Immunotherapy Flashcards
Activation of the TCR results in increased intracellular levels of this ion
Ca2+
TCR activation without CD28 costimulation results in this
Anergy
Ca2+ dependent phosphatase that dephosphorylates NFATc
Calcineurin
Calcineurin dephosphorylates this transcription factor, which is inactive and sequestered in the cytoplasm when phosphorylated
NFATc
Calcineurin is activated by this
Increased intracellular Ca2+ from TCR activation
NFATc is a transcription factor that leads to activation of genes encoding this
Cytokines (specifically IL-2)
IL-2 binding to its IL-2 receptor on T cells leads to activation of this, which causes cell cycle progression and promotes T cell division and proliferation
mTOR
mTOR is activated by this
IL-2 binding to its receptor on T cells
Big 4 adverse effects for monoclonal antibodies
Hypersensitivity
Increased risk of infections
Increased risk of heart failure
Increased risk of cancer
Chimeric monoclonal anti-CD20 Ag on B cells
Depletes B cells, reduces Ab production
Rituximab
Rituximab is a monoclonal antibody for this
Anti-CD20 antigen on B cells
Rituximab depletes these cells
B cells
Chimeric monoclonal antibody to the alpha subunit (CD25) of the IL-2 receptor on activated T cells
Inhibits T cell activation and proliferation
Basiliximab
Basiliximab is a chimeric monoclonal antibody to this
Alpha subunit (CD25) of the IL-2 receptor on activated T cells
Basiliximab inhibits activation/proliferation of these cells
T cells
Fatal infusion reactions and fatal multifocal leukoencephalopathy are adverse effects of this
Rituximab
GI upset, hypersensitivity, increased risk of infection, heart failure, and cancer are adverse effects for this
Basiliximab
Polyclonal, recombinant, cytotoxic antibodies to surface T cells antigens
Indicated for induction and to terminate transplant rejection
Anti-thymocyte globulin
Anti-thymocyte globulin is indicated for these 2 things
Induction and to terminate transplant rejection
Immunosuppression, hypersensitivity, fever and chills, hypotension, increased risk of cytomegalovirus infections are adverse effects of this
Anti-thymocyte globulin
Hypotension from anti-thymocyte globulin can be minimized by pretreatment with these
Corticosteroids, acetaminophen, or antihistamines
Pretreatment with corticosteroids before treatment of anti-thymocyte globulin can minimize this adverse effect
Hypotension
Corticosteroid pretreatment can minimize hypotension as a result of this drug
Anti-thymocyte globulin
Class of drugs that cause the death and redistribution of lymphocytes by curtailed activation of NF-kB
Inhibit synthesis of pro-inflammatory cytokines
Glucocorticoids
Glucocorticoids curtail the activation of this, resulting in increased apoptosis of lymphocytes
NF-kB
NF-kB activation can be curtailed by these drugs
Glucocorticoids
3 Indications for glucocorticoids
Prevent and treat transplant rejection
Auto-immune disorders
Allergic reactions to other immunosuppressive agents
Increased risk of infections such as oral candidiasis and adrenal suppression are adverse reactions to this
Glucocorticoids
Drug used for induction and to terminate transplant rejection
Anti-thymocyte globulin
Drug used to prevent and treat transplant rejection, auto-immune disorders, and allergic reactions to other immunosuppressive agents
Glucocorticoids
2 adverse reactions to glucocorticoids
Increased risk of infections such as oral candidiasis
Adrenal suppression
2 calcineurin inhibitors
Tacrolimus and Cyclosporine
Protein that binds tacrolimus
FKBP-12 (FK binding protein)
Blocks calcineurin’s phosphatase activity; blocks IL-2 production
Protein that binds cyclosporine
Cyclophilin
Blocks calcineurin’s phosphatase activity; blocks IL-2 production
Both calcineurin inhibitors (Tacrolimus and cyclosporine) binds to this
An immunophilin (chaperone protein)
FKBP-12 (FK binding protein) binds tacrolimus
Cyclophilin binds cyclosporine
2 drugs that block calcineurin’s phosphatase activity, preventing movement of NFAT, and blocking the production of IL-2
Calcineurin inhibitors - Tacrolimus and Cyclosporine
4 adverse effects to calcineurin inhibitors (Tacrolimus and Cyclosporine)
Renal toxicity
Cardiovascular risk elevated by hyperlipidemia
Hypertension
Hyperglycemia/diabetes (especially when combined with glucocorticoids)
Renal toxicity, cardiovascular risk elevated by hyperlipidemia, hypertension, and hyperglycemia are adverse effects to this type of drug
Calcineurin inhibitors
FKBP-12 is an immunophilin (chaperone) that binds this drug
Tacrolimus
Cyclophilin is an immunophilin (chaperone) that binds this drug
Cyclosporine
Tacrolimus and Cyclosporine primarily act on these cells
T cells
Are calcineurin inhibitors; Block the production of IL-2
Nephrotoxicity, neurotoxicity, elevated cardiovascular risk, and hyperglycemia are adverse effects of this
Tacrolimus (calcineurin inhibitor)
4 toxicities of Tacrolimus
Nephrotoxicity
Neurotoxicity
Cardiovascular risk
Hyperglycemia/diabetes
Widely used immunosuppresive drug that can treat dry eye
Cyclosporine (calcineurin inhibitor)
Renal toxicity, cardiovascular risk, hypertension, hyperglycemia/diabetes, and hepatotoxicity are adverse effects to this
Cyclosporine
5 toxicities to Cyclosporine
Renal toxicity (important to monitor renal function through BUN/creatinine, CrCl)
Cardiovascular risk
Hypertension
Hyperglycemia/diabetes
Hepatotoxicity
Sirolimus and Everolimus bind this, which complexes with mammalial target of rapamycin (mTOR) to block progression of cell cycle in T cells
FKBP-12
Drugs that bind FKBP-12 and complexes with mTOR to block progression of cycle cycle in T cells
Sirolimus and Everolimus
Sirolimus and Everolimus ultimately block this
mTOR –> block progression of cell cycle in T cells
2 drugs that inhibit the response to IL-2 but do not alter its production
Net effect is blocked cell proliferation
Sirolimus and Everolimus
Hyperlipidemia, renal failure, hyperglycemia, angioedema, and bone marrow suppression are adverse effects to these
Sirolimus and Everolimus
5 adverse effects to Sirolimus and Everolimus
Hyperlipidemia
Renal failure (especially when combined with cyclosporine)
Hyperglycemia
Angioedema
Bone marrow suppression
2 anti-proliferative / anti-metabolic drugs
Azathioprine and Mycophenolate mofetil
Azathioprine is first converted to this
Then to false/decoy nucleotides that incorporate into RNA to block translation
Mercaptopurine (anticancer drug)
Drugs that bind FKBP-12, that complexes with mammalian target of rapamycin (mTOR) to block progression of cell cycle in T cells
Sirolimus and Everolimus
Drug that is converted first to mercaptopurine (anticancer drug) and then to false/decoy nucleotides that incorporates into RNA to block translation
Powerful anti-inflammatory action
Azathioprine
2 adverse effects of Azathioprine
Bone marrow suppression and increased risk of infections
Azathioprine ultimately blocks this
Translation; inhibits T cell function more than B cell function
(Converted first to mercaptopurine (anticancer drug) and then to false/decoy nucleotides that incorporates into RNA to block translation)
Allopurinol inhibits biotransformation of this drug, increasing toxicity
Azathioprine
Drug that inhibits biotransformation of azathioprine and mercaptopurine, increasing toxicity
Allopurinol
Drug that is converted to mycophenolic acid, inhibits purine (GMP) synthesis
Mycophenolate mofetil
Mycophenolate mofetil is converted to this, which inhibits purine (GMP) synthesis
Mycophenolic acid
Mycophenolate mofetil is converted to mycophenolic acid, which inhibits this
Purine synthesis (suppresses both B and T cell activation)
2 adverse effects of mycophenolate mofetil
Bone marrow suppression
Increased risk of infection
Monoclonal antibodies that bind PD-1 on T cells, preventing interaction with PDL1 on tumor cells
Blocks the anti-proliferation signal that activated PD-1 produces in T cells
Pembrolizumab
Pembrolizumab is monoclonal antibodies that binds this
PD-1 on T cells
Blocks the anti-proliferation signal that activated PD-1 produces in T cells
Lymphokine that stimulates production of T cells and activates natural killer cells
Recombinant interleukin-2 (rIL-2)
rIL-2 has this effect
Stimulates production of T cells and activates NK cells
Fatal multifocal leukoencephalopathy is an adverse effect associated with this
Rituximab
Hypotension that is minimized with pretreatment with corticosteroids is an adverse effect associated with this
Anti-thymocyte globulin
Increased risk of cytomegalovirus infections is an adverse effect associated with this
Anti-thymocyte globulin
Increased risk of infections such as oral candidiasis is an adverse effect associated with this
Glucocorticoids
Adrenal suppression is an adverse effect associated with this
Glucocorticoids
Hyperlipidemia is an adverse effect associated with these
Calcineurin inhibitors, Sirolimus and Everolimus
Nephrotoxicity is an adverse effect associated with this
Tacrolimus
Neurotoxicity is an adverse effect associated with this
Tacrolimus
Renal failure from Sirolimus and Everolimus is more common when combined with this
Cyclosporine
Angioedema is an adverse effect associated with this
Everolimus (also Sirolimus)
Bone marrow suppression is an adverse effect associated with these 3 drugs
Sirolimus/Everolimus, Azathioprine, and Mycophenolate Mofetil
Binds to nuclear receptors to promote T cell death by inhibiting NFkB activation
Glucocorticoids
Drug class that blocks PD-1 signaling to enhance anti-tumor immunity
Immune checkpoint inhibitors
Polyclonal antibodies used to induce immune suppression and terminate transplant rejection
Anti-thymocyte globulin
