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Flashcards in BL- IMMUNOMODULATOR Deck (43):
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

immunomodulation

2

Immunomodulation Main categories

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

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.

specific antibody

~ 33 are already drugs

4

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

murine (mice)- e.g., ibritumomab

Most are made this way

5

Monoclonal Antibodies definition

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

6

Mouse Multiple Myeloma

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

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.

Immunomodulation Main categories

8

There are monoclonals which are ______-zumab

humanized

9

We deleted its light and heavy chain

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

Why do this?

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

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).

BIOLOGICAL RESPONSE MODIFIERS

11

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

No

12

Hybridoma

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.

13

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

tumor-associated antigens

14

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

Yes

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.

Glucocorticoids

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.

Hybridoma

17

agent decreases DNA synthesis and mRNA
transcription. It is gradually being replaced

Azathioprine (related to 6-mecaptopurine):

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.

Cyclosporine-A

19

What is the problem with mouse monoclonal antibodies?

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

20

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

Mycophenolate mofetil.

21

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

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

22

HACA

Human anti-chimeric antibody. Eventually deveples against Chimeric

23

Humanized monoclonal antibody only maintains ____ from the mouse antibody

CDR

24

Only need the variable regionof the AB

Replace all else with human protein

Accomplish this with gene inserion into the Hybridoma

Creates______

Chimeric

25

HAHA

forms against humanized antibodies

26

Humira

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

27

Humira is made by

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

28

-umab

Human monoclonal ab

29

-zumab

humanized monoclonal ab

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

Humira

31

-ximab

Chimeric

32

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

RA

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.

rituximab

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

NK (natural killer)

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.

Natural killer cells or NK cells

36

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

Tumor cells, by virtue of their oddness

37

NK cells have _____ in the cytoplasm

GRANULES

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

rearranged V(D)J

39

NK cells are part of the _____ immune system

innate

40

NK cells have receptors that attract them to

damaged or stressed cells, like tumor cells

NK killing

41

NK has receptors for

the Fc portion of ABs

(Antibody-dependent cell-mediated cytotoxicity, or ADCC)

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:

innate immune system

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.

antibody-dependent