Christine Edmead Flashcards
(25 cards)
What are the effects of cytokines?
- induces T and B cell differentiation
- Activation of macrophages
- Cellular migration (chemokines)
- Apoptosis (TNF and FasL)
What cytokines do TH2 cells release?
TH2 releases anti-inflammatory cytokines IL-10, IL-11 and IL-4
Chronic inflammation is largely driven by what cytokines?
TNF and IL-1
What is the first line treatment of RA?
NSAIDS
What is the second line treatment for RA?
DMARDS
generally monotherapy
Why aren’t combination therapies of DMARDs recommended in RA?
Only have a limited no. of options, combinations will use these up quickly
Generally have no synergistic response
What is methotrexate?
Folate antagonist, antiproliferative effect via inhibition of dihydrofolate reductase
What does of methotrexate should be given in RA?
7.5mg-15mg/week
What are the side effects of methotrexate?
Depression of bone marrow and GI tract damage
What are the side effects of penicillamine?
Side effects in 40% of patients. Taste disturbances, rashes, thrombocytopenia, autoimmune disease
What is the general MOA of DMARDs?
Inhibit macrophage activation
Inhibit cell proliferation
Decrease the release of proinflammatory cytokines and ROS
Where are endogenous corticoids released from?
Adrenal cortex
Mineral corticoids affect what?
Water-electrolyte balance
Addisons is caused by what?
Deficiency in glucocorticoid
Cushings syndrome is caused by what?
Excessive glucocorticoid
Conns syndrome is caused by what?
Excessive mineralcorticoid
What is the MOA of glucocorticoids?
Glucocorticoids enter cells and bind to cytoplasmic receptors
This complex translocated to the nucleus to act as a transcription factor
Binds to response elements and activates gene transcription
Can interact and inhibit binding of other transcription factors (AP-1, NFKB)
What are the metabolic side effects of steroids?
Osteoporosis - decrease collagen synthesis, osteoblast functions, Cas absorption
Diabetogenic plus increase in appetite
Mineralcorticoid effects - water retention, hypertension, oedema, and CV events.
What are the two forms of IL-1 and the difference between them?
Il-1 alpha - mainly cystolic or membrane bound
IL-1 beta - most common circulating form
Where is IL-1 synthesised?
Microtubules of monocytes/macrophages
How is IL-1 activated?
IL-1 is synthesised as a precursor in microtubules. CD40L activates ICEC in EC and SM cells. Cleaved by ICE (IL-1 converting enzyme), which is also known as capsases. This release is facilitated by ATP acting on receptor P2X7.
What are the effects of IL-1?
High concentration enters the blood and causes fever
Increased synthesis of COX-2 and iNOS
Increased expression of VCAM and ICAM
Increased bone erosion
Doesn’t induce apoptosis and septic shock
What is the MOA of Enlionamab?
Anti-Icam
Blocks cellular adhesion molecules with an ab so T cells cannot migrate into the tissue
What kind of immunotherapy is infliximab?
Chimeric ab
