Transplants

Question 1

When are transplants needed

Answer 1

Irreversible organ damage End-stage organ failure Alternative methods are not working or can not be applied

Question 2

What are some routine transplants

Answer 2

RBC, stem cells Skin grafting for burn victims Kidney heart and liver

Question 3

Host vs Graft disease

Answer 3

Differences in major HLA Ag High frequency if T cells recognizing HLA on graft T cells recognize minor HLA ag

Question 4

Graft vs host

Answer 4

Donor lymphocytes attack graft recipient Requires removal of T cell from graft often seen in BM transplants

Question 5

How are donor-recipient compatibility tested?

Answer 5

ABO blood typing Tissue typing Tissue cross matching

Question 6

Tissue Typing

Answer 6

HLA must match Tested by serological tests via microlymphocytotoxicity test PCR of HLA-DR/DQ genes HLA I- A, B, C HLA II- DQ, DP, DR

Question 7

Tissue cross matching

Answer 7

Determines if recipient has antibodies aginst donor WBC Cytotoxic and flow cytometry testing to see if recipient has IgG Abs to donor leukocytes

Question 8

What are the main ways immunosuppresive drugs work

Answer 8

Block immune response to transplant Affect T cell function Affect both T and Bcells

Question 9

What are the 4 ways that drugs can effect T cells?

Answer 9

Calcineurin inhibitors Inhibitors of T cell activation and proliferation Anti T cell immunoglobulins IL-2 receptor antagonists

Question 10

Calcineurin Inhibitor Mechanism

Answer 10

• Inhibit calcineurin enzyme
• Inhibit activation of transcription factor NFAT in T cells
• Blocks transcription/production of IL-2
  
  • Without IL-2 T cells arent stimulated
  • Blocks the IL-2 dependent growth and diffferntiation of T cells

Question 11

Examples of Calcineurin Inhibitors

Answer 11

Cyclosporine

Tacrolimus

Inhibit calcineurin, NFAT, IL-2

Prevents stimulation, growth, differentiation of T cells

Question 12

Mechanism drugs inhibit T cell activation and proliferation

Answer 12

Inhibits enzyme mTOR

Inhibits IL-2 driven proliferation of T cells

Question 13

Drugs that inhibit T cell activation and proliferation

Answer 13

Sirolimus

Rapammycin

Inhibit IL-2 signaling

Question 14

Anti T cell immunoglobulin mech

Answer 14

Antibodies that bind T cells

Question 15

Antithymocyte globulin

Answer 15

Non-specific

Can bind T cells, B cells, platelets, leukocytes

Question 16

Murononab (OKT3)

Answer 16

Specifically binds CD3 on T cell

Blocks TCR signaling

Depletes all circulating T cells via:

Complement activation

Opsonization-phagocytosis of T cells

Question 17

IL-2 receptor Antagonists Mech

Answer 17

Bind to IL-2 receptor on activated T cells

Secreted IL-2 can’t bind

No T cell proliferation

Question 18

IL-2 recptor antagonist drugs

Answer 18

Daclizumab

Bisilixmab

Question 19

What are the 2 groups of drugs that affect T cells and B cells?

Answer 19

Antimetabolites

Corticosteroids

Question 20

Antimetabolite mechanism

Answer 20

Inhibition of purine synthesis in lymphocytes

Prevents lymphocyte precursor proliferation

All are purine analogs which block cell division

Question 21

Antimetabolite drugs

Answer 21

Azathioprine

Mycophenolate mofetil

Question 22

Corticosteroids mechanism

Answer 22

Inhibits PLA2 –> decreased synthesis of prostaglandins and leukotrienes

Decreased prostaglandins –> decreased inflammation and T cell migration

Decreased leukotrienes –> decreased inflammation, chemotaxis, degranulation of OMNs and CTL proliferation

In short: Reduce inflammation by inhibiting macrophage cytokine secretion

Question 23

Corticosteroid Drugs

Answer 23

Prednisone

Methylprednisone

Suppress humoral and cell-mediated immune response

Very effective