3 - immunosuppressants Flashcards
what are 3 reasons to use immunosuppressants
1 suppress rejection of transplanted organ (me vs you)
2 suppress graft-vs-host (you vs me)
3 auto-immune disease
what is rheumatoid arthritis
auto-immune disease mainly attacking joints
what is lupus
auto-immune disease multi organ
what is ulcerative colitis
auto-immune disease, T cell infiltration and colon ulceration
what is psoriasis
auto-immune disease leading to scaly skin patches
what drugs are similar to immunosuppressants
chemotherapy drugs
what are the 2 main phases of the immune response
induction and effector phase
which molecule in the immune response has lots of autocrine effects
IL-2 (autocrine)
who does the antigen presenter cell present to
helper T cell
what happens after helper T cell activation
activates circulating B cells (plasma or memory cells) and activates other T cells (cytotoxic, killer)
what happens in the induction phase
recognition and presentation of foreign antigen, activation and proliferation of naive Th0 cells into Th1 and Th2 cells
what do Th2 cells become
they DONT MATURE into B cells
they just activate them
what do Th1 cells become
t cells
like cytotoxic
what is the effector phase
cell mediated t cell responses (from Th1 cells)
and antibody mediated responses from B cells (from Th2 cells)
which phase do most immunosuppressant drugs affect
induction phase
what are 5 steps that are targeted by immunosuppressant drugs
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
what is the calcineurin-NFAT pathway used for
needed for the activation of naive Th0 cells and clonal expansion of T cells
what does activation of the T-cell receptor cause
generates Ca2+ signal, which activates calcineurin and dephosphorylates NFAT
what does dephosphorylated NFAT cause
leads to expression of IL2 (which is needed for activation and proliferation of T cells)
where does cyclosporine bind
cyclophilin
what does cyclosporine do
supresses calcineurin, which supressed the pathway that leads to the expression of IL2
what does tacrolimus bind
FKBP
what does tacrolimus do
supresses calineurin, which supressed the pathway that leads to the expression of IL2
how does cyclosporine and tacrolimus cause a reduction of IL2
prevents NFAT mediated gene transcription
how does rapamycin/sirolimus work
binds to FKBP which inhibits mTOR (does not inhibit calcineurin)
interferes with the downstream signals of IL2 receptor activation
what is mTOR
a major pathway responsible for promoting cell growth and proliferation
what is an example of a proliferation signal inhibitor
rapamycin/sirolimus
what do glucocorticoids do as an immunosuppressant
prevent Th cell proliferation by suppressing transcription/expression of genes for many cytokines (even IL2) and IL2 expression
reduced innate response (less complement proteins)
how do glucocorticoids effect IL 2 receptors
they dont
what are 2 cytotoxic agents
cyclophosphamide and azathioprine
how does cyclophosphamide work
cross links neighbouring bases, best in rapidly dividing cells
how does azathioprine work
it is metabolized into 6-mercaptopurine, fradulent nucleotide. this inhibits synthesis of nucleotides and interferes with cell division
what does the fab region determine
antigen specificity (where they bind, the split part, contains the variable region)
what does the Fc region determine
the antibody class (IgA, IgG, IgM, etc) (the unsplit part)
what do the different antibody classes determine
they are recognized by different receptors on different immune cell types, leading to different immune responses
what is humanization/chimerization
replacement of conserved regions of the mouse monoclonal antibody with corresponding sequence from human antibodies
the variable region is from mouse, rest human
why do humanization/chimerization
so that we dont attack the animal antibodies
how to recognize humanization/chimerization drugs
umab or imab for human or chime
what is alemtuzumab
what are its targets
humanized IgG1 that recognized CD52 found on all B and T cells, NK cells, monocytes, macrophages, grannulocytes
what is alemtuzumab used for
some leukemias, MS
what does the IgG1 Fc domain of alemtuzumab cause
recognition of it by phagocytic cells leads to cell death by lysis or phagocytosis
healthy and bad T and B cells are destroyed
what is basiliximab
what are its targets
chimeric IgG1 that binds to CD25, part of the Il2 receptor on activated lymphocyetes
how does basiliximab cause immunosuppression
by blocking IL2 from binding to activated lymphocytes
IL2 antagonist
what is graft-vs-host
when the donor stuff attacks us
how does IL-2 work (what kind of hormone effect)
autocrine
