adaptive immune response is directed by? (2)
-cytokines from T helpers
-antibodies from B cells
How do administered antibodies depress the immune system? (2)
-opsonize & deplete T cells
-neutralize antigens before they can elicit an immune response (Rh negative mothers)
What are the 3 key steps in T activation? (will be drug targets)
-engagement TCR & co-receptors
-expressions of cytokines
On top of the 3 key steps in T activation (see previous card), what is the 1 additional way immune suppression is achieved in T helpers?
-TCR signal transduction is targeted
For visual people, here's a picture of those 4 ways.
What are the 2 kinds of useful immune stimulants?
-cytokines: IL-2, IFN-alpha & gamma!!
-environmental agents that up antigen presentation (BCG, alum)
Activated T cells secrete what cytokine & express what receptor?
-CD25 (IL-2 Receptor)
What does IL-2 do?
stimulates clonal expansion of antigen-specific T cells
Which immune cells do T cell secreted cytokines influence?
Th1 response secretes _____ cytokine which increases _____ function against _____ type of pathogen
Th2 response secretes ______ cytokine which initiates ______ action against ______ pathogen
-humoral (mostly IgE)
-multicellular parasites (and allergies)
Th17 response secretes ______ cytokine with function _____ against _______ type of pathogen
-extracellular bacteria & fungi, also autoimmune
What is the main problem with immunostimulants?
cascade effect increases release of cytokines/inflammation mediators downstream
What symptoms do downstream cytokines cause?
flu-like (fever, chills)
When are times you'd use an immune stimulator? (review, don't memorize)
enhance vaccination response
What are the 2 adjuvants?
BCG (bacillus calmette-guerin)
______ is most common adjuvant in human vaccines?
How does alum work?
forms deposits w/ antigens and prolongs exposure to them, may increase APC activity.
which adjuvant has few side effects?
What is the main use of BCG?
How does BCG work? (2)
-puts antigens in contact w/ pattern recognition receptors
-direct activation of leukocytes (so strong it causes septic shock so only used topically!)
What is IL-2 immune stimulant used for? (2)
-Renal cell carcinoma
What effects does IL-2 have? (4)
-proliferation T cells
-CD 8 activation
-capillary leak ->hypotensive shock
IFN-gamma immune stimulant is used for?
severe recurrent infections
IFN-alpha immune stimulant is used for? (2)
-chronic viral infection
-Reduces frequency of episodes in multiple sclerosis (immune modulatory)
What are the 2 key side effects of all immune suppressants?
What 5 drugs are general inhibitors of clonal expansion?
Which clonal expansion inhibitors are like each other?
-Azathioprine and mycophenolate (for side effects)
-Methotrexate and leflunomide (for uses)
What is the difference in dosage for immunosuppression or anti-neoplasm drugs?
-lower doses for immunosuppression
Xanthine oxidase inactivates which immunosuppressant?
Picture what's going on with calcineurin, NFAT, glucocorticoids, and resulting cytokines.
When NFAT is active, is it 1) phosphorylated? 2)Creating or stopping inflammation?
T/F cyclosporine can be found endogenously, & binds the drug cyclophilin?
F. Cyclophilin is endogenous, cyclosprorine is drug.
Which drug antagonizes tacrolimus? Which drug synergizes with cyclosprine?
What is function of calcineurin?
What is function of NF-AT?
go into nucleus to cause transcription cytokines
IL-2 receptor binding leads to activation of what? which then causes?
-cell growth & proliferation
What is FKBP12?
endogenous, it binds tacrolimus & stops activation of NF-AT by calcineurin.
[Same way cyclophilin bound to cyclosporine acts!]
How are debilitating side effects like nephrotoxicity avoided when using immune suppressants?
They are used in low doses in combination with other immune suppressors
Which 2 immune suppressant drugs combine with the same target? What is that target?
tacrolimus and sirolimus
[Note that tacrolimus does this to stop calcineurin activity, while sirolimus does this to stop mTOR activity!]
What receptor is acted on by over 60 cytokines? What is the function of this receptor? (3)
-Adaptive Immunity, Inflammation, many functions req'd for life!
T/F Jak/stat inhibits ALL activity of cytokines required for adaptive immunity?
Administered Antibodies can be used as therapy in what ways (besides immune suppression, see card at beginning for that info)
-Give passive immunity
-Destroy cancer (herceptin for breast cancer)
Which portion of a chimeric antibody is human?
the Fc region (constant)
Why can't animal Ab's be used long-term in humans?
-Humans mount response against them ->allergic rxn & serum sickness
How are Ab's used to treat Rh neg. mothers? What happens if they aren't used?
-They bind and neutralize the baby's Rh(D) antigens introduced to mom's blood at time of birth.
-Future babies get hemolytic disease
How are Anti-T cell antibodies made?
T cells are injected into animals and then serum IgG is purified from them