Immunpharmacology Flashcards
Time for development of primary immune response…
Activation of T cells and AB production takes…
8-14d
1-3d
Basophils release…
- histamine
- bradykinin
- serotonin
- heparin
- SRSA
Immunosuppressants generally work better for______
primary immune response
Acute rejection is mainly mediated by ____ and ___
T cells and cytokines
Three routes of immunosuppression
- Decrease amount of lymphocyte
- Divert lymphocyte traffic
- Block pathways involved in lymphocytic response
6 catergories of immunosuppressants
- regulators of gene expression
- alkylating agents
- inhibitors of de novo pyrimidine synth
- inhibitors of de novo purine synth
- Kinase + phosphatase inhibitors
- Protein immunosuppressive drugs
Adrenocortical steroid MOA (3)
- reduce levels of lymphocytes
- Block antigen presentation pathway
- Inhibit IL-2 gene transcription whih is needed for B and T cell clonal expansion
Example of alkylating agent
cyclophosphamide (cytotoxic)
Examples of first and second generation inhibitors of de novo purine synthesis
1st gen = AZT + 6-Mercaptopurine
2nd Gen = mizoribine + mycophenolate mofetil
What is MMF
inosine 5-MP dehydrogenase inhibitor
Methotrexate and polygentamate derivatives also belong to which class of drugs?
Purine synthesis inhibitors
Alkylating agents and Purine synthesis inhibitors – how to they induce/maintain immunosuppression
Block DNA/RNA synth
Prevent clonal expansion of B/T cells
Examples of Pyrimidine inhibitors
What is the MOA?
- Brequinar
- Leflunomide
- malononitrilomides
inhibit dihydroorotate dehydrogenase
Kinase and phosphatase inhibitor drugs
Cyclosporine and tacrolimus
Cyclosporine concentrates in _____
It is given ___ prior to ____
**MOA?**
Red/white cells
give 4-24h before transplant
Inhibits the phosphatase activity of calcineurin
= prevents NFAT translocation
**also blocks JNK and p38 signaling
Tacrolimus category and MOA
macrolide
binds to FK506-BP 12
= inhibits the phosphatase activity of calcineurin
Sirolimus MOA
What is unique?
Binds FKBP12
(same as tacrolimus)
Complex formation with FKBP12 does not inhibit IL-2 production
Antilymphocyte globulins (protein immunosuppressives)
muromonab-CD3
Daclizumab
Basiliximab
AntiCD25 mAb’s
Daclizumab and Basiliximab
Anti CD3 mAb that binds to TCR-associated CD3 complex and alters T cells
Muromonab
RA and Hemolyitc Anemia are diseases that involves overexpression of _____
They would benefit from _____
CD20
Anti CD20 mAb’s (which are difficult to make beacuse of CD20’s short extramembrane domain)
Belatacept is a _________
Its MOA?
“co-stimulatory blocker”
Inhibits CD28-mediated costimulation by binding to CD80 and CD86 –> blocking engagement of CD28 on T cells
Use of beletacept is associated with
serious side effects in children
Selective targeting of ___ rather than ___ may be more effetive to control post-transplant immune responses
CD28 rather than CD80/86
Rapamycin is a _____ that targets _____
macrocyclic lactone
mTOR (regulator of proliferation)
Rapamycin is generally replaced by ____
everolimus
Everolimus is being tried in patients with ______
renal insufficiency or neoplasia
Fingolimod is structurally related to ____
Function?
Myricin (sphingosine analog)
Drives lymphocytes into lymphoid tissue (reducing the number of circulating T cells)
TNFa inhibitor
Used for?
certolizumab pegol
RA
Three antibody mediated diseases
AI-mediated Hemolytic Anemia
M.Gravis
Hypoadrenocorticism
Two immune complex diseases
SLE
RA
Antibody/T cell mediated diseases
Thyroiditis
AI hypothyroidism
AI diseases also arise from deficiencies of
Complement enzymes
AZT is metabolized to give ___
mercaptopurine
mercaptopurine is mainly focused on…
humoral immunity
Leflunomide is a ____ that is used to treat ____
prodrug of pyrimidine inhibitor
RA
Cyclosporine – important fact in treatment
diet must remain consistent without any deviations, blood levels must be closely monitored
Systemic allergy treatment now includes
Fatty acids (linoleic and gamma linolenic)
H1 blockers (common)
Newer gen blockes
Common = diphenhydramine, promethazine, chlorpheniramine
New = Rupatadine, cetirizine, fexofenadine
In patients with extensive immunnosuppressive therapy, it is important to treat with
prophylactic antivirals
Possible approach fo GvsHD
Adenosine agonists (targeting A2A receptors)
Most immunostimulants have _______
nonspecific activity toward immune system
Echinacea MOA
stimulation of phagocytosis
production of interferon and TNF
Acemannan MOA
induces MQ activity and IL-1 production
Beta1,3 Glucan MOA (3 effects)
binds B1,3Glucan receptor on MQ
- Causes nonspecific phagocytosis
- Causes release of IL1 and IL2 (trigers other cell lines like T cells)
- Stimulates bone marrow production
Beta1,3 glucan for what diseases
retroviral, tumors, chemo/radiation
QS21 MOA
amplifies B and T cell mediated responses
Detoxified Freunds Adjuvant is composed of ______ and causes ________
monophosphoyl lipid A
induces T cells to secrete IFNg
Immunoglobulin therapy results in
prevention of virus penetration into cells
for THREE months
IVIG used for (6)
- Hep A
- Parvo
- Enterovirus
- Zoster
- Hep B
- RSV
Cytokines
IL-2 and IFNa