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IMMUNOLOGY: CMOD-Block 2 > (18) Transplant Immunology > Flashcards

(18) Transplant Immunology Flashcards

1
Q

Define Allogenic.

A

Individuals of the same species who are genetically Different

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2
Q

What allogenic traits in humans are major determinants of transplant success or failure?

A
  • MHC class I and MHC class II genes

- Blood Group antigens

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3
Q

Define Autograft (isograft).

A

Graft of tissue from one site of an individual to another

*No rejection expected

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4
Q

Define Syngeneic Graft.

A

Graft between genetically identical patients (isograft)

*No rejection expected

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5
Q

Define allogenic graft (allograft)

A

Graft between two genetically different patients

*graft WILL be rejected unless appropriate immunosuppressive drugs are used

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6
Q

Define zenograft.

A

Graft between to individuals of different species

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7
Q

Differentiate Transplant Rejection and Graft vs. Host disease as far as when they occur.

A

Transplant Rejection:
- Solid tissue grafts are destroyed manly be T cells specific to alloantigens on grafted tissue

Graft vs. Host Disease:
- Bone marrow is transplanted into a recipient and T cells from donor marrow attack the host SKIN and GI tract mainly

***GVHD can also occur in SOLID tissue transplant IF MATURE Naive T cells are left inside the tissue

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8
Q

What is the most common type of tissue transplant?

  • what is the role of MHC?
  • Primary targets of alloreactivity?
  • Cells involved in rejection event?
A

Blood Transfusion = MOST COMMON

  • NO MHC I or II on RBCs so no worries there, ALSO MEANS NO T CELL INVOLVMENT IN REJECTION!!!!
  • Main means of alloreactivity = A and B blood group antigens
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9
Q

What is the universal Donor blood type?

  • universal recipient?
  • WHY IS THIS?
A

Universal Donor = O, Rh- antigen
Univseral Recipient = AB , Rh+ antigen

  • people with O can’t receive A or B because during development there cells were never desensitized to A and B sugar structures
  • Same goes for Rh
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10
Q

What is a major difference between the immune response to A or B antigens vs. Rh antigens?

A

A and B antigens:
- many bacteria encountered by humans have structures similar to A and B group antigens, this means that in people with O blood they will NOT ONLY have reactive B cells to A and B in there repertoire BUT they will ALSO HAVE BEEN ACTIVATED at some point previously

Rh antigens:
- Humans don’t encounter things similar to this antigen so encountering the antigen once will be NBD because we don’t have any antibodies against it

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11
Q

What is hyperacute transplant rejection and what causes it?

- how long before donated tissue is killed

A

What is it:
Rejection mediated by pre-formed antibodies that are specific for alloantigens that are expressed on grafted tissue

What causes it:

  1. VASCULAR ENDOTHELIUM HAS THE SAME A,B,O blood groups expressed that were expressed in the donors blood
  2. PRE-formed antibodies to A or B intiate complment
  3. Phagocytes come in and recognize their Fc’s and complement receptors
  4. Inflammatory Mediators cause platelet aggregation inside tissue and it dies within 48 hours
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12
Q

What two forms of tissue rejection are primarily CTL mediated?

A
  • Acute Transplant Rejection

- Minor Histocompatibility Rejection

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13
Q

Acute Transplant Rejection

  • Which Cell is Mediating?
  • What antigens cause it?
  • How long does it take, and why?
A

Cells:
- CTL’s specific for alloantigens in the grafted tissue

Antigens:

  • Alloantigens that are the product of POLYMORPHIC GENES
  • Since MHC class I and II are the most polymorphic genes in the genome it makes sense that they are THE CTL TARGET during transplant rejection

Time:
- Takes 11-15 days (w/o drug admin) because the response has to be primed after the tissue is introduced into the body

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14
Q

What is the difference between first set and second set acute transplant rejection?

  • Time?
  • Cells responsible?
  • Why does it occur?
A

1st set:

  • This is typical acute transplant rejection where the MHC’s are incompatible and it takes the host 11-15 days to mount an immune response
  • Response mediated by CTLs

2nd set:

  • This occurs if the donor donates a SECOND ROUND of the same tissue
  • Response can be mounted in 4-7 days
  • MUCH quicker because CD8 repertoire has already been built up in the 1st round
  • CTL mediated
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15
Q

T or F: in 2nd set Acute Rejection the tissue never even has a chance to become vascularized before it is killed

A

True, it the 1st round your body will allow it to become vascular before it kills the tissue, in set 2 it won’t even let this happen

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16
Q

What/whose APC’s are used to initiate the acute transplant rejection response?

A

APCs from the DONOR will migrate to 2˚ lymph tissue where it will present via MHC class I to the RECIPIENT’S Naive CD8+ cells

Since these are DONOR APCs they will be presenting a lot of donor specifc proteins (T cells in the host were never desensitized to the way that these proteins are presented on MHCs)

**Note the Recipient’s APCs can also participate in the response by taking up Donor tissue

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17
Q

What are the MHC loci that are the MOST important in assuring compatibility in a transplant?
- how do we ensure proper matches?

A
  • HLA-A
  • HLA-B
  • HLA-DR
  • Serological and DNA techniques be used to determine HLA haplotype

LONG TERM SUCCESS IS SUPER DEPENDENT ON THE DEGREE OF HLA MATCH

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18
Q

Is it possible to have a good HLA match and still see transplant rejection?

  • if so how?
  • How long would this take?
A

Yes - MHC is not the sole determinant even though its the most important

How:
Minor Histocompatibility Antigens can facilitate this response

How long:
30-60 days for response to be mounted (w/o giving any drugs)

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19
Q

Where in the genome are minor histocompatibility antigens found?

A

Encoded within the MHC locus

20
Q

What is super unique about Liver Transplantation?

A
  • IT DOES NOT REQUIRE HLA cross-matching

- Blood types DO have to match to prevent hyperacute rejection

21
Q

What matching is required for corneal transplantation?

- are anti-inflammatories used?

A
  • NO matching required because the tissue isn’t even vascularized
  • Don’t even need to use anti-inflammatories
22
Q

Why is it amazing that a fetus can live inside a mother without being rejected by the mom’s immune system?
- what are some possible explanations for this?

A

The fetus is technically and ALLOGRAFT because it contains HLA’s from the father in addition to the mother’s

No one knows why it isn’t destroyed, possible explanations:

  • Placenta is fetal tissue and does not express MHC molecules, therefore it may serve as a partial barrier to the mom’s T cells
  • Placenta and Uterine epithelium produce TH2 cytokines that down regulate cell-mediated immune response
23
Q

What is the most important of the Rh factors?

A

RhD

24
Q

What is the risk of an Rh- mother carrying an Rh+ baby?

- what disease could result?

A

If the mother is exposed to fetal blood she will mount an an immune response against that blood.

Disease:
- Erythroblastosis Fetalis - Hemolytic disease caused by IgG crossing the membrane

25
Q

Is there a risk for an Rh+ mother carrying an Rh- baby?

- what disease could result?

A

No risk here, the mom lack Rh specific Abs altogether

26
Q

Why is IgG attack on the fetus not a concern until the 2nd pregnancy usually?

A
  • In the birth of the 1st baby the Rh- mother will be exposed to a lot of the baby’s Rh+ blood during parturition and will result in her mounting an immune response to RhD
  • Since the 1st baby is out those antibodies will only be around to be encountered by a 2nd baby
27
Q

What is given to protect the second Rh+ baby that is born to an Rh- mother?
- what does it do?

A

RhoGAM - Preparation of anti-RhD IgG antibodies given to the mother following the birth of the 1st child

*anti-RhD Abs rapidly bind and cause destruction of RhD+ RBC’s preventing the mother from making an anti-RhD response

28
Q

What mediates the formation of petechial lesions in a child with Erthroblastosis Fatalis?

A

Macrophage Mediated TNF-alpha production

29
Q

What are some characteristics of a child born with Erythroblastosis Fatalis?

A
  • Enlarged Spleen and Liver from macrophages attacking RBC’s marked by Abs
  • Immune complex disease is seen in these babies because of all the antigen released when the RBCs are lysed
  • Petechial lesions are also often observed
30
Q

Who do you give RhoGAM to and why?

A

RhoGAM is given to ANY Rh- mother that gives birth because we don’t know until after the baby is born if they’re Rh+ or Rh-

**Start giving this at the beginning of the 2nd trimester

31
Q

What is the major cause of morbidity and mortality following a bone marrow transplant?

A

Graft vs. Host Disease

**Note: GVHD can take place in Solid Organ transplant but the incidence is MUCH lower than bone marrow transplant

32
Q

How does Graft vs. Host Disease play out? (step by step)

A
  1. Donor T cells were - selected for self-reactivity for DONOR not recipient
  2. Some donor T cells migrate to 2˚ lymph of the Recipient, and get activated by RECIPIENT APCs these Donor T cells then proliferate
  3. CD4 or CD8 effector cells attack the Host tissue

**This disease is Super Devastating because the Tissue is attacking the entire host, opposed to normal solid tissue rejection where just the transplanted tissue is killed

33
Q

**What are the 3 primary problems caused by Graft vs. Host Disease?

A
  1. Inflammation of the skin - MACULOPAPULAR SKIN RASH
  2. Bile duct inflammation in the liver - HIGH SERUM BILIRUBIN
  3. Damage to intestinal tract - DIARRHEA
34
Q

T or F: most organ transplants are mismatched at 1 or more HLA loci

A

True, this means we must give immunosuppressants to prevent rejection

35
Q

What is the important action of Corticosteroids that prevents transplant rejection?

A
  • Inhibits the function of NFkB, which is involved in cytokine expression

**Don’t forget it also blocks GATA-3 and HAT while upregulating HDAT

36
Q

What is the primary cytotoxic drug given to prevent graft vs. host?

A

Methotrexate

37
Q

What is the primary cytotoxic drug given following a solid organ transplant?

A

Azathioprine

38
Q

GO BACK AND REVIEW IMMUNOSUPPRESSIVE DRUGS

A

GO BACK AND REVIEW IMMUNOSUPPRESSIVE DRUGS

39
Q

What is the overall task of Cyclosporin A?

A

Prevent IL-2 expression by blocking calcineurin which is an NFAT phosphatase that leads to IL-2 transcription

40
Q

What is the job of Tacrolimus?

A

Same deal as Cyclosporin A (calcineurin inhibitor)

41
Q

What is Rapamycin, what does it do?

A

Interferes with IL-2 receptor signaling

42
Q

T or F: RBC’s express MHC class I and MHC class II molecules

A

False, RBC’s are not nucleated and don’t express MHC class I (or II), No Need for MHC I because no nucleus means CTLs can’t carry out their effector functions on these cells anyways

43
Q

T or F: Hyperacute rejection can be mediated by anti-HLA antibodies

A

True, if a patient has mounted a response against another HLA via a previous pregnancy, (blood transfusion?) or graft tissue you can run the risk of Hyperacute organ transplant rejection

44
Q

How do we assess how sensitized someone has become to a particular HLA as a result of previous exposure, that has caused them to make anti-HLA abs. that could cause Hyperacute rejection?

A

Panel-reactive Antibody (PRA) - this tests the sera of the Host against a panel of population sera and determine the Percentage of Positive reactions

***Note: this is just an antibody test for Hyperacute rejection

45
Q

A and B mismatch isn’t an issue during pregnancy, so why is Rh?

A
  • A and B are sugars that will only elicit IgM response
  • Rh is a protein that can elicit a class switching IgG response when mixed with the mothers blood (this is because a T-DEpendent response is mounted)

IMMUNOLOGY: CMOD-Block 2 (10 decks)

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