Immune-4 Flashcards

1
Q

what are 2 main drug classes

A

biologics and small molecules

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2
Q

what is the size of small molecules

A

less than 900Da (low MW)

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3
Q

what is the structure of small molecules

A

well defined

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4
Q

what is the target of small molecules

A

well known receptors or enzymes

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5
Q

what are biologics

A

pharmaceutical drug product manufactured in, extracted from, or semi synthesized from biological sources

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6
Q

what are some examples sources of biologics

A

blood, blood products, cells, tissues, organs, xenographs, gene therapies, vaccines, biotechnology

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7
Q

what are xenographs

A

transplantation of living cells, tissues or organs from one species to another

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8
Q

what are 3 examples of targeted therapeutic proteins (recognize the target specifically)

A
  • antibodies
  • antibody fusion proteins
  • antibodies conjugates
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9
Q

what are therapeutic antibodies based on

A

normal functions of immunoglobulins

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10
Q

what are 3 normal functions of immunoglobulins

A
  • circulate in blood and lymphatic system
  • bind to antigens expressed on cells
  • cells bound to antibodies are marked for destruction by macrophages and complement
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11
Q

what are 2 examples of using antibodies therapeutically

A

bind to human antigens (cancer)

neutralize growth factors

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12
Q

which is the fab domain

A

antigen binding fragment, complementariyy determining regions, define antigen specificity

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13
Q

which is the fc domain

A

has binding domains for comlement fixation and binding to cellular Fc receptors

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14
Q

what is in the light chain

A

1 variable region and 1 constant region

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15
Q

what is in the heavy chain

A

1 variable region and 3 constant regions

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16
Q

what is the difference between polyclonal and monoclonal antibodies

A

poly makes it have the affinity for the same antigen but different epitopes, monoclonal is just one epitope

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17
Q

what is an epitope

A

Epitope = the part of an antigen molecule to which an antibody attaches itself

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18
Q

does one antigen have many or one epitope

A

many

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19
Q

what are the 4 types of monoclonal antibodies and the %

A

murine(0%), chimeric(65%), humanized(>90%), fully human(100%)

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20
Q

which monoclonal antibody has the highest potential for immunogenecity

A

murine

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21
Q

which monoclonal antibody has the lowest potential for immunogenecity

A

fully human

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22
Q

which monoclonal antibody is omab

A

murine

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23
Q

which monoclonal antibody is ximab

A

chimeric

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24
Q

which monoclonal antibody is zumab

A

humanized

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25
which monoclonal antibody is umab
fully human
26
what do you call chimeric antibody
ximab
27
what do you call humanized antibody
zumab
28
what do you call fully human antibody
umab
29
what do you call murine antibody
omab
30
what do chimeric monoclonal antibody contain
antigen binding variable regions from immunized animals grafted onto human constant regions
31
what % of each animal in chimeric
33% mouse and 67% human
32
what kind of antibodies do chimeric monoclonal antibody make (but not much of)
human anti mouse antibodies (HAMA)
33
how fast are chimeric monoclonal antibody cleared from the body
more slowly
34
what kinda mechanisms do chimeric monoclonal antibody tend do engage
indirect (idk)
35
what do humanized monoclonal antibody contain
only rodent complementary determining region of the original antibody grafted onto a human antibody framework
36
what is the half life of humanized monoclonal antibody
long
37
do humanized monoclonal antibody have HAMA
minimal
38
do humanized monoclonal antibody maintain antigen recognition qualities
yes
39
do humanized monoclonal antibody or chimeric have more HAMA
chimeric
40
what is the structure of fully human monoclonal antibodies
100% human
41
do fully human monoclonal antibodies activate the immune system
no
42
what are 4 direct actions of mAB based therapy
- ligand blockage - receptor blockage - receptor downregulation - signalling induction
43
what are 3 mechanisms of indirect cell death/ cell depletion of mAB based therapy
- antibody dependent cellular toxicity (ADCC) - complement dependent cytotoxicity (CDC) - complement dependent cellular cytotoxicity (CDCC)
44
what does indirect mAB based therapy cause
depletion, cell death
45
what mediates the indirect mAB based therapy mechanisms
the immune system
46
which is the indirect mechanism that most mAB engage in
antibody dependent cellular toxicity (ADCC)
47
are mAbs able to activate the classical complement pathway and why
no because they are unlikely to reach surface density
48
what happens in antibody dependent cellular toxicity (ADCC)
-antibodies against surface proteins, binds to target, Fc receptors bring on natural killer cells and macrophages to kill the target cell
49
what happens in complement dependent cytotoxicity (CDC)
Antigen recognized by antibody, antibody on surface of target cell, the antibody activates the complement Forms the MAC which lyses the target cells
50
what happens in complement dependent cellular cytotoxicity (CDCC)
Antibody activates complement which activates cells - the immune cells(natural killer cells and macrophages) have receptors which are put there by complement
51
what is a pro to small molecules
more convenient to administer (oral)
52
what is a con to small molecules
extensive plasma concentrations variation among patients
53
what is the main pro to mAbs
they are a lot more specific (facilitates precise action, associated with less toxicity)
54
what is another pro to mAbs besides specificity
they they have longer half lives, so infrequent dosing
55
what are 2 cons to mAbs
- needles | - poor ability to penetrate into tissues and tumors
56
can mAbs cross the BBB
no
57
are human or chimeric more specific
the same
58
what are recombinant fusion proteins
chimeric bi-functional proteins
59
what composes recombinant fusion proteins
- antibody or antibody fragment (Fc) | - functional effector molecule (receptor, ligand)
60
how are all recombinant fusion proteins named
with "cept" at the end
61
what are fused in recombinant fusion proteins
the binding site of receptor to the antibody Fc
62
what do recombinant fusion proteins act as
decoy receptor
63
are recombinant fusion proteins small molecules or biologics
biologics
64
what does it mean that recombinant fusion proteins work as decoy receptors (example)
Give fusion protein with receptor for TNF -Instead of binding to receptor on cell, it will bind to the decoy protein Mostly for blocking
65
what does the Fc region do for recombinant fusion proteins
it improves the proteins half life and other pharmacological properties
66
are recombinant fusion proteins or antibodies more expensive
recombinant fusion proteins