BL- IMMUNOMODULATOR

Question 1

By________we mean the use of drugs, alone or in combination with other maneuvers, to change the function of all, or part, of the immune system

Answer 1

immunomodulation

Question 2

Immunomodulation Main categories

Answer 2

1. Non-steroidal anti-inflammatory drugs (NSAIDs).
2. Disease-modifying antirheumatic drugs (DMARDs).
3. Glucocorticoids.
4. Biological response modifiers.
5. Tumor-specific monoclonal antibodies.
6. Other antibodies.
7. Miscellaneous drugs

Question 3

The typical monoclonal antibody derives from the progeny of a single B cell, that has been fused with a multiple myeloma tumor cell; the resultant hybrid line can grow forever in culture like its tumor parent, but make the _______of its B cell parent.

Answer 3

specific antibody

~ 33 are already drugs

Question 4

The first monoclonals were made using B cells directly derived from immunized mice; such antibodies are:

Answer 4

murine (mice)- e.g., ibritumomab

Most are made this way

Question 5

Monoclonal Antibodies definition

Answer 5

monospecific antibodies that are made by identical immune cells that are all clones of a unique parent cell, in contrast to polyclonal antibodies which are made from several different immune cells

Question 6

Mouse Multiple Myeloma

Answer 6

These cells make antibodies and live “forever”

Now we can transform these (genetically) to make monoclonal ABs and be immortal

• We deleted its light and heavy chain
• We “fused” m.m.m w/ the cell we wanted creating a hybrid

Question 7

These are all examples of:

Non-steroidal anti-inflammatory drugs (NSAIDs). Disease-modifying antirheumatic drugs (DMARDs). Glucocorticoids. Biological response modifiers.Tumor-specific monoclonal antibodies. Other antibodies.

Answer 7

Immunomodulation Main categories

Question 8

There are monoclonals which are ______-zumab

Answer 8

humanized

Question 9

We deleted its light and heavy chain

We “fused” m.m.m w/ the cell we wanted creating a hybrid

Why do this?

Answer 9

How we use Mouse Mult. Myeloma to make monoclonal ab’s

Question 10

Many of these agents are antibodies to various components of the immune or inflammatory system (which stimulate, inhibit, or opsonize, depending on the designer’s intentions).

Answer 10

BIOLOGICAL RESPONSE MODIFIERS

Question 11

Do you use a B cell mmm hybride that sees self and tumor cell?

Answer 11

No

Question 12

Hybridoma

Answer 12

is a technology of forming hybrid cell lines (called hybridomas) by fusing an antibody-producing B cell with a myeloma (B cell cancer) cell that is selected for its ability to grow in tissue culture and for an absence of antibody chain synthesis.

Question 13

Antibody to_______should be useful, and quite a few monoclonal antibodies (mAb) are already available

Answer 13

tumor-associated antigens

Question 14

Do you use a B cell/mmm hybride that sees tumor cells but not self?

Answer 14

Yes

Question 15

Essential anti-inflammatories in transplantation. Usually start with very high
dose, taper as soon as possible; discontinue if possible. High doses can also be used briefly for threatened rejection episodes.

Answer 15

Glucocorticoids

Question 16

is a technology of forming hybrid cell lines (called hybridomas) by fusing an antibody-producing B cell with a myeloma (B cell cancer) cell that is selected for its ability to grow in tissue culture and for an absence of antibody chain synthesis.

Answer 16

Hybridoma

Question 17

agent decreases DNA synthesis and mRNA

transcription. It is gradually being replaced

Answer 17

Azathioprine (related to 6-mecaptopurine):

Question 18

primary function is to decrease IL-2 production. Thus it is synergistic with
glucocorticoids which, by down-regulating macrophage function as APCs, lessen stimulation of
T cells.

Answer 18

Cyclosporine-A

Question 19

What is the problem with mouse monoclonal antibodies?

Answer 19

We react to the mouse protein
Make AB against it
So its better for one time use
(good for like transplants!)

Question 20

drug is less toxic and has the same mode of action as azathioprine

Answer 20

Mycophenolate mofetil.

Question 21

How can we improve mouse monoclonal antibodies so they can be used more than once?

Answer 21

Only need the variable region of the AB

Replace all else with human protein

Accomplish this with gene inserion into the Hybridoma

Creates Chimeric

*Can be used more than once

Question 22

HACA

Answer 22

Human anti-chimeric antibody. Eventually deveples against Chimeric

Question 23

Humanized monoclonal antibody only maintains ____ from the mouse antibody

Answer 23

CDR

Question 24

Only need the variable regionof the AB

Replace all else with human protein

Accomplish this with gene inserion into the Hybridoma

Creates______

Answer 24

Chimeric

Question 25

HAHA

Answer 25

forms against humanized antibodies

Question 26

Humira

Answer 26

Human antibody against tnf-alpha- Treats arthritis, ankylosing spondylitis, Crohn disease, or similar problems.

Question 27

Humira is made by

Answer 27

Mouse with SCID given human thymus, bone marrow, and lymph mode. B cell against tnf-alpha found and used

Question 28

-umab

Answer 28

Human monoclonal ab

Question 29

-zumab

Answer 29

humanized monoclonal ab

Question 30

Fully human mAb to TNFα. It has been shown to slow the progress of RA, and thus is a BRM and a DMARD, technically. Approvals: RA, JRA, psoriatic arthritis, ankylosing spondylitis, Crohn, ulcerative colitis, psoriasis

Answer 30

Humira

Question 31

-ximab

Answer 31

Chimeric

Question 32

Anti-IL-6 receptor. For use in ____when response to DMARDs is inadequate.

Answer 32

RA

Question 33

Chimeric mAb to CD20. Used to treat non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. For RA when anti-TNF therapy fails, and for Wegener’s granulomatosis. Off-label for MS.

Answer 33

rituximab

Question 34

_______cells are large granular lymphocytes (LGL) which make up 5-10% of blood lymphocytic cells, with mechanisms available similar to those of CTL, but they
do not have rearranged V(D)J genes and are not thymic-derived

Answer 34

NK (natural killer)

Question 35

_______ are a type of cytotoxic lymphocyte critical to the innate immune system. Their role is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response.

Answer 35

Natural killer cells or NK cells

Question 36

NK cells can kill ______ cells, although you have never been exposed

Answer 36

Tumor cells, by virtue of their oddness

Question 37

NK cells have _____ in the cytoplasm

Answer 37

GRANULES

Question 38

NK (natural killer) cells are LARGE granular lymphocytes (LGL) which make up 5-10% of blood lymphocytic cells, with mechanisms available similar to those of CTL, but they
do not have________ genes and are not thymic-derived

Answer 38

rearranged V(D)J

Question 39

NK cells are part of the _____ immune system

Answer 39

innate

Question 40

NK cells have receptors that attract them to

Answer 40

damaged or stressed cells, like tumor cells

NK killing

Question 41

NK has receptors for

Answer 41

the Fc portion of ABs

Antibody-dependent cell-mediated cytotoxicity, or ADCC

Question 42

few NK receptors which recognize molecules on the surface of ‘stressed’ or dysregulated cells, such as virally infected cells or many tumors, which they then kill; therefore, they are part of the:

Answer 42

innate immune system

Question 43

ADCC works because NK cells also have receptors for the Fc end of IgG (FcγR), and so they have an _______way to interact with target cells.

Answer 43

antibody-dependent