Immune Manipulation Flashcards
Differentiate immunosuppression (6) and immunopotentiation (4)
Immunosuppressants: NSAIDs, Glucocorticoids, Calcineurin inhibitors, Antiproliferative agents, Cytotoxic agents, Antibodies
Immunopotentiators: Interleukins/Interferons, Immunizations (active and passive), Colony-Stimulating factors
Recall the pro-inflammatory cytokines (6) and predict the effect of blocking TNF-alpha production or its action
- Pro-inflammatory Cytokines: IL-1, TNF-alpha, TNF-beta, IFN-gamma, IL-6, IL-8 (MAJOR ones are TNF-alpha and IL-6)
- TNF-alpha sources: Macrphages, TH1 cells, Cytotoxic T cells
- TNF-alpha actions: T and B cell activation, pyrogenic, cytotoxicity
- TNF-inhibitor will shut off inflammation
Identify the site of action for NSAID’s in the arachidonic acid pathway?
NSAID’s block the COX pathway
Differentiate polyclonal and monoclonal antibodies
Monoclonal: Antibodies derived from a single B-cell against a single epitope on a single antigen. Very pure and specific
Polyclonal: Antibodies derived from multiple B-cells against multiple epitopes on a single antigen. Used to treat primary antibody deficiencies and some immune-related conditions like ITP (blockade of IgG receptors)
What is the difference between chimeric and humanized monoclonal antibodies?
Chimeric: 33% mouse, 66% human
- Mouse portion is the region that binds the antigen (Fab)
- Human portion if heavy chain region (Fc)
Humanized: 5% mouse, 95% human
- Very tip of Fab region is mouse (exquisite specificity)
Given the generic name of a therapeutic monoclonal antibody, identify the source of a monoclonal antibody and its general target
Nomenclature: Target--Source--"mab" Targets: - Ci(r) = circulatory - Li(m) = immune - tu(m) = tumor Sources: - umab = human - ximab = chimera - zumab = humanized
Identify the site of action for corticosteroids in the arachidonic acid pathway?
What condition is this especially helpful with?
Corticosteroids block Phospholipase A2 - this prevents 5-Lipoxygenase (LOX) pathway from causing bronchospasm, vasoconstriction, and increased permeability.
Especially important in Asthma.
What prostaglandin does low dose NSAID (aspirin) irreversibly bind to and therefore block in the arachidonic acid cascade? What is this PG responsible for?
Which prostaglandin does it bind to, but the cell can still produce more? What is this PG responsible for?
Irreversibly binds to and blocks: Thromboxane A2 (TXA2) - responsible for inflammation (COX-2)
LOW dose aspirin binds to, but the cell can produce more: Prostaglandin I2 (PGI2) - responsible for protecting stomach (COX-1)
Aspirin is known for being harsh on your stomach. Why is this?
Aspirin itself does not hurt the stomach because of acidity in the drug.
Aspirin can be harsh on the stomach because it blocks the COX pathway and in high doses it blocks both TXA2 (therefore reducing inflammation) and it blocks PGI2 (therefore reducing the stomach’s “protection”)
What are the two types of Cyclooxygenase?
COX-1: expressed in most cells; predominantly in gastric mucosa and kidneys; Prostaglandin I2 (PGI2)
COX-2: Inducible/not expressed under normal conditions; increased during inflammation; Thromboxane A2 (TXA2)
At low dose, what does aspirin specifically bind to/block?
COX-2…Thromboxane A2 (TXA2)
What is Abciximab used for?
Anti platelet drug
What is Bevacizumab used for?
Angiogenesis inhibitor
What is Adalimumab used for?
TNF-inhibitor
What is Rituximab used for?
Lymphoma drug
