kidney, cornea, limbs

A

Cadaveric donor transplant

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15
Q

A transplant were the donor is alive and related (there have been exceptions)
Examples: kidney, liver segments

A

Live-related donor transplant

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16
Q

What step should be taken to prevent organ allograft rejection between identical twins?

A

HLA matching is required to ensure that no immune response will happen

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17
Q

** What is the standard of care for prevention of organ allograft rejection?

A

Immunosuppressive drugs

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18
Q

“The Holy Grail of Transplantation” is to be able to induce immune __________ without causing any serious complications to the recipient or the organ

A

tolerance

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19
Q

A genetic locus that we have to think about when we consider any type of genetic transplant is the ___ antigens, which can be extremely polymorphic

A

HLA

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20
Q

** The effects of_________ mismatchesare the most important in the first 6 months after transplantation

A

HLA-DR

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21
Q

** Which genes illicit the strongest responses by T cells and antibodies in transplant rejections?

A

HLA antigens

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22
Q

Transplants with the highest amount of genetic mismatches had the __________ lifespan of the organ

A

shortest

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23
Q

** The effects of which genes are the most important when we consider transplant matching?

A

HLA DR

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24
Q

What is the most important effector of rejection?

A

MHC- BY FAR

Others include T cells (with antigen MHC to become activated)
B cells
Antigen presenting cells (Activate T cells
Endocytose antigen and display it on MHC molecules)

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25
Q

** What are the main targets for rejection in response to allografts?

A

Major Histocompatibility antigens (MHC Class I) which are expressed on all nucleated cells

And MHC Class II antigens found on B cells, APC, Monocytes/macrophages

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26
Q

Encode molecules crucial to the initiation and propagation of immune response

A

HLA (or MHC) complex

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27
Q

What process initiates the adaptive immune response?

A

The presentation of short, pathogen-derived peptides to T cells via the MHC complex

28
Q

This class of MHC complex samples cytosolic proteins and detect foreign proteins that would indicate an intracellular pathogen such as virus or intracellular bacteria

A

MHC class I

29
Q

What type of T cells recognise MHC class 1 antigen presentation?

A

Recognised by CD 8 T cells and provide a surveillance mechanism to target infected cells for destruction

30
Q

This MHC class system is designated to sample extracellular proteins by specialized APC’s

A

MHC class II

31
Q

What type of T cells recognise MHC class II antigen presentation?

A

Class II are recognized by CD 4 helper T cells and allow for the generation of immune response to invading pathogens

32
Q

Recognition of Alloantigens by T cells: _______ recognition of MHC alloantigens on donor cells: intact MHC molecules displayed by cells in the graft are recognised by recipient T cells without a need for processing by host APCs.

A

Direct

33
Q

Recognition of Alloantigens by T cells: _______ recognition of Alloantigens: donor (allogeneic) MHC molecules are captured and processed by Recipient APCs, and peptides derived from the allogeneic MHC molecules are presented in association with Self MHC molecules

A

Indirect

34
Q

Which pathway of all-recognition (direct or indirect) is most important in the immediate post-transplant period?

A

The direct pathway is very important in the immediate post-transplant period, as without appropriate immuno suppression, a strong and effective allo-response would follow, which is primarily d/t a high number of recipient T cells that will recognise the graft Ags and cause an acute cellular rejection.

35
Q

Which pathway of allo-recognition is predominantly seen in late onset/chronic rejection?

A

indirect

36
Q

** HLA differences between donor and recipient activate numerous alloreactive T cells. The anti-____ alloresponse is stronger than any ordinary immune response.

A

MHC

37
Q

Key Steps in T cell Activation:

APC must process and present peptides to T cells
T cells must receive a costimulatory signal
(Usually from _________)
Accessory adhesion molecules help to stabilize binding of T cell and APC:
CD4/MHC-class II or CD8/MHC class I
LFA-1/ICAM-1
CD2/LFA-3
Signal from cell surface is transmitted to nucleus
(Second messengers)
Cytokines produced to help drive cell division
(IL-2 and others)

A

CD28/B7

38
Q

Effector functions of Alloreactive T cells (CD4 and CD8) and B cells activated are activated by graft alloantigens cause rejection by distinct mechanisms:

CD8 CTLS that are generated by direct allorecognition of donor MHC molecules on donor APCs can recognize the same MHC molecules on parenchymal cells in the graft and kill those cells by CTL -mediated killing of graft cells.
CD 8 CTLs that are generated by the pathway are self MHC restricted, and they will not be able to kill the foreign graft cells because these cells do not express self MHC alleles displaying allogeneic peptides.
both CTLs and helper T cells generated by either direct or indirect alloantigen recognition cause cytokine-mediated damage to grafts.
the principal mechanism of rejection is __________ caused by the cytokines produced by the effector T cells.

A

inflammation

39
Q

Activation of Alloreactive B Cells and Production and Functions of Alloantibodies:

\_\_\_\_\_\_\_\_\_\_ against graft antigens also contribute to rejection.
Most high-affinity alloantibodies are produced by helper T cell–dependent activation of alloreactive B cells, much like antibodies against other protein antigens(donor HLA molecules, including both class I and class II MHC proteins).
Engage effector mechanisms, including complement activation, and targeting and activation of neutrophils, macrophages, and NK cells through Fc receptor binding.
A

Antibodies

40
Q

What are the four types of allograft rejection?

A

Hyperacute (Ab-mediated)
Acute vascular (Ab-mediated)
Acute cellular
Chronic (Ab-mediated)

41
Q

Types of allograft rejection: _______
Larger component of indirect recognition, resulting in activation of CD 4 T cells that induce rejection mainly by triggering cytokine mediated inflammation, and by helping B cells to make antibodies against alloantigens

A

Chronic (antibody-mediated)

42
Q

What is a common example of hyperacute rejection?

A

ABO blood group mismatch

43
Q

What is the pathology involved in a hyperacute rejection reaction?

A

Pre-existing recipient antibodies lead to a THROMBOTIC OCCLUSION in the graft vasculature leading to ischaemia, denaturation, and necrosis of the transplanted organ

44
Q

What is the pathology involved in a hyperacute rejection reaction?

A

Pre-existing recipient antibodies lead to a THROMBOTIC OCCLUSION in the graft vasculature leading to ischaemia, denaturation, and necrosis of the transplanted organ
(ie Antibodies against donor blood group antigens bind to endothelial cells and fix complement, initiating an inflammatory response that occludes blood vessels)

45
Q

Organ transplantation involves procedures that inflame the donated organ and the transplant recipient, activating innate immunity

This type of transplant rejection is caused by effector CTL cells responding to HLA differences and minor histocompatibility antigens between donor and recipient and killing of graft cells

A

Acute Cellular Rejection

46
Q

Acute Cellular Rejection is a __ cell mediated process

A

T

47
Q

Which type of transplant rejection involves preformed antibodies?

A

Hyperacute rejection

48
Q

The mechanism of this type of rejection reaction involves T-cells and anti-HLA antibodies formed in response to the graft. Develops over weeks, months, or longer.

A

acute rejection

49
Q

Antibodies formed to major and minor histocompatibility antigens describes which type of rejection reaction?

A

chronic rejection

50
Q

Cells primarily responsible for indirect pathway?

A

CD4 T helper

51
Q

** Lifelong ___________ Drugs are the standard of care in Organ transplantation

A

immunosuppressive

52
Q

How are immunosuppressive drugs prescribed after organ transplantation?

A

Given in two phases- initial induction phase (high dose immunosuppression), and then later a lower maintenance dose

53
Q

** Cytotoxic drug used in immunosuppression to kill proliferating cells

A

Azathioprine

54
Q

** MOA of Cyclosporin?

A

Calcineurin inhibitor

55
Q

** Which immunosuppressant drug selectively inhibits T cell activation?

A

Cyclosporin

56
Q

What class of drugs inhibits NFkb, cytokine synthesis and action?

A

Corticosteroids

57
Q

What type of transplant is Used to treat genetic diseases of blood-forming cells and haematological malignancies?

A

Haematopoeticcell transplantation (HCT) (aka bone marrow transplant)

58
Q

When grafted tissue has mature T cells, they will attack host tissue leading to _________
Major problem for bone marrow transplant
Affects epithelial tissues (skin, intestinal system, liver)

A

graft v host reaction

59
Q

Why is Graft v host dz is more common in bone marrow transplant patients?

A

because the recipient is immunocompromised

60
Q

Prevention of GVHD
T cell depletion – increased rejection and increased relapse risk, immunodeficiency
HCT as immunotherapy for cancer – depends on alloreactivity (T cells +/- NK cells)
Other strategies:
_____________ drugs
Immunomodulation
Post-transplant cyclophosphamide
Cytokines administered or blocked
T regs, Th1/Th2, adhesion molecule and chemokine blockade
Epithelial growth factors
Rituximab (cGVHD)

A

Immunosuppressive

61
Q

The biggest problem after successful transplantation is

A

immunosuppression

62
Q

Serum of potential recipient is incubated with cells from possible donor

If recipient has anti-donor antibodies there is a strong likelihood that recipient would destroy transplant by antibody mediated rejection

This describes what type of test?

A

Cross matching test

63
Q

Patients awaiting organ transplants are screened for the presence of _________ _________ reactive with allogeneic HLA molecules. These can arise because of previous pregnancies, transfusion, or transplantation & can mediate hyperacute graft rejection if they exist

A

preformed antibodies

64
Q

In cases where a living donor may be used for tissue transplantation, tissue-typing to match the ___ antigens of the recipient & donor is needed. Routine HLA typing focuses only on HLA-A, HLA-B, & HLA-DR

A

HLA

65
Q

What types of testing is performed in preparation of transplantation?

A

Blood typing and ABO compatibility
HLA typing
Mixed lymphocyte reaction (MLR) for T-helper cell activation
Screening for pre-formed antibody and crossmatching

KMMS (58 decks)

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