3 - immunosuppressants

Question 1

what are 3 reasons to use immunosuppressants

Answer 1

1 suppress rejection of transplanted organ (me vs you)
2 suppress graft-vs-host (you vs me)
3 auto-immune disease

Question 2

what is rheumatoid arthritis

Answer 2

auto-immune disease mainly attacking joints

Question 3

what is lupus

Answer 3

auto-immune disease multi organ

Question 4

what is ulcerative colitis

Answer 4

auto-immune disease, T cell infiltration and colon ulceration

Question 5

what is psoriasis

Answer 5

auto-immune disease leading to scaly skin patches

Question 6

what drugs are similar to immunosuppressants

Answer 6

chemotherapy drugs

Question 7

what are the 2 main phases of the immune response

Answer 7

induction and effector phase

Question 8

which molecule in the immune response has lots of autocrine effects

Answer 8

IL-2 (autocrine)

Question 9

who does the antigen presenter cell present to

Answer 9

helper T cell

Question 10

what happens after helper T cell activation

Answer 10

activates circulating B cells (plasma or memory cells) and activates other T cells (cytotoxic, killer)

Question 11

what happens in the induction phase

Answer 11

recognition and presentation of foreign antigen, activation and proliferation of naive Th0 cells into Th1 and Th2 cells

Question 12

what do Th2 cells become

Answer 12

they DONT MATURE into B cells

they just activate them

Question 13

what do Th1 cells become

Answer 13

t cells

like cytotoxic

Question 14

what is the effector phase

Answer 14

cell mediated t cell responses (from Th1 cells)

and antibody mediated responses from B cells (from Th2 cells)

Question 15

which phase do most immunosuppressant drugs affect

Answer 15

induction phase

Question 16

what are 5 steps that are targeted by immunosuppressant drugs

Answer 16

inhibit IL2
inhibit cytokine gene expression (glucocorticoids)
cytotoxicity (kill/prevent immune cells)
inhibit nucleic acid synthesis
block T-cell surface receptors to prevent immune activation

Question 17

what is the calcineurin-NFAT pathway used for

Answer 17

needed for the activation of naive Th0 cells and clonal expansion of T cells

Question 18

what does activation of the T-cell receptor cause

Answer 18

generates Ca2+ signal, which activates calcineurin and dephosphorylates NFAT

Question 19

what does dephosphorylated NFAT cause

Answer 19

leads to expression of IL2 (which is needed for activation and proliferation of T cells)

Question 20

where does cyclosporine bind

Answer 20

cyclophilin

Question 21

what does cyclosporine do

Answer 21

supresses calcineurin, which supressed the pathway that leads to the expression of IL2

Question 22

what does tacrolimus bind

Answer 22

FKBP

Question 23

what does tacrolimus do

Answer 23

supresses calineurin, which supressed the pathway that leads to the expression of IL2

Question 24

how does cyclosporine and tacrolimus cause a reduction of IL2

Answer 24

prevents NFAT mediated gene transcription

Question 25

how does rapamycin/sirolimus work

Answer 25

binds to FKBP which inhibits mTOR (does not inhibit calcineurin) interferes with the downstream signals of IL2 receptor activation

Question 26

what is mTOR

Answer 26

a major pathway responsible for promoting cell growth and proliferation

Question 27

what is an example of a proliferation signal inhibitor

Answer 27

rapamycin/sirolimus

Question 28

what do glucocorticoids do as an immunosuppressant

Answer 28

prevent Th cell proliferation by suppressing transcription/expression of genes for many cytokines (even IL2) and IL2 expression reduced innate response (less complement proteins)

Question 29

how do glucocorticoids effect IL 2 receptors

Answer 29

they dont

Question 30

what are 2 cytotoxic agents

Answer 30

cyclophosphamide and azathioprine

Question 31

how does cyclophosphamide work

Answer 31

cross links neighbouring bases, best in rapidly dividing cells

Question 32

how does azathioprine work

Answer 32

it is metabolized into 6-mercaptopurine, fradulent nucleotide. this inhibits synthesis of nucleotides and interferes with cell division

Question 33

what does the fab region determine

Answer 33

antigen specificity (where they bind, the split part, contains the variable region)

Question 34

what does the Fc region determine

Answer 34

the antibody class (IgA, IgG, IgM, etc) (the unsplit part)

Question 35

what do the different antibody classes determine

Answer 35

they are recognized by different receptors on different immune cell types, leading to different immune responses

Question 36

what is humanization/chimerization

Answer 36

replacement of conserved regions of the mouse monoclonal antibody with corresponding sequence from human antibodies the variable region is from mouse, rest human

Question 37

why do humanization/chimerization

Answer 37

so that we dont attack the animal antibodies

Question 38

how to recognize humanization/chimerization drugs

Answer 38

umab or imab for human or chime

Question 39

what is alemtuzumab | what are its targets

Answer 39

humanized IgG1 that recognized CD52 found on all B and T cells, NK cells, monocytes, macrophages, grannulocytes

Question 40

what is alemtuzumab used for

Answer 40

some leukemias, MS

Question 41

what does the IgG1 Fc domain of alemtuzumab cause

Answer 41

recognition of it by phagocytic cells leads to cell death by lysis or phagocytosis healthy and bad T and B cells are destroyed

Question 42

what is basiliximab | what are its targets

Answer 42

chimeric IgG1 that binds to CD25, part of the Il2 receptor on activated lymphocyetes

Question 43

how does basiliximab cause immunosuppression

Answer 43

by blocking IL2 from binding to activated lymphocytes | IL2 antagonist

Question 44

what is graft-vs-host

Answer 44

when the donor stuff attacks us

Question 45

how does IL-2 work (what kind of hormone effect)

Answer 45

autocrine