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Flashcards in mAb inflammation Deck (28)
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1

what does tumor necrosis factor do

inflammatory mediator
increases tissue damage(apoptosis) and cellular proliferation and aggregation
regulation of immune cells and cytokine release

2

high concentration of TNK in synovial fluids in which conditions

rheumatoid arthritis
psoriatic arthritis
ankylosing spondylitis
psoriasis plaques

3

TNF are

a family of cytokines involved in regulatin gthe immune response

4

role of TNF alpha in RA

proinflammatory cytokine cascade
triggers production of other proinflammatory cytokines
facilitates activation of T lymphocytes by foreign antigens
causes t cell accumulation in tissues and neutrophil accumulation in synovial fluid
stimulates fibroblasts and macrophages to release destructive enzymes
stimulates osteoclastogenesis through enhanced expression of RANKL

5

3 TNF alpha antagonists

adalimumab
infliximab
etanercept

6

adalimumab approved for

RA
crohns
psoriatic arthritis
ankylosing spondylitis

7

humira MOA

recombinant monoclonal antibody that binds to human TNF alpha to prevent binding to receptor
doesnt block TNFbeta

8

drug interactions with humira

kineret
methotrexate
live vaccines

9

infliximib MOA

neutralizes biological activity of both soluble and transmembrane forms of TNFalpha by preventing binding to its receptor but doesnt neutralize TNF beta

10

which is the only antiTNF given IV

infliximab

11

as a chimeric antibody infliximab is expected to have higher rates of

immunogenicity

12

patients with antidrug to antibodies to infliximab are more likely to

have higher rates of drug clearance
reduce efficacy
2x increased incidence of infusion reactions

13

black box warning for infliximab

infection and malignancy risks
contraindication for high dose in heart failure

14

etanercept is a

dimeric soluble dusion protein composed of parts of the ligad binding regions of the p75 high affinity type 2 TNF receptor which binds TNF alpha and TNFbeta linked to parts of the IgG1 Fc regions

15

entanercept MOA

fuses with TNKalpha and beta???? idk

16

abatacept use

RA with inadequate response to DMARDS

17

abatacept is a fusion protein consisting of...

the extracellular domain of CTLA4 and a modified Fc portion of IgG1
doesnt fix complement due to the modification of Fc portion

18

abatacepy MOA

costimulation modulator that binds CD80 and CD86 and blocks their interaction with CD28 inhibiting T cell activation

19

omalizumab is used for

allergic asthma

20

omalizumab binds to

free IgE in the blood and interstitial fluid, membrane bound IgEon the surface ofB lymphocytes
doesnt bind to IgE that is already bound by the high affinity IgE receptor on mast cells and basophils

21

main adverse effect of omalizumab

anaphylaxis

22

natalizumab is a

recombinant humanized IgGK monoclonal antibody
first selective adhesion molcule inhibitor

23

natalizumab is used for

MS

24

what are integrins

heterodimers of noncovalently associated glycoprotiens composed of alpha and beta
cell adhesion receptors involved in interactions between cell extracellular matrix and cell-cell interactions
main way cells bind to and respond to the extracellular matrix

25

expression of what 2 things are increased in MS

VCAM1 immunoglobulin
VLA3 transmembrane alpha4 integrin receptor

26

natalizumab MOA

binds to alpha 4 subunit of alpha4beta1 and alpha4beta7 integrins expressed on the surface of all leukocytes and competitively inhibits alha 4 subunit mediated adhesion of leukocytes to the adhesion molecules

27

how is natalizumab beneficial in MS

inhibits the migration of immune cells into the CNS
inhibits interactions between beta 4 integrins and its ligands

28

what is PML (reported in treatemtns with natalizumab)

opportunistic infection of the brain which leads to death or severe disability
thus why natalizumab is only availble through a restricted distribution program