1. histamine 2. bradykinin 3. serotonin 4. heparin 5. SRSA

Immunpharmacology Flashcards by Chris Rodarte

Time for development of primary immune response…

Activation of T cells and AB production takes…

8-14d

1-3d

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Basophils release…

histamine
bradykinin
serotonin
heparin
SRSA

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Immunosuppressants generally work better for______

primary immune response

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Acute rejection is mainly mediated by ____ and ___

T cells and cytokines

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Three routes of immunosuppression

Decrease amount of lymphocyte
Divert lymphocyte traffic
Block pathways involved in lymphocytic response

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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

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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

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Example of alkylating agent

cyclophosphamide (cytotoxic)

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Examples of first and second generation inhibitors of de novo purine synthesis

1st gen = AZT + 6-Mercaptopurine

2nd Gen = mizoribine + mycophenolate mofetil

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What is MMF

inosine 5-MP dehydrogenase inhibitor

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Methotrexate and polygentamate derivatives also belong to which class of drugs?

Purine synthesis inhibitors

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Alkylating agents and Purine synthesis inhibitors – how to they induce/maintain immunosuppression

Block DNA/RNA synth

Prevent clonal expansion of B/T cells

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Examples of Pyrimidine inhibitors

What is the MOA?

Brequinar
Leflunomide
malononitrilomides

inhibit dihydroorotate dehydrogenase

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Kinase and phosphatase inhibitor drugs

Cyclosporine and tacrolimus

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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

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Tacrolimus category and MOA

macrolide

binds to FK506-BP 12

= inhibits the phosphatase activity of calcineurin

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Sirolimus MOA

What is unique?

Binds FKBP12

(same as tacrolimus)

Complex formation with FKBP12 does not inhibit IL-2 production

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Antilymphocyte globulins (protein immunosuppressives)

muromonab-CD3

Daclizumab

Basiliximab

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AntiCD25 mAb’s

Daclizumab and Basiliximab

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Anti CD3 mAb that binds to TCR-associated CD3 complex and alters T cells

Muromonab

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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)

1. Hep A 2. Parvo 3. Enterovirus 4. Zoster 5. Hep B 6. RSV

Cytokines

IL-2 and IFNa