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immunology > L: 21 Transplantation 1 and 2 > Flashcards

L: 21 Transplantation 1 and 2 Flashcards

1
Q

Autograft

A

grafts exchanged from one part to another of the same individual

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2
Q

isograft

A

grafts exchanged between different individuals of identical genetics (identical twins)

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3
Q

Allografts

A

Grafts exchanged between nonidentical members of same species

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4
Q

Xenografts

A

grafts exchanged between members of different species

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5
Q

Problems with Xenografts

A

particularly susceptible to rapid attack by natural occurring Abs and complement. Increased chance of success if human genes are inserted into genome

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6
Q

Explain Direct Allorecognition

A

T cell recognizes unprocessed allogenic MHC molecules on graft APCs

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7
Q

Explain Indirect Allorecognition

A

T cell recognizes processed peptide of allogenic MHC molecule bound to self MHC molecule on host APC

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8
Q

In the direct pathway the T cell receptor on recipient T cells directly recognize?

A

The donor MHC molecules

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9
Q

In the indirect response the recipient T cell recognize donor MHC molecules that have been processed by?

A

Recipient APCs

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10
Q

What pathway is most important during chronic rejection

A

Indirect Pathway

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11
Q

Phases of Host vs. Graft

A

Hyperacute- immediate
Acute- week-months
Chronic- months-years
*In all cases the host has immune response to graft
**Most important thing to remember is onset time frame.

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12
Q

Graft vs. host

A

Onset varies

Donor cells proliferate and attack the recipient tissue T cells in graft

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13
Q

Hyperacute graft rejection

A

Caused by pre-existing ABs that are reactive to donor tissue AND HAPPENS WITHIN MINUTES. Abs bind to endothelial cells which activate Classical pathway of complement activation—-leads to cell death
(ABO blood group incompatibility)
ABs b

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14
Q

Acute graft rejection

A

Occurs in days to weeks and is initiated by alloreactive T cells. Donor DC’s migrate to the lymph nodes draining the organ and stimulate a primary recipient response

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15
Q

Chronic Graft Rejection

A

Occurs in months to years occurs d/t occlusion of blood vessels and subsequent ischemia of the organs.
MAIN PATHOGENIC MECHANISM is the indirect pathway.
**Chronic rejection does not respond to immunosuppressive therapy

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16
Q

Non-immunologic factors in chronic graft rejection

A
  • Ischemia-reperfusion
  • Recurrence of disease
  • Effects of nephrotoxic drugs
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17
Q

What 4 variable determine transplant outcome

A
  1. Condition of the allograft
  2. Donor-host antigenic disparity
  3. Strength of host anti-donor response
  4. Immunosuppressive regimen
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18
Q

During the Donor - Recipient work-up what is established first?

A

ABO blood group compatibility

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19
Q

ABO is a barrier to transplantation of what?

A

Solid organs

  • *Not a barrier to corneal, heart valve, and bone/tendon graft transplantations
  • *ABO incompatibility is not important to stem cel, transplant
20
Q

Group A Abs and Ags

A

ABs- anti-B

Ag- A

21
Q

Group B Abs and Ags

A

ABs- anti A

Ag - B

22
Q

Group AB Abs and Ags

A

Abs - None

Ags - A/B

23
Q

Group O Abs and Ags

A

Abs Anti- A/B

Ags - none

24
Q

What is the universal donor and recipient?

A

Universal donor- O

Universal recipient- AB

25
Q

The success of transplantation is dependent on matching of what Ags?

A 
MCH Ags
Which are encoded by MHC  class I and class II
26
Q

HLA compatibility between donor and recipient is required due to?

A

Extreme polymorphism of HLA

27
Q

In humans, the MCH is termed?

A

Human leukocyte antigen complex (HLA complex)

28
Q

Where is HLA antisera mostly obtained

A

Multiparous women or planned immunization of volunteers

29
Q

What is cross-matching used for?

A

used to test the recipient serum for preformed Abs against donor HLAss

30
Q

Why is cross-matching needed?

A

To prevent hyperactive Ab-dependent rejection of graft

31
Q

What test is used to screen for preformed Abs?

A

Microcytotoxicity test

Recipient’s serum is mixed with donors, if no cell damage, then potential donor identified. No stain=no antibodies

32
Q

What test may be used for class II HLA typing?

A

Mixed lymphocyte reaction (MLR). If class II antigens the same, no proliferation will occur. Used to determine if donor cells stimulate proliferation of recipients lymphocytes**Ags need to be the same for transplantation*Stained=same

33
Q

What is Host vs Graft response?

A

Host Immune system attacks the donor tissue

34
Q

What type of immune response occurs with Host vs Graft

A

Adaptive immune response

Rxn is much more vigorous and strong vs rxn seen against pathogen

35
Q

Effector mechanism of graft rejection- Humoral

A

Th2 (IL-4, IL-5, and IL-10)

36
Q

Effector mechanism of graft rejection-Cellular

A

Th2 (IL-2, IFN-gamma)

37
Q

Graft-Versus-Host Disease

A

occurs when transplants are small bowel, lung, or liver because of natural higher number of T cells
***Occurs in immunocompromised recipients

38
Q

A new era of transplantation and immunosuppression opened up with the discovery of what drug?

A

Cyclosporine A (CsA)

39
Q

Steroid mechanism

A

Anti-inflammatory

40
Q

Cyclosporin A mechanism

A

Inhibits IL-2 gene transcription

41
Q

Anti-CD3 monoclonal antibody mechanism (OKT 3)

A

T-cell activation, opsonization and depletion

42
Q

Tacrolimus mechanism

A

Inhibits IL-2 gene transcription

43
Q

Anti-CD25 monoclonal antibodies (IL-2R alpha chain) Sirolimus

A

Inhibits IL-2 function Inhibits cytokine-mediated signal

44
Q

What tests are done prior to transplant

A
  1. ABO blood grouping
  2. Tissue typing (identify HLAs)
  3. Cross-matching (check for pre-formed antibodies)
  4. Mixed lymphocyte reaction (check to see if donor stimulates recipient lymphocytes)
45
Q

What does the Ag-Ab complex activate?

A

Classical complement cascade which results in lymphocyte lysis

immunology (6 decks)

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