Feb 25 2014, Imm Mods, Coagulation, Rheum Flashcards
What is a hybridoma?
A B-cell crossed with a myeloma cell
What are hybridomas good for?
Creating mAb’s for a particular disease
What is HAMA? HACA? HAHA?
Human-Anti-Mouse-Antibody
Human-Anti-Chimeric-Antibody
Human-Anti-Humanized-Antibody
What domains does a chimeric Ab have?
Human constant/variable regions and 1 mouse vL and vH domains
What domains does humanized Ab have?
All human domains, but mouse-derived epitopes
What are the most powerful pro-inflammatory cytokines?
TNFα and IL-1α,β
Why are NK cells really cool in terms of fighting tumors?
NK cells don’t need antigenic stimulation to kill tumor cells! (can grab Fc region on a self-cell)
What is ADCC?
Antibody-Dependent Cell-mediated Cytotoxicity
Why do we care about CTLA-4 and PD-1?
They downregulate CTR’s so tumor cells won’t kill themselves. D’oh!
What is BiTE? What does it do?
Bi-specific T-cell Engager - it forms a link between T cells and tumor cells so T-cells can secrete cytokines into induce cancer cell apoptosis
What is CAR? What does it do?
Chimeric Antigen Receptors - a sophisticated BiTE mAb on steroids
Another name for factor II (two)?
Prothrombin
Another name for factor I?
Fibrinogen
What are the zymogens?
Factors II, VII, IX, X, XI, XII, XIII
What are the vit K dependent factors?
Factors II, VII, IX, X, PC, PS
What is the tenase complex?
Factor VII, Ca2+, and TF (extrinsic) or factors VIII and IX, activated by the negitive phospholipid surface (intrinsic)
What does VWF do?
Binds to Factor VIII so it won’t degrade, also promotes forming the PLT-collagen clot
What’s in the extrinsic pathway?
TF, Factor VII
What’s in the intrinsic pathway?
XII, XI, IX, VIII
What’s in the common pathway?
V, X, II (prothrombin), I (fibrinogen), XIII
Physiologic anticoagulants?
PC, PS, AT3, TFPI, tPA, plasmin
Hemophilia A is a deficiency in which factor?
Factor VIII
Hemophilia B is a deficiency in which factor?
Factor IX
PTT can be equated to which pathway?
Intrinsic
PT can be equated to which pathway?
Extrinsic
What is the key protein in the fibrinolytic pathway?
Thrombomodulin (amps up PC, but disallows for fibrinolysis)
What molecule does Heparin bind?
AT3 (increases anticoagulation)
What molecule does Warfarin bind?
Vit-K oxyreductase (inhibits vit K recycling; is an anticoagulant)
4 Stages of Gout?
1) Asymptomatic hyperuricemia
2) Acute Gouty Arthritis
3) Intercritical Gout
4) Chronic Tophaceous Gout
What crystal is deposited in gout?
MSU, monosodium urate
Who usually is Dx’d with gout?
Men over 30 y/o, females too - only after menopause
What do MSU crystals look like?
Needle-shaped and negatively bifringent (yellow when parallel)
What synovial fluid classification accompanies gout?
Inflamed (WBC > 2,000)
If the Pt has a 24h excretion of uric acid > 750 mg they are an:
Overproducer of uric acid
If the Pt has a 24h excretion of uric acid < 750 mg they are an:
Underexcretor of uric acid
Are most gout patients are overproducers or underexcretors?
Underexcretors
What exchanger in the proximal tubule is responsible for pre-secretory/post-secretory reabsorption of uric acid?
URAT1, urate/organic anion exchanger
Examples of excreted, unwanted organic acids?
Lactate, Acetoacetate, Hydroxybutyrate, Succinate
Activators of URAT1?
nicotinate, pyrazinoate, diuretics, low-dose aspirin
decrease renal excretion of uric acid
Inhibitors of URAT1?
probenecid, sulfinpyrazone, losartan metabolite, high-dose aspirin
(increase renal excretion of uric acid)
Other urate transporters?
OAT4, OAT10, GLUT9a, ABCG2
Which TLRs are associated with gout?
TLR 2, 4
MSU crystals engage _____ which activates _____ which results in IL-1β production
caspase-1 ; NLRP3 inflammasome
Acute gouty attack is treated with_____, ______, and ____
NSAIDs, colchicine (if no renal insufficiency), and corticosteroids
Chronic gouty attack is treated with_____ or _______
a uricosuric or a xanthine oxidase inhibitor
What HLA for gouty Koreans, Han Chinese, or Thai persons?
HLAB*5801
What is CPPD? Cyrstal shape, refraction?
Calcium pyrophosphate dihydrate, rhomboid-shaped, positively bifringent (blue when parallel)
What causes pseudo gout?
CPPD crystals into the joint space - inflammatory!
“Crystal shedding” release into synovium
The difference between pseudogout and gout pathophysiology? Crystals?
Pseudogout: blue CPPD rhomboid crystals, “shed” into joint space
Gout: Yellow MSU needle crystals, precipitate in joint space
RA disease definition?
Systemic, Inflammatory, Auto-Immune disorder resulting in peripheral, symmetric, synovitis
RA vs OA joint symmetry presentation?
RA is symmetric, OA is asymmetric
Some lab values associated with RA?
RF, ESR, CRP (all elevated)
Sx of RA?
Morning stiffness, tissue swelling, pain, tenderness, rubor, calor
What lab value is specific to RA?
CCP, Anti-cyclic citrullinated peptide
Radiographic RA findings?
Osteopenia, symmetric loss of joint space, erosions in marginal distribution
Type of cells in early RA synovial fluid findings?
Mononuclear cells (LY, MO, MØ)
What is pannus?
Organized mass of granulation tissue in the RA joint w/ MØ’s, Tcells, Bcells, and plasma cells
Type of cells in late RA synovial fluid findings?
PMN’s and pannus
Caucasian RA HLA?
HLA-DRB1*0401, *0404. *0101
Asian RA HLA?
HLA-DRB1*0405
Indian RA HLA?
HLA-DRB1*1402
Genes associated with RA?
PTPN22, STAT4, TRAF1-C5
Which cytokines are really important with RA?
IL-1, TNFα, IL-17 (local)
IL-6 (systemic)
What two compartments should we think of with RA?
Synovial fluid compartment (all the bad cytokines)
Synovial tissue compartment (pannus!)
Hemophilia C is a deficiency in which factor?
Factor XI
