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Molecules to Malady > Compounds to Remember > Flashcards

Compounds to Remember Flashcards

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Organic Chemistry 101 flashcards
1
Q

RAG1/2

A

recognizes RSS sequence and cleaves it (as a complex with HMG1)

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2
Q

HMG1

A

chromatin-binding protein (binds with RAG1/2) - required for rearrangement

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3
Q

Artemis

A

A nuclease that cleaves the hairpin structure of the coding joint (as a complex with Ku70,80/DNA-PKcs)

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4
Q

Ig alpha/beta

A

scaffolding protein for pre-BCR and BCR - required for successful signalling of rearrangement into the cell

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5
Q

TdT

A

unique to B cells; non-template, random addition of nucleotides to the end of the coding joint

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6
Q

ADA

A

an enzyme responsible for differentiation in early precursors of lymphovytes; deficiency leads to ADA-SCID (T- B- NK-)

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7
Q

BLNK

A

an adaptor protein; required for successful signalling of rearrangement into the cell

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8
Q

Syk and Btk

A

kinases; required for successful signalling of rearrangement into the cell

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9
Q

TRECS/KRECS

A

biproduct of succesful VDJ rearrangement in T/B cells

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10
Q

IVIg

A

purified IgG from pooled human sera (>1000 donors) using alcohol fractionation; dose is 400-600mg/kg per month in clinic; 2-4 hours per infusion

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11
Q

SCIg

A

Self-administered weekly subcutaneously via small pump; avoid peak/throughs of IVIg

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12
Q

CXCR5

A

chemokine receptor expressed by T cells that is upregulated after encountering antigen in lymphoid organ

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13
Q

CCR7

A

chemokine receptor expressed by B cells that is upregulated after encountering antigen in lymphoid organ

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14
Q

AID enzyme

A
  • introduces nicks into the S DNA region of teh constant region of Ig gene (converting C to U bases) - creating double-stranded breaks
  • introduces point mutations into V genes of GC B cells; important for somatic hypermutation
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15
Q

gp120

A

viral prtoein expressed by HIV that binds to CD4 in T cells to mediate viral entry; gp120/CD4 complex binds to CCR5/CXCR4 on host cell

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16
Q

Collagen/fibronectin

A

produced by Type A synoviocytes; contribute to structural framework of synovial interstitium and cell adherence

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17
Q

Hyaluronan

A

produced by Type A synoviocytes; high MW polysaccharide that maintains synovial fluid viscosity; procides shock absorption

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18
Q

Lubricin

A

mucin-like proteoglycan; protects cartilage surfaces from deposition and cell adhesion; inhibits synovial cell overgrowth

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19
Q

MMPs

A

matrix-metalloproteinases; degrades cartilage; produced by type B synoviocytes

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20
Q

IL-17

A

pro-inflammatory cytokine expressed by TH17 cells, induces expression of other pro-inflammatory cytokines and RANKL in other cells

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21
Q

TNF-alpha

A

expressed by activated macrophages, type B synoviocytes, and T cells; induces pro-inflammatory cytokine release, endothelial cell, osteoclast, and chondrocyte activation; angiogenesis

Increases number of osteoclast progenitors and increase expression of RANK and RANKL

Increase expression of DKK, decrease RUNX2 protein levels, alkaline phosphatase and osteocalcin

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22
Q

IL-1beta

A

inducible form of IL-1; highly pyrogenic and pro-inflammatory; activates leukocytes, endotthelial cells, synovial fibroblasts; induces expression of chemokines, sytokines; induces MMP production by chondrocytes, induces RANKL

produced by type B synoviovytes, macrophages, and endothelail cells, neutrophils

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23
Q

IL-6

A

pro-inflammatory cytokine, involved in fever and acute phase response; induce Ig production in B cells, induce differentiation of TH17 cells and osteoclast (RANKL induction), induce cytokine production

produces by macrophages, type B synoviocytes, and T cells

24
Q

STAT3

A

phosphorylation by JAK receptors - leads to promotion of cytokine expression, supresses type B synoviocytes apoptosis; promote T cell survival, promote antibody production; promotes RANKL expression

25
Q

RF

A

Rheumatoid factor; high-affinity autoantibody against Fc portion of IgG; prior to RA onset, an increase in IgM/IgA

26
Q

DRB1 gene

A

encodes for HLA-DR antigen presenting molecule, allelic variants DRB1*0401/0404 most associated with RA

27
Q

PADI

A

peptidyl-arginine deiminase; respondible for post-translational conversion of the amino acid arginine to citrulline (citrullination); PADI2/4 abundant in RA

28
Q

ACPA

A

antibodies against citrullinated ‘self-proteins’; detected via anti-CCP assay; prior to RA onset, increase in SE spreasing and isotype changes

29
Q

Hydroxypatite

A

Indoluble salt of calcium and phosphorus

30
Q

RANKL

A

member of TNF family ligand - mostly membrane-bound but can be cleaved to a soluble form

induce osteoclast differentiation and activation; produced normally by osteoblasts and osteocytes

produced in RA mostly by type B fibroblasts, osteoblasts, T cells

31
Q

RANK

A

receptor for RANKLS, expressed on osteoclasts and its precursors

32
Q

Osteoprotegerin

A

member TNF-receptor family, binds RANKL (acts as decoy receptor); blocls RANKL-induces osteoclast differentiation and activation

Normally, produced by osteoblasts

33
Q
A
34
Q

IL-1

A

pro-inflammatory cytokine; promotes cell fusion of the mononuclear precursor cells and survival of mature osteoclast

35
Q

Alkaline phosphatase

A

renders osteoid competent for mineral deposition

36
Q

DKK

A

Wnt signalling antagonist; inhibition of Wnt signalling leading to inhibtion of osteoblast amturation and bone formation; expression increase by TNF

37
Q

Methotrexate

A

a csDMARD, anti-metabolite, weekly oral dose; anchor drug, inital DMARD choice in majority of patient

Adverse effect: hepatotoxicity, myelotoxicity

38
Q

Sulfasalazine

A

a csDMARD, anti-inflammatory and anti-microbial; twice daily oral dose

Side effect: hepatotoxicity, myelotoxicity

39
Q

Hydroxycloroquine

A

a csDMARD; daily oral dose - side effect: retinopathy

40
Q

Leflunomide

A

csDMARD, anti-metabolite; daily oral dose; side effects: hepatotoxicity, myelotoxicity, and hypertension

41
Q

Adalimumab

A

Hman monoclonal antibody (IgG1); TNF inhibitor

Side effect: injection site reations, infections

42
Q

Infliximab

A

chimeric antibody, huan IgG1 constant region and mouse vairbale region, anti-TNF

Side effect: injection site reations, infections

43
Q

Etanercept

A

fusion protein: two p75 TNF-alpha receptors and human IgG1 constant region

44
Q

Certolizumab pegol

A

humanised monoclonal antibody (anti-TNF), bound to polyethylene glycol (PEG)

Not inferior to ADA (when combined with MTX) in MTX-IR

Side effect: injection site reations, infections

45
Q

Golimumab

A

human IgG1 monoclonal antibody against TNF

Side effect: injection site reations, infections

46
Q

Abatacept

A

T-cell costimulation blocker; formed by CTLA4 molule dimerized on an Ig frame

non-inferior to ADA (ADA has more injection site reactions) in MTX-IR, b-DMARD naiive

Side effect: injection site reations, infections

47
Q

Anankira

A

IL-1R antagonist

Side effect: injection site reations, infections

48
Q

Rituximab

A

Chimeric monoclonal antibody (anti-CD20) leads to B cel depletion; doesn’t target B cells before Pre-B cell or after Memory B cell in the differentiation phases

non-inferior to ADA/ETA (more cost saving) in sero+ve, naiive RA patients

Side effect: injection site reations, infections

49
Q

Tocilizumab

A

Humaized monoclonal antibody against IL-6R

Superior to ADA (but associated with more AE) in MTX-IR

Side effect: injection site reations, infections, elevated LDL, cytopenias(decrease in platelets and neutrophils)

50
Q

Sarilumab

A

human IgG1 monoclonal antibody against IL-6R (soluble and membrane-bound)

Monotherapy was superior to ADA

Side effect: injection site reations, infections, neutropenia

51
Q

JAK1/2

A

role in growth, neurodevelopment, haematopoesis, host defense

52
Q

JAK3 and Tyk2

A

engaged in immune responses

53
Q

Tofacitinib

A

oral JAK inhibitor; preferentially inhibit JAK1/3

limiting T cel and other leukocyte recruitment - decrease in synovial inflammation and structural damage

adverse effect: headaches, infection, elevated LDL. neutropenia

54
Q

Baricitinib

A

Reversible inhibitor of JAK1/2

Side effects: neutropenia, increase in creatinine and LDL, infection risk, malignancy risk?

55
Q

Upadacitinib

A

Selective inhibitor of JAK1

Adverse reactions: infection, headache, pulmonary embolism

Molecules to Malady (17 decks)

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