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Year 2 Medicine > Introduction to Transplantation Immunology > Flashcards

Introduction to Transplantation Immunology Flashcards

1
Q

Syngeneic: same … background

A

Syngeneic: same genetic background

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2
Q

Allogeneic: same …, different … background

A

Allogeneic: same species, different genetic background

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3
Q

Autologous: … individual

A

Autologous: identical individual

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4
Q

Transplantation Nomenclature

  • … - to a genetically identical individual (homozygos twins) (…/syngeneic)
  • Allograft - to a genetically disparate member of the same species (allogeneic)
  • … - to another site on the same individual (e.g. after a burn) (…logous)
  • Xenograft - to a different species (pig o monkey to human) (xenogeneic)
A
  • Isograft - to a genetically identical individual (homozygos twins) (iso/syngeneic)
  • Allograft - to a genetically disparate member of the same species (allogeneic)
  • Autograft - to another site on the same individual (e.g. after a burn) (autologous)
  • Xenograft - to a different species (pig o monkey to human) (xenogeneic)
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5
Q

Transplantation Nomenclature

  • Isograft - to a genetically identical individual (homozygos twins) (iso/syngeneic)
  • … - to a genetically disparate member of the same species (…geneic)
  • Autograft - to another site on the same individual (e.g. after a burn) (autologous)
  • … - to a different species (pig o monkey to human) (…geneic)
A
  • Isograft - to a genetically identical individual (homozygos twins) (iso/syngeneic)
  • Allograft - to a genetically disparate member of the same species (allogeneic)
  • Autograft - to another site on the same individual (e.g. after a burn) (autologous)
  • Xenograft - to a different species (pig o monkey to human) (xenogeneic)
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6
Q

Transplantation Nomenclature

  • Isograft - to a genetically … individual (homozygos twins) (iso/syngeneic)
  • Allograft - to a genetically disparate member of the same … (allogeneic)
  • Autograft - to another site on the same individual (e.g. after a …) (autologous)
  • Xenograft - to a different … (pig o monkey to human) (xenogeneic)
A
  • Isograft - to a genetically identical individual (homozygos twins) (iso/syngeneic)
  • Allograft - to a genetically disparate member of the same species (allogeneic)
  • Autograft - to another site on the same individual (e.g. after a burn) (autologous)
  • Xenograft - to a different species (pig o monkey to human) (xenogeneic)
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7
Q

Transplantation Nomenclature

  • Isograft - to a genetically identical individual (… twins) (iso/syngeneic)
  • Allograft - to a genetically … member of the same species (allogeneic)
  • Autograft - to another site on the same … (e.g. after a burn) (autologous)
  • Xenograft - to a different species (pig o monkey to human) (xenogeneic)
A
  • Isograft - to a genetically identical individual (homozygos twins) (iso/syngeneic)
  • Allograft - to a genetically disparate member of the same species (allogeneic)
  • Autograft - to another site on the same individual (e.g. after a burn) (autologous)
  • Xenograft - to a different species (pig o monkey to human) (xenogeneic)
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8
Q

Nomenclature and overview - Transplantation

A
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9
Q

Nomenclature and overview - Transplantation

A
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10
Q

Warm ischemic time

  • from the interruption of … to the donor organ to the moment when organ is flushed with … preservation solution.
  • from the moment the organ is removed from the … preservation solution until the time that blood supply is reinstated.
A
  • 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.
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11
Q

Warm ischemic time

  • from the … of circulation to the donor organ to the moment when organ is … with hypothermic preservation solution.
  • from the moment the organ is removed from the cold … solution until the time that blood supply is reinstated.
A
  • 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.
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12
Q

Cold ischemic time

  • from the moment the organ is … with cold … solution until its removal from that solution.
A
  • from the moment the organ is flushed with cold preservation solution until its removal from that solution.
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13
Q

Cadaveric donor transplant

  • The transplant is from a recently … donor
  • Examples: heart, lung, pancreas, liver, kidney, cornea, limbs
A
  • The transplant is from a recently deceased donor
  • Examples: heart, lung, pancreas, liver, kidney, cornea, limbs
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14
Q

Live-related donor transplant:

  • The donor is … and … (there have been exceptions)
  • Examples: …, liver segments
A
  • The donor is alive und related (there have been exceptions)
  • Examples: kidney, liver segments
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15
Q

MHC-complex = … … complex

A

MHC-complex = Major histocompatibility complex

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16
Q

HLA is the human MHC (= … … antigen)

A

HLA is the human MHC (= human leukocyte antigen)

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17
Q

The immune response to the graft

  • How damage is caused by the OP
    • Wound healing means …
    • Warm ischemic time & cold ischemic time induce heat-… protein expression and other stress-induced molecules
    • … of ischemic organ causes … damage as a result of endothelial activation
    • In addition there will be an … response against the graft
A
  • How damage is caused by the OP
    • Wound healing means inflammation
    • Warm ischemic time & cold ischemic time induce heat-shock protein expression and other stress-induced molecules
    • Reperfusion of ischemic organ causes reperfusion damage as a result of endothelial activation
    • In addition there will be an immune response against the graft
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18
Q

The immune response to the graft

  • How damage is caused by the OP
    • Wound … means inflammation
    • … ischemic time & … ischemic time induce heat-shock protein expression and other stress-induced molecules
    • Reperfusion of ischemic organ causes reperfusion damage as a result of … activation
    • In addition there will be an immune response against the graft
A
  • How damage is caused by the OP
    • Wound healing means inflammation
    • Warm ischemic time & cold ischemic time induce heat-shock protein expression and other stress-induced molecules
    • Reperfusion of ischemic organ causes reperfusion damage as a result of endothelial activation
    • In addition there will be an immune response against the graft
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19
Q

The immune response to the graft

A
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20
Q

The immune response to the graft

  • The … recognises peptide antigen in the context of an … molecule.
  • Class-… MHC/peptide complexes are recognised by CD4, class-… MHC/peptide complexes by CD8 T-cells
  • CD4 and CD8 molecules stabilise the interaction between MHC/peptide complexes and the TCR
  • If the MHC is a ‚…‘ MHC, the complex will be recognised if it contains a ‚…‘ peptide or one that is an autoantigen.
  • The frequency of naive cells recognising ‚foreign‘ peptides is in the order of 1/10,000 to 1/100,000
A
  • The TCR recognises peptide antigen in the context of an MHC molecule.
  • Class-II MHC/peptide complexes are recognised by CD4, class-I MHC/peptide complexes by CD8 T-cells
  • CD4 and CD8 molecules stabilise the interaction between MHC/peptide complexes and the TCR
  • If the MHC is a ‚self‘ MHC, the complex will be recognised if it contains a ‚foreign‘ peptide or one that is an autoantigen.
  • The frequency of naive cells recognising ‚foreign‘ peptides is in the order of 1/10,000 to 1/100,000
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21
Q

The frequency of naive cells recognising ‚foreign‘ peptides is in the order of 1/1… to 1/1…

A

The frequency of naive cells recognising ‚foreign‘ peptides is in the order of 1/10,000 to 1/100,000

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22
Q

The immune response to the graft (2)

A
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23
Q

The immune response to the graft (3)

  • TCR interaction with a …-self class-… MHC/peptide complex is often very strong and dominated by TCR/MHC interactions.
    • It happens with donor … that are ‚passenger‘ cells in the graft.
    • This may lead to strong recipient T-cell activation requiring strong …
    • The survival time of passenger APC is limited so that … can be reduced after a few months.
A
  • TCR interaction with a non-self class-II MHC/peptide complex is often very strong and dominated by TCR/MHC interactions.
    • It happens with donor APCs that are ‚passenger‘ cells in the graft.
    • This may lead to strong recipient T-cell activation requiring strong immunosuppression.
    • The survival time of passenger APC is limited so that immunosuppression can be reduced after a few months.
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24
Q

… self proteins that differ in amino acid sequence between individuals give rise to … histocompatibility antigen differences between donor and recipient.

A

Polymorphic self proteins that differ in amino acid sequence between individuals give rise to minor histocompatibility antigen differences between donor and recipient.

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25
Q

Rejection of the graft that is mainly mediated by T-cells and occurrs within weeks to months is called … …

A

Rejection of the graft that is mainly mediated by T-cells and occurrs within weeks to months is called ACUTE REJECTION (It can be reduced/prevented by HLA-matching of donor and recipient. Antibodies developing against the donor HLA after transplantation can also make a contribution to acute rejection.)

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26
Q

Rejection of the graft that is mainly mediated by T-cells and occurrs within weeks to months is called ACUTE REJECTION (It can be reduced/prevented by …-matching of donor and recipient. … developing against the donor … after transplantation can also make a contribution to acute rejection.)

A

Rejection of the graft that is mainly mediated by T-cells and occurrs within weeks to months is called ACUTE REJECTION (It can be reduced/prevented by HLA-matching of donor and recipient. Antibodies developing against the donor HLA after transplantation can also make a contribution to acute rejection.)

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27
Q

The immune response to the graft (4)

  • Another important kind of antibody that can interfere with the graft is directed at HLA antigens. Remember that HLA is the human MHC. The text on the slide explains the mechanisms that may contribute to graft destruction.
  • The image shows a vascular cross section in a solid organ graft. Different mechanisms of graft damage are illustrated, ranging from T-cell recognising ‘non-self’ MHC to monocytes being activated by the Fc-portions of anti-HLA antibodies and P-selectin
A
  • Another important kind of antibody that can interfere with the graft is directed at HLA antigens. Remember that HLA is the human MHC. The text on the slide explains the mechanisms that may contribute to graft destruction.
  • The image shows a vascular cross section in a solid organ graft. Different mechanisms of graft damage are illustrated, ranging from T-cell recognising ‘non-self’ MHC to monocytes being activated by the Fc-portions of anti-HLA antibodies and P-selectin
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28
Q

The immune response to the graft (5)

  • Antibodies with the same coloration of the Fc region are of the same …, whereas the various colors within the F(ab’)2 denote unique antigenic specificities. (legend adapted)
  • Anti class-…MHC antibodies can induce changes in the donor vasculature, for example, causing endothelial cell (EC) activation with class-II MHC expression, and, as a result, … T cell proliferation.
A
  • Antibodies with the same coloration of the Fc region are of the same subclass, whereas the various colors within the F(ab’)2 denote unique antigenic specificities. (legend adapted)
  • Anti class-I MHC antibodies can induce changes in the donor vasculature, for example, causing endothelial cell (EC) activation with class-II MHC expression, and, as a result, CD4 T cell proliferation.
29
Q

The immune response to the graft (6)

  • Complement-activating antibodies trigger the … pathway through binding of C1q, resulting in production of the anaphylatoxins C3a and C5a, which have the potential to directly augment … recruitment and T cell …-responses.
A
  • Complement-activating antibodies trigger the classical pathway through binding of C1q, resulting in production of the anaphylatoxins C3a and C5a, which have the potential to directly augment leukocyte recruitment and T cell allo-responses.
30
Q

The immune response to the graft (7)

  • Monocytes, neutrophils, and natural killer (NK) cells also express … receptors (…), which can interact with the heavy chain of HLA antibodies bound to donor ECs. … functions augment leukocyte recruitment and mediate phagocytosis and antibody-dependent cellular cytotoxicity (ADCC).
A
  • Monocytes, neutrophils, and natural killer (NK) cells also express Fc receptors (FcγRs), which can interact with the heavy chain of HLA antibodies bound to donor ECs. FcγR functions augment leukocyte recruitment and mediate phagocytosis and antibody-dependent cellular cytotoxicity (ADCC).
31
Q

The immune response to the graft (8)

  • Activated ECs express …-selectin, which promotes recruitment of … via interactions with …-selectin glycoprotein ligand-1 (PSGL-1).
  • Recruited monocytes differentiate into CD68+ macrophages, which can infiltrate the subendothelial space.
A
  • Activated ECs express P-selectin, which promotes recruitment of leukocytes via interactions with P-selectin glycoprotein ligand-1 (PSGL-1).
  • Recruited monocytes differentiate into CD68+ macrophages, which can infiltrate the subendothelial space.
32
Q

The immune response to the graft

  • We conclude that anti-… Antibodies can severely … the graft. There are also antibodies to a range of other antigens including:
    • Red Blood Cell (RBC) antigens (mainly ABO system)
    • Endothelial Cell Antigens
  • They can also induce significant graft … We will not look at these in detail here in the interest of time. But we will come back to antibodies to RBC antigens in the next section.
A
  • We conclude that anti-HLA Antibodies can severely damage the graft. There are also antibodies to a range of other antigens including:
    • Red Blood Cell (RBC) antigens (mainly ABO system)
    • Endothelial Cell Antigens
  • They can also induce significant graft damage. We will not look at these in detail here in the interest of time. But we will come back to antibodies to RBC antigens in the next section.
33
Q
  • We conclude that anti-… Antibodies can severely damage the graft. There are also antibodies to a range of other antigens including:
    • Red Blood Cell (RBC) antigens (mainly … system)
    • … Cell Antigens
  • They can also induce significant graft damage. We will not look at these in detail here in the interest of time. But we will come back to antibodies to RBC antigens in the next section.
A
  • We conclude that anti-HLA Antibodies can severely damage the graft. There are also antibodies to a range of other antigens including:
    • Red Blood Cell (RBC) antigens (mainly ABO system)
    • Endothelial Cell Antigens
  • They can also induce significant graft damage. We will not look at these in detail here in the interest of time. But we will come back to antibodies to RBC antigens in the next section.
34
Q

The immune response to the graft

  • Very early … of the graft (minutes/hours/days) caused by antibodies to …, RBC, and EC antigens is called … ….
  • It can be prevented partially by … … and recipient …-types and … groups. There is no known way of matching for antigens recognised by anti-… antibodies as these are thought to recognise damaged … and are not donor-specific..
A
  • Very early destruction of the graft (minutes/hours/days) caused by antibodies to HLA, RBC, and EC antigens is called HYPERACUTE REJECTION. It can be prevented partially by matching donor and recipient HLA-types and blood groups. There is no known way of matching for antigens recognised by anti-EC antibodies as these are thought to recognise damaged EC and are not donor-specific..
35
Q

There is no known way of matching for antigens recognised by anti-EC antibodies as these are thought to recognise damaged EC and are not …-specific..

A

There is no known way of matching for antigens recognised by anti-EC antibodies as these are thought to recognise damaged EC and are not donor-specific..

36
Q

Preparing for a transplantation

  • …-matching – hwo good does the match have to be?
    • Minimum requirements depend on the situation
    • A kidney transplant can wait, a … cannot, a heart transplant is in between since artifical hearts can bridge the gap sometimes
    • There are some exceptions: … transplants are generally not matched as they induce chimerism., i.e. the parallel existence of two mutually tolerant immune systems (chimerism is the result of immune cells from the donor settling in the recipient‘s bone marrow and supports graft acceptance)
    • It is sometimes induced by combining … cells and organs in a transplantation
A
  • HLA-matching – hwo good does the match have to be?
    • Minimum requirements depend on the situation
    • A kidney transplant can wait, a liver cannot, a heart transplant is in between since artifical hearts can bridge the gap sometimes
    • There are some exceptions: liver transplants are generally not matched as they induce chimerism., i.e. the parallel existence of two mutually tolerant immune systems (chimerism is the result of immune cells from the donor settling in the recipient‘s bone marrow and supports graft acceptance)
    • It is sometimes induced by combining stem cells and organs in a transplantation
37
Q

Preparing for a transplantation

  • HLA-matching – hwo good does the match have to be?
    • Minimum requirements depend on the situation
    • A kidney transplant can wait, a liver cannot, a heart transplant is in between since artifical hearts can bridge the gap sometimes
    • There are some exceptions: liver transplants are generally not matched as they induce …., i.e. the parallel existence of two mutually tolerant immune systems (… is the result of immune cells from the donor settling in the recipient‘s bone marrow and supports graft acceptance)
    • It is sometimes induced by combining stem cells and organs in a transplantation
A
  • HLA-matching – hwo good does the match have to be?
    • Minimum requirements depend on the situation
    • A kidney transplant can wait, a liver cannot, a heart transplant is in between since artifical hearts can bridge the gap sometimes
    • There are some exceptions: liver transplants are generally not matched as they induce chimerism., i.e. the parallel existence of two mutually tolerant immune systems (chimerism is the result of immune cells from the donor settling in the recipient‘s bone marrow and supports graft acceptance)
    • It is sometimes induced by combining stem cells and organs in a transplantation
38
Q

… is the result of immune cells from the donor settling in the recipient‘s bone marrow and supports graft acceptance

A

Chimerism is the result of immune cells from the donor settling in the recipient‘s bone marrow and supports graft acceptance

39
Q

Preparing for a transplantation

  • HLA-matching
    • For solid organ transplantation, traditionally A,B, and DR are considered, the maximum is … mismatches (3 molecules inherited from each parent in both donor and recipient).
    • Alleles are usually not considered in … transplantation (i.e HLA-B*07:01 and HLA-B*07:02 are both HLA-B*07).
A
  • HLA-matching
    • For solid organ transplantation, traditionally A,B, and DR are considered, the maximum is 6 mismatches (3 molecules inherited from each parent in both donor and recipient).
    • Alleles are usually not considered in kidney transplantation (i.e HLA-B*07:01 and HLA-B*07:02 are both HLA-B*07).
40
Q

Preparing for a transplantation

  • HLA … matching
    • A newer approach uses antibody … predictions to analyse if a mismatch is acceptable or not. For example, a software package called ‚matchmaker‘ provides such information.
    • This approach is based on HLA sequence similarity between mismatched HLA-alleles and predicts if a mismatch is likely to give rise to an …
A
  • HLA epitope matching
    • A newer approach uses antibody epitope predictions to analyse if a mismatch is acceptable or not. For example, a software package called ‚matchmaker‘ provides such information.
    • This approach is based on HLA sequence similarity between mismatched HLA-alleles and predicts if a mismatch is likely to give rise to an antibody
41
Q

Preparing for a transplantation

  • Cross matching = … of … donor cells with recipient …
    • This is an essential test that should not be left out.
    • Subsequently, … binding is detected.
A
  • Cross matching = Incubation of washed donor cells with recipient serum.
    • This is an essential test that should not be left out.
    • Subsequently, antibody binding is detected.
42
Q

Preparing for a transplantation

A

This slide shows you, how practical tests can be performed in the lab to be absolutely sure that there are no preformed antibodies against the graft tissue in the donor.

43
Q

Advantages and disadvantages of each cross-matching method

  • … after addition of … (…-dependent …)
    • Detects only …-binding, functional antibodies
    • … sensitive, risk of false negatives (missing antibodies that cause damage but do not bind …)
  • Staining of antibodies bound to recipient cells (using mouse anti-human antibody) followed by detection by flow-…
    • Detects all … antibodies including non-functional ones or can be modified to stain complement-fixing antibodies only
    • … risk of false positives (detecting antibodies that bind but cause no damage)
A
  • Cytotoxicity after addition of complement (Complement-dependent cytotoxicity)
    • Detects only complement-binding, functional antibodies
    • Less sensitive, risk of false negatives (missing antibodies that cause damage but do not bind complement)
  • Staining of antibodies bound to recipient cells (using mouse anti-human antibody) followed by detection by flow-cytometry
    • Detects all bound antibodies including non-functional ones or can be modified to stain complement-fixing antibodies only
    • Higher risk of false positives (detecting antibodies that bind but cause no damage)
44
Q

Advantages and disadvantages of each cross-matching method

  • Cytotoxicity after addition of complement (Complement-dependent cytotoxicity)
    • Detects only complement-binding, functional antibodies
    • Less sensitive, risk of … …
  • … of antibodies bound to recipient cells (using mouse anti-human antibody) followed by detection by flow-cytometry
    • Detects all bound antibodies including non-functional ones or can be modified to stain complement-fixing antibodies only
    • Higher risk of … …
A
  • Cytotoxicity after addition of complement (Complement-dependent cytotoxicity)
    • Detects only complement-binding, functional antibodies
    • Less sensitive, risk of false negatives (missing antibodies that cause damage but do not bind complement)
  • Staining of antibodies bound to recipient cells (using mouse anti-human antibody) followed by detection by flow-cytometry
    • Detects all bound antibodies including non-functional ones or can be modified to stain complement-fixing antibodies only
    • Higher risk of false positives (detecting antibodies that bind but cause no damage)
45
Q

If an organ to be tested is not yet available, ‘panel-reactive antibodies’ may indicate the likelihood of finding a suitable organ

  • A test of the ability of recipient serum to bind to T-cells representing a group of … donors
  • An entire collection of cells with different …-types is exposed to recipient serum
  • The read-out can be based on either method shown on the previous slide
  • The multiplex method using microspheres with immobilised …-molecules is very well suited for this purpose
A
  • A test of the ability of recipient serum to bind to T-cells representing a group of potential donors
  • An entire collection of cells with different HLA-types is exposed to recipient serum
  • The read-out can be based on either method shown on the previous slide
  • The multiplex method using microspheres with immobilised HLA-molecules is very well suited for this purpose
46
Q

Preparing for a transplantation

  • How can such a response be avoided? Just like we can measure blood group antigens, we can identify HLA-antigens. It is a bit more involved than ABO typing, however. This slide shows you, how practical tests can be performed in the lab to be absolutely sure that there are no preformed antibodies against the graft tissue in the donor.
A
47
Q

Preparing for a transplantation - ‘panel-reactive antibodies

A
48
Q

Bedside testing for RBC transfusion:

  • Do you know/remember how it works?
  • A drop of fresh blood is added to each indicated section on the test card
  • Within a short time, a reaction is visible, it looks either ‘curdled’ like on the left,…or smooth like in the middle, …and curdled again, on the right
  • What is the blood group?
    • Anti-A curdled: ..
    • Anti-B smooth:..
    • Anti-D curdled: ..
A
  • Bedside testing for RBC transfusion:
    • Do you know/remember how it works?
  • A drop of fresh blood is added to each indicated section on the test card
  • Within a short time, a reaction is visible, it looks either ‘curdled’ like on the left,…or smooth like in the middle, …and curdled again, on the right
  • What is the blood group?
    • Anti-A curdled: A-antigen present
    • Anti-B smooth: B antigen absent
    • Anti-D curdled: D-antigen present
  • A-POS (RHESUS +)
49
Q

In organ transplantation the same ABO rules apply as with blood transfusion – the donor organ is similar to a red blood cell that could be … if there are antibodies to its surface antigens

A

In organ transplantation the same ABO rules apply as with blood transfusion – the donor organ is similar to a red blood cell that could be lysed if there are antibodies to its surface antigens

50
Q

ABO … is a major concern. Rhesus … is less of a worry and usually taken care of by sufficient immunosuppression.

A

ABO incompatibility is a major concern. Rhesus incompatibility is less of a worry and usually taken care of by sufficient immunosuppression.

51
Q
  • What is the chance of having an HLA-identical sibling?
  • What is the difference between an HLA-identical sibling and an HLA-identical twin?
A
  • lower part of the slide shows you the principle of HLA-gene inheritance. The chance of siblings being HLA-identical is 1:4.
  • Identical twin - identical in all genes, identical sibling only HLA, may differ with respect to other genes
52
Q

Mechanisms of graft damage - overview

A
53
Q

Chronic vascular damage

  • Antibodies to … & endothelial cell antigens entertain … cytokine production and inflammation
  • Media … & thickening of vascular wall
  • Reduction of vascular …
  • Reduced … supply
A
  • Antibodies to HLA & endothelial cell antigens entertain proinflammatory cytokine production and inflammation
  • Media proliferation & thickening of vascular wall
  • Reduction of vascular lumen
  • Reduced blood supply
54
Q

Chronic vascular damage

  • Antibodies to HLA & … cell antigens entertain proinflammatory cytokine production and …
  • Media proliferation & … of vascular wall
  • Reduction of vascular lumen
  • Reduced blood supply
A
  • Antibodies to HLA & endothelial cell antigens entertain proinflammatory cytokine production and inflammation
  • Media proliferation & thickening of vascular wall
  • Reduction of vascular lumen
  • Reduced blood supply
55
Q

Mechanisms of graft damage

  • Chronic … is a complex process and probably depends to a large extent on the damage done to the … between removal from the donor and being reperfused in the recipient.
  • Ischemic time, in particular … ischemic time seems to be a major problem.
  • But … histocompatibility antigens may also contribute, and other factors, like infection or atherosclerosis. So, it is fair to say that the process is multifactorial and there is no specific therapy to stop it.
A
  • Chronic rejection is a complex process and probably depends to a large extent on the damage done to the graft between removal from the donor and being reperfused in the recipient.
  • Ischemic time, in particular warm ischemic time seems to be a major problem.
  • But minor histocompatibility antigens may also contribute, and other factors, like infection or atherosclerosis. So, it is fair to say that the process is multifactorial and there is no specific therapy to stop it.
56
Q

Mechanisms of graft damage - overview

A
57
Q

Immunosuppression

  • … signals represent interesting target molecules for immunosuppression
A
  • Activation signals represent interesting target molecules for immunosuppression
58
Q

Immunosuppression

  • …. are probably the future (there are hundreds, some used in … transplantation are highlighted)
    • visilizumab (Nuvion)
    • eculizumab (anti-C5, Soliris)
    • adalimumab (Humira)
    • anakinra (Kineret)
    • certolizumab (Cimzia)
    • etanercept (Enbrel)
    • golimumab (Simponi)
    • infliximab (Remicade)
    • alemtuzumab (anti-CD52)
    • natalizumab (Tysabri)
    • rituximab (anti-CD20, Rituxan)
    • secukinumab (Cosentyx)
    • tocilizumab (Actemra)
    • vedolizumab (Entyvio)
    • basiliximab (anti-IL2, Simulect)
    • daclizumab (anti-CD25, Zinbryta)
A
  • Biologicals are probably the future (there are hundreds, some used in renal transplantation are highlighted)
    • visilizumab (Nuvion)
    • eculizumab (anti-C5, Soliris)
    • adalimumab (Humira)
    • anakinra (Kineret)
    • certolizumab (Cimzia)
    • etanercept (Enbrel)
    • golimumab (Simponi)
    • infliximab (Remicade)
    • alemtuzumab (anti-CD52)
    • natalizumab (Tysabri)
    • rituximab (anti-CD20, Rituxan)
    • secukinumab (Cosentyx)
    • tocilizumab (Actemra)
    • vedolizumab (Entyvio)
    • basiliximab (anti-IL2, Simulect)
    • daclizumab (anti-CD25, Zinbryta)
59
Q

Immunosuppression - Drugs

  • … inhibition
    • Cyclosporin A, Tacrolimus
    • Inhibition of cytokine synthesis: IL-2, IFNg …
  • Anti-…
    • Azathioprine, MMF
    • Inhibition of clonal expansions
  • Anti-…
    • Corticosteroids
    • NFkb inhibition, cytokine synthesis and action
A
  • Calcineurin inhibition
    • Cyclosporin A, Tacrolimus
    • Inhibition of cytokine synthesis: IL-2, IFNg …
  • Anti-proliferative
    • Azathioprine, MMF
    • Inhibition of clonal expansions
  • Anti-inflammatory
    • Corticosteroids
    • NFkb inhibition, cytokine synthesis and action
60
Q

Immunosuppression - Drugs

  • Calcineurin inhibition
    • Cyclosporin A, Tacrolimus
    • Inhibition of … synthesis: IL-2, IFNg …
  • Anti-proliferative
    • Azathioprine, MMF
    • Inhibition of clonal …
  • Anti-inflammatory
    • …steroids
    • NFkb inhibition, … synthesis and action
A
  • Calcineurin inhibition
    • Cyclosporin A, Tacrolimus
    • Inhibition of cytokine synthesis: IL-2, IFNg …
  • Anti-proliferative
    • Azathioprine, MMF
    • Inhibition of clonal expansions
  • Anti-inflammatory
    • Corticosteroids
    • NFkb inhibition, cytokine synthesis and action
61
Q

Immunosuppression

  • The biggest problem after successful transplantation is ….
A
  • The biggest problem after successful transplantation is immunosuppression.
62
Q

Corticosteroids achieve inhibition/reduction of:

  • Ischaemia/… injury
  • … activation
  • … synthesis (acute inflammation)
A
  • Ischaemia/reperfusion injury
  • APC activation
  • Cytokine synthesis (acute inflammation)
63
Q

Immunosuppression

  • Traditional view:
    • The immune system differentiates between ‘…‘ and ‘…-…‘
  • Opposing (modern) view :
    • The immune system discriminates between ‘…‘ and ‘not …‘ (while … and …-… are not important).
    • Is …-… really enough to trigger an immune response? Why is an embryo not rejected?
A
  • Traditional view:
    • The immune system differentiates between ‘self‘ and ‘non-self‘
  • Opposing (modern) view :
    • The immune system discriminates between ‘dangerous‘ and ‘not dangerous‘ (while self and non-self are not important).
    • Is non-self really enough to trigger an immune response? Why is an embryo not rejected?
64
Q

‘Self’ versus ‘non-self’

  • … also provides danger signals: trauma, inflammation, ischemia/reperfusion, etc.
  • … ischemic time is a very significant problem with respect to … survival
A
  • Surgery also provides danger signals: trauma, inflammation, ischemia/reperfusion, etc.
  • Warm ischemic time is a very significant problem with respect to graft survival
65
Q

‘Self’ versus ‘non-self’

A
66
Q

Limits of allo-transplantation

A
67
Q

Limits of allo-transplantation

A
68
Q

Limits of allo-transplantation

A

Year 2 Medicine (162 decks)

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