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House Clinical Pathology > IMMUNOLOGY OF TRANSPLANT REJECTION > Flashcards

IMMUNOLOGY OF TRANSPLANT REJECTION Flashcards

1
Q

Autologous grafts - Grafts transplanted from ___________ to _________ in __________

A

one part of the body

another

the same individuali

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2
Q

Syngeneic grafts (Isografts) - Grafts transplanted between __________ of —————-

A

two genetically identical individuals

the same species

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3
Q

Allogeneic grafts (Allografts) - Grafts transplanted between _________ of _____________

A

two genetically different individuals

the same species

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4
Q

Xenogeneic grafts (Xenografts) - Grafts transplanted between ________ of ————-

A

individuals of different species

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5
Q

IMMUNE RESPONSES TO TRANSPLANTED TISSUES

Transplant rejection caused by genetic differences between donor and recipient
•_______ and __________________

Alloantigens
•Antigens which _____________________________

A

HLA and blood group antigens

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6
Q

IMMUNE RESPONSES TO TRANSPLANTED TISSUES

Alloreaction
•__________ to _________

Alloreactions in transplantation
•______________ (transplant rejection)
•______________

A

Immune response; an alloantigen

Host-versus-graft

Graft-versus-host

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7
Q

Cells of Immune response to transplant

_____ Cells
____ cells
____________ cells
______ (Most important)

A

T
B

Antigen presenting

MHC

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8
Q

T cells
Arise in _____ from ______ derived precursors

Each T-Cell has a unique ___________(______)

A

thymus; bone marrow

T Cell receptor (Clone)

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9
Q

T cells

Subtypes
CD 4 T cells – ______ specific immune response

CD8 T cells - Precursors of CTL – Class ____ MHC

A

Antigen

1

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10
Q

B cells

Arise and mature in _________
Express ______ on their surface

A

bone marrow

BCRs

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11
Q

B cells

When BCR is stimulated the B cell secrete _______ of (same or different?) specificity as their BCRs

A

antibodies

Same

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12
Q

Antigen presenting cells

Most important
Activate ____ cells

They ____ antigen and _____ it on _______

A

T

Endocytose; display

MHC molecules

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13
Q

Antigen presenting cells

T cells recognize and interact with ___________ to become activated

A

antigen MHC

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14
Q

MHC complex

Encode molecules crucial to the _________ and _________ of immune response

The HLA complex on chromosome ____ contains over ____ genes

A

initiation and propagation

6; 200

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15
Q

MHC complex

The HLA genes that are involved in the immune response fall into two classes, _____ and ______, which are structurally and functionally (similar or different?)

A

I and II

Different

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16
Q

Tissue compatibility is determined by genes of the __________________

A

major histocompatibility complex

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17
Q

The MHC

In humans this is referred to as __________________ system, and are clustered on the (short or long?) arm of chromosome ____

A

Human Leucocyte Antigen (HLA)

Short; 6

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18
Q

The MHC

The HLA region is a _______genic system that encodes structurally _____logous cell surface glycoproteins that exhibit ____________

A

Multi; homo

polymorphic alleles

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19
Q

HLA class I molecules are expressed on _______________ cells

A

most nucleated

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20
Q

HLA class I:

 HLA – ____
 HLA – ____
 HLA – ____

A

A
B
C

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21
Q

HLA class II:
HLA – ____

HLA –____

HLA – ____

A

DR

DQ

DP

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22
Q

HLA class II molecules are expressed on a subset of cells of the immune system:-

______ cells, ____ cells, _________ cells, —————.

These are collectively referred to as —————- cells.

A

Dentritic

B

activated T

Macrophages

antigen presenting

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23
Q

HLA antigens
The biological function of the HLA molecules is to _____________ to T-cells, thereby playing a central role in T-cell – mediated adaptive immunity

A

present peptide antigens

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24
Q

Types of MHC
There are ______ classes of MHC molecules.

A

three

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25
Q

Types of MHC
There are three classes of MHC molecules.

Class I- encodes glycoproteins expressed on the surface of __________ cell; the major function of the class I gene is ———————- as to ————- -cells

A

nearly all nucleated

presentation of peptide antigens

cytotoxic T

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26
Q

Types of MHC
There are three classes of MHC molecules.

Class II- encodes glycoproteins expressed primarily on _______cells, examples: macrophages, dendritic cells and B-cells, where they present _____________ to ____ helper cells.

A

antigen-presenting

processed antigenic peptides

T

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27
Q

Types of MHC
There are three classes of MHC molecules.

Class III- encodes various secreted proteins that have immune function including components of the —————- ; C2,C4, Factor B, &TNF, and molecules involved in inflammation.

A

complement system

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28
Q

Function of MHC

Function of MHC
The function of both class I and class II molecules is the _______________ to _____ cells, a process that initiates the adaptive immune response

A

presentation of short, pathogen-derived peptides

T

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29
Q

Function of MHC

Class I – Detects ______ and _______ that would indicate an intracellular pathogen such as virus or intracellular bacteria; Recognised by ______ cells and provide a surveillance mechanism to target infected cells for destruction

A

cytosolic and foreign proteins

CD 8 T

30
Q

Function of MHC

Class II system is designated to sample extracellular proteins by extracellular proteins by specialized _______

Class II are recognized by ________ cells and allow for the generation of immune response to invading pathogens

A

APC’s

CD 4 helper T

31
Q

Class I

The class I genes code for the _________ of the ______ molecule

the ß chain of the class I molecule is encoded by a gene on chromosome ____, the ________ gene.

A

polypeptide chain

class I

15; beta2-microglobulin

32
Q

Class I

There are some _____ class I genes in the HLA region; three of these, _____,______ ,_______ , the so-called ______, are the main actors in the immunologic transplant reaction

A

20

HLA-A, B, and C

classic

33
Q

Class II
The class II genes code for the __________ polypeptide chains of the class II molecules .

A

alpha and ß

34
Q

Class II

The designation of their loci on chromosome ___ consists of three letters: the first (___) indicates the _____, the second (____,____,___,_____, or _____) the _______, and the third (___ or ____) the ______ ( or ____, respectively).

A

6

D; class

M, O, P, Q, or R; family

A or B; chain

ß

35
Q

Class II

HLA-DRB, for example, stands for class II genes of the R _____ coding for the ____ chains.

A

family

ß

36
Q

HLA typing
Serology:

An effective method for typing for purposes of _______

Simplicity and (low or high?) cost
Requires viable ________
Equivalent to (low or high?) resolution DNA typing

A

family donors

Low ; lymphocytes

Low

37
Q

HLA typing

Genomic DNA typing:
Based on ________ of the DNA segment

______ technology

3 levels of resolution: _____,______ and _________

A

nucleotide sequence

PCR

low, intermediate and high

38
Q

Donor

The best donor for transplant is a ————- matched ________ identified in family study

A

genotypically

sibling

39
Q

Donor

HLA-____,______,_____ (low or high?) resolution typing (2- digit DNA typing or serology) is enough to confirm genotypic identity for sibling donors.

Related donors can be identified in ____-____ % of cases

A

A,B,DR

Low

20-30

40
Q

HLA matching: Unrelated Donor

 When ________________________

 Good risk patients

 HLA-____,____,___,____,_____ – allele matched may produce comparable _______________

A

no HLA matched sibling donor is available

A,B,C,DR,DQ

disease-free survival rates

41
Q

HLA matching: Unrelated
Donor

Matched Unrelated Donor identification has been facilitated by ____________

A

Bone Marrow Worldwide Registries

42
Q

The immunology of transplant rejection

Foreign invaders are presented to the immune system in the form of small molecules called ________.

Identification of these _________ will trigger an immune response and will stimulate the production of_________ that mark infected cells for ______ by the immune system and help amplify the immune response.

A

antigens

non-self antigens

antigen specific antibodies; destruction

43
Q

The immunology of transplant rejection

The Human Leukocyte Antigen (HLA) complex is a group of genes that encode the proteins responsible for ________________________.

These proteins are found on the surface of _____ cells and act as ‘ _______ ’ telling the immune system ____________

A

identifying foreign agents to the immune system

all; self-markers

not to trigger a response.

44
Q

Mechanism of rejection

Graft rejection occurs when the ________ immune system attacks the _________ and begins ________________________.

The immune response is usually triggered by the presence of the ______’s own unique set of ________, which the recipient’s immune system will identify as _______.

A

recipient’s

donated graft

destroying the transplanted tissue or organ

donor’; HLA proteins; foreign

45
Q

Mechanism of rejection

The degree of similarity between the HLA genes of the donor and recipient is known as __________________

the more ____________ the donor and the recipient, the more ______ the recipient’s immune system should be of the graft.

A

histocompatibility

genetically compatible; tolerant

46
Q

Mechanism of rejection

However, unless the donor and recipient are __________ (e.g. as in __________) there will always be _______________.

A

genetically identical; identical twins

some degree of rejection.

47
Q

Mechanism of rejection

As well as nonself HLA proteins, other ___________ on the donor graft can also be identified as a foreign antigen and illicit an immune response.

A

surface proteins

48
Q

Graft versus host reaction’ occurs when (mature or immature?) immune cells already present in the __________ attacks the _________ of the __________.

A

Mature ; donor graft

healthy cells of the recipient

49
Q

Graft versus host reaction, where the donor graft is described as being “immune- _________” (i.e. capable of _________________________) is a particular risk with__________________ and can also occur following ___________

A

competent

producing an immune response

stem cell transplants

blood transfusions.

50
Q

Hyperacute rejection

This occurs within ______ or ______ after a transplantation and is caused by the presence of ____________________ of the recipient, that match the foreign antigens of the donor, triggering an immune response against the transplant.

These antibodies could have been generated as a result of prior _________ , prior _________ or _________.

A

minutes or hours

preexisting antibodies

blood transfusions

transplantations or multiple pregnancies

51
Q

Hyperacute rejection

The antibodies react with cells in the _______ of the graft, causing ______ to form, which will ____________ from reaching the graft resulting in immediate rejection of the transplant.

A

blood vessels

blood clots

prevent blood supply

52
Q

Acute rejection

This occurs within the first ________ after transplantation.

__________________ will occur in all transplantations, except between _________.

A

6 months

Some degree of acute rejection ; identical twins

53
Q

Acute rejection

Recipients are most at risk in the first _______, but rejection can still occur at a later stage.

A

3 months

54
Q

Acute rejection is caused by the formation of _______ following the detection of ______ antigens in the donated graft.

If diagnosed early enough, acute rejection can be treated by _______________ and permanent damage to the graft can be avoided in some cases.

A

antibodies; non-self

suppressing the immune system

55
Q

Chronic rejection

_______________ of ____ rejection can ultimately lead to chronic rejection of the graft and failure of the transplant.

A

Repeated episodes; acute

56
Q

Chronic rejection commonly manifests as ______ of the tissue or organ which can occur ______ to ________ after acute rejection has subsided.

A

scarring

months to years

57
Q

cure for chronic rejection is ????

A

At present, there is no cure for chronic rejection other than removal of the graft.

58
Q

Finding an eligible donor-recipient match

Compatibility between donor and recipient is assessed using a combination of tests, including:

ABO blood group compatibility – The donor and recipient are tested for ______________. This is the first test to be carried out as the transplant will be ___________ if the blood groups do no match.

In some transplants, for example _________ and also _______ transplants, ABO compatibility is not a necessity.

A

compatible blood groups

rapidly rejected

young children

bone marrow

59
Q

Finding an eligible donor-recipient match

Tissue typing – A blood sample is taken from the ______ to identify the ______ present on the surface of the their cells to help find a ______ ______ donor.

The more alike the HLA types of the donor and recipient are the more likely a transplant will be successful. Family members, in particular ______, are often the best HLA matches due to their genetic similarity.

A

recipient; HLA antigens

histone compatible

siblings

60
Q

Finding an eligible donor-recipient match

Cross matching – Blood samples are taken from ______________, and the _____ of the donor are mixed with the _______ of the recipient.

If the recipient’s antibodies attack the donor cells, transplantation will not be suitable due to increased risk of __________

A

both the recipient and donor

cells; blood serum

hyper-acute rejection.

61
Q

Finding an eligible donor-recipient match

Panel reactive antibody test – The ___________ of patients awaiting transplantation are tested for __________ against a __________.

Previous exposure to foreign tissue, by blood transfusion, pregnancy or prior transplantations, are likely to increase the number of ________ in the blood.

A

blood serum

reactive antibodies ; random panel of cells

HLA antibodies

62
Q

Finding an eligible donor-recipient match

Panel reactive antibody test:

The more HLA antibodies present, the (lower or higher?) the panel reactive antibody (PRA) level denoted to the patient, and the (smaller or greater?) the chance of graft rejection.

If PRA levels are high, it may be (more or less?) difficult to find a match and a higher dosage of __________ drugs may be required

A

Higher

Greater

More ; immunosuppressive

63
Q

Serology screening – For patients undergoing stem cell transplantation __________________ will undergo pre-transplant serology screening. This is undertaken to detect the _________ of both the donor and a potential recipient against a number of _____________________, including viruses like HIV, Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV), thus determining potential for __________ or _________ of the infection upon immunosuppression.

Individuals are often matched according to the _____ and _____ status.

A

they and their donor

immune status

clinically significant infectious organisms

re-infection or reactivation

CMV and EBV

64
Q

Immunosupressive drugs

To reduce the risk of transplant rejection, patients are treated with immunosuppressive drugs that will ______________________.

Immunosuppressive drugs are given in ____ phases

•an initial _______ phase involving a (low or high?) dose, and a later ________ phase which involves using the drug in the long term at a (lower or higher?) dose.

A

dampen their immune response

two

induction; high

maintenance; lower

65
Q

Immunosupressive drugs

The combination of drugs, and dosage given, will vary depending on the type of transplant and the chosen treatment regime.

If a patient experiences an episode of acute rejection, the drug combination is subject to _____ and the dosage is also likely to ____________.

_________ can also cause alternative drugs to be used.

A

change; increase

Side effects

66
Q

_______, in the past, have been the most commonly used immunosuppressant drug. However, their use is being reduced due to the ____________ associated with them.

A

Steroids

adverse side effects

67
Q

All current immunosuppressive drugs come with limitations.

One of the major limitations of these drugs is ______________.

As these immunosuppressive drugs are non-specific, they will reduce ______________ function leaving patients susceptible to opportunistic infection.

A

immunodeficiency

overall immune system

68
Q

Additionally, many of these Immunosuppressive drugs are associated with adverse side effects, such as high __________, impaired _____ function, diabetes mellitus, and increased risk of _______ – to name just a few.

Patients are required to take a (small or large?) number of immunosuppressants each day for the rest of their lives, which can have a major impact on their health and lifestyle.

A

blood pressure; renal

cancer; large

69
Q

Immunosuppressive drugs

A fine balance needs to be reached between _______________________ sufficiently to avoid rejection, preventing __________ , and maintaining __________________________.

A

suppressing immune function

drug toxicity

enough immune function to fight off disease

70
Q

Future transplant therapies

Stem cells could have a major impact on ________ in the future beyond their current use in treating ____ disorders.

Pluripotent stem cells have the capacity to mature into any cell in the body, and this ability can be harnessed to _________________.

Moreover, the discovery that other cell types can be induced to _____________ means that the cells used to make the tissue could come _______________, thus circumventing the risk of rejection.

A

transplantation; blood

grow tissues and organs

have stem cell capacities

directly from the recipient themselves

71
Q

Another future approach is the manufacture of organ scaffolds using _____________ and then __________ around these scaffolds to ____________ the tissue being replaced.

Bio- manufacturing of tissues and organs would not only ______________, if the patient’s own stem cells were used, but would also reduce the ____________________

A

3D printing

growing stem cells

artificially replicate

reduce the risk of transplant rejection

strain on the limited organ supply.

House Clinical Pathology (45 decks)

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