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Immunology Exam 2 > Transplantation Immunology > Flashcards

Transplantation Immunology Flashcards

1
Q

Prior to transplantation, tests for (1) compatibility (2) pathogens?

A
  • HLA (HLA-A, HLA-B, HLA-DR) and ABO

- HIV, Hep B, Hep C, CMV, syphilis, EBV, HTLV 1 and 2

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2
Q

Allogeneic immune responses are caused by what?

A

Differences in MHC and ABO between donor/recipient

  • donor T-cells aren’t used to recipient MHC
  • antibodies from recipient bind to donor molecules (as in ABO)
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3
Q

What is a hyperacute (immediate) reaction?

Type II hypersensitivity

A

Response to ABO (and/or MHC) expressed by endothelial cells

  • PRE-EXISTING antibodies to A/B antigen in recipients bind to the antigens on donated organs
  • also pre-existing Ab to MHC, which can come from pregnancy, blood transfusion, or previous transplantation

**Can’t be controlled

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4
Q 
Antigens / Antibodies in:
A
B
AB
O
A

A: A,O / anti-B
B: B,O / anti-A
AB: A,B,O / none
O: O / anti-A, anti-B

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5
Q

What does H enzyme do?

A

Convert precursor to ABO antigen to the H or O antigen (same thing)
- everyone has this enzyme

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6
Q

What does the A enzyme do? The B enzyme?

A

A enzyme converts O antigen to A antigen

B enzyme converts O antigen to B antigen

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7
Q

Universal donor? Recipient?

A

Donor: O RhD-

Recipient: AB RhD+

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8
Q

Which is dominant, D+ or D-?

A

D+

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9
Q

What is acute rejection?

Type IV hypersensitivity

A

Occurs within weeks; caused by effector CD4 Th1 or CD8

  • response to HLA differences
  • always some mismatch in allografts

**Can be controlled with immunosuppressive drugs / anti-T-cell antibodies

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10
Q

What is accelerated acute rejection?

A

Within days; sensitized memory T cells by previous grafts or exposure (still type IV)

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11
Q

Direct allorecognition:

Indirect allorecognition:

A
  • Donor DC presents its MHC structure / its MHC with a peptide that is recognized by recipient CD4 / CD8
  • Recipient DC presents MHC from dead donor DC
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12
Q

Direct pathway example:

A

Donor DCs to LN, recognized by T-cells, activated effector T-cells, go to target tissue (donated) and destroy

(kidney example)

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13
Q

Examine potential for graft rejection:

Mixed Lymphocyte Reaction test (MLR)

A
  • Lymphocytes, monocytes, DCs isolated from donor / recipient
  • Donor cells irradiated so they act only as stimulators, not responders
  • Mixed
  • Measure magnitude (proliferation of host cells) and killing of donor cells (capacity for graft rejection)
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14
Q

What is chronic rejection?

A

Months or years later

  • May be due to chronic DTH response?
  • T cells produce cytokines, lead to thickening of vessel due to growth of smooth muscle
  • localized tissue anemia
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15
Q

What causes (minor) MHC antigen differences in donor and recipient?

A

Polymorphic self proteins that differ in amino acid sequence between individuals

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16
Q

What is graft-versus-host disease?

A

Hematopoietic cells from transplant (T-cells) attack recipient tissues
- mostly skin, liver, intestines (tissues most damaged by chemo and radiation - most inflamed already and more susceptible)

17
Q

What is graft-versus-leukemia response? (patient with acute myelogenous leukemia)

A

Good! Donor NK cells kill recipient tumor cells based on MHC I differences

  • Haploidentical transplant (recipient has one of two inhibitory HLA-C ligands of donor)
  • Selectively kill host hematopoietic cancerous cells
  • Graft is depleted of T-cells to prevent GvHD
18
Q

For GvHD to occur:

A
  • Graft contains immunocompetent T-cells
  • MHC mismatch
  • Recipient incapable of rejecting graft
19
Q

Alternatives to minimize GvHD:

A
  • Autologous BMT (taken prior to radiation treatment)
  • Umbilical cord blood cells (less GvHD)
  • Isolated stem cells free of T-cells
20
Q

Why is T-mediated reaction often mild in xenotransplantation?

A

MHC molecules of different species are so different that human T-cells can’t recognize them; rejection is mild

**NOT always the case (Ab to pig endothelial carbohydrates, attacks by human complement, presence of a zoonosis)

21
Q

What do corticosteroids do?

A

Induce expression of anti-inflammatory genes (IkB-alpha, for example) that inhibit NF-kB activation and production of inflammatory cytokines
- So, inhibit macrophage cytokine secretion

Side effects: fluid retention, weight gain, diabetes, loss of bone mineral, thinning of skin

22
Q

What do Annexin / Lipocortins do?

A

Suppress phospholipase A2

23
Q

What does cyclosporine do?

A

Target calcineurin and block NFAT (make IL-2 for immune cell activation)

Cyclosporin : cyclophilin binding targets calcineurin

24
Q

What does tacrolimus (FK506) do?

A

Target calcineurin and block NFAT (a macrolide)
–> no cytokine production

Tacrolimus : FKBP targets calcineurin

25
Q

What does Rapamycin do?

A

Macrolide that blocks mTOR signal transduction required for lymphocyte cell proliferation (Sirolimus does this too)

26
Q

What does anti-CD3 monoclonal antibody do?

A

Deplete T cells by binding to CD3 and promoting phagocytosis or complement-mediated lysis

(Treat acute rejection)

27
Q

Cyclosporin A and Tacrolimus effects in T cells:

A
  • Less IL-2, IL-3, IL-4, GM-CSF, TNF-alpha
  • Less cell division (IL-2)
  • Less Ca-dependent exocytosis of granules
  • Inhibition of antigen-driven apoptosis
28
Q

Cyclosporin A and Tacrolimus effects in B cells:

A
  • Inhibit cell division (T-cell cytokines absent)
  • Inhibit antigen-driven cell division
  • Induce apoptosis after activation
29
Q

Cyclosporin A and Tacrolimus effects in Granulocytes:

A

Reduced Ca-dependent exocytosis of cytotoxic granules

30
Q

What does Azathioprine do?

Chemo drug

A

Inhibit DNA replication. Kill not only lymphocytes, but also all dividing cells in body: BM, intestinal epithelium, hair follicle

31
Q

What does Cyclophosphamide do?

Chemo drug

A

Cross-link DNA; side effects include damage to bladder

32
Q

What does Methotrexate do?

Chemo drug

A

Prevent DNA replication by inhibiting thymidine synthesis

33
Q

How do anti-CD3 antibodies work?

A

Derived from sheep/goats and humanized. Block signal to increase Ca in cell and downstream IL-2.
- Can induce formation of antibodies to themselves and reduce effectiveness

34
Q

Effects of corticosteroids:

A
  • Reduce IL-1, IL-3, IL-4, IL-5, GM-CSF, TNF-alpha, CSCL8 (IL-2?)
  • Reduce NOS (therefore NO)
  • Reduce Phospholipase A2 and Cyclooxygenase 2; Increase Lipcortin-1
  • Reduce cell adhesion molecules (poorer migration)
  • Induce exonucleases (apoptosis in lymphocytes and eosinophils)

Immunology Exam 2 (9 decks)

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