Immunology

Question 1

What are the major alloantigens?

Answer 1

HLA, MHC and ABO

Question 2

What is hyperacute rejection?

Answer 2

• An immediate reaction

- caused by pre-existing antibodies against donor antigens

Question 3

Which alloantigen is most commonly an issue for hyperacute reactions?

Answer 3

ABO antigens, sometimes HLA

Question 4

What is the pathophysiological reaction that occurs during a hyperacute rejection?

Answer 4

complement activation, endothelial damage, inflammation, thrombosis

Question 5

What kind of reaction is an acute rejection?

Answer 5

• the host immune system becomes sensitized against donor antigens (HLA)
• occurs in almost all transplants

Question 6

What kind of cells are activated during an acute rejection?

Answer 6

CD4+/CD8+ T cells and macromages

Question 7

What kind of pathophysiological reaction occurs during an acute rejection?

Answer 7

Endothelialtitis
parenchymal cell damage
interstitial inflammation

Question 8

What are the characteristics of chronic rejection?

Answer 8

Host immune response against the vasculature of the donor organ occurring more than 1 year after transplantation

Question 9

What kind of cells are involved in chronic rejection?

Answer 9

CD4+ T cells

Macrophages/inflammatory cells

Question 10

What is the pathophysiological response to chronic rejection?

Answer 10

Chronic DTH reaction in the smooth muscle wall, smooth muscle cell proliferation (thickening), vessel occlusion

Question 11

Which part of a chimeric antibody are human and which are mouse/foreign?

Answer 11

Only the variable regions of the heavy and light are mouse, the rest is human antibody

Question 12

What part of a humanized antibody are human and which are mouse/foreign?

Answer 12

The only AA from the mouse are in the CDR regions of the heavy and light chain, the rest are human.

Question 13

What type of hypersensitivity reaction is serum sickness?

Answer 13

Type III

Question 14

Where can we find CD25?

Answer 14

IN the alpha chain of the IL-2 receptor

Question 15

What is the function of IL-2?

Answer 15

Growth factor for activated T cells

acts in an autocrine fashion to induce T cell proliferation

Question 16

What is the inhibitory interaction of corticosteroids?

Answer 16

They directly inhibit activated glucocorticoid receptors and activated transcription factors- NF-kB & AP-1 which regulate gene expression of inflammatory molecules

Question 17

What is the T cell activation pathway?

Answer 17

MHC binds TCR–> Increased [Ca+2}i binds calcineurin phosphatase–> dephosphorylates/activates NFAT–> NFAT enters the nucleus as a TF and induces IL-2 synthesis–>IL-2 Is synthesized and released to bind to the T cell and induce proliferation

Question 18

What are 2 immunophilins?

Answer 18

cyclophylin

FKBP

Question 19

What is the role of cyclophylin?

Answer 19

It is a petideal proleoisomerase which inhibits the CIS/trans isomerization of proline

Question 20

What drug can cyclophylin bind too?

Answer 20

Cyclosporine

Question 21

What is the function of calcineurin?

Answer 21

To dephosphorylate NFAT

Question 22

What is the function of NFAT?

Answer 22

to translocate to the nucleus and stimulate IL-2 synthesis

Question 23

What is the function of mTOR?

Answer 23

It is a protein kinase that increases the cell cycle progression of T cells, so increases growth and proliferation

Question 24

What is the role of IMPDH?

Answer 24

It is the rate limiting enzyme in the de novo synthesis of guanine nucleotides–> converts IMP to XMP

Question 25

How many kinds of IMPDH are there?

Answer 25

Two

Question 26

How do we avoid acute rejection?

Answer 26

crossmatch tests prior to transplant to identify preexisting antibodies against HLA or ABO blood groups