BL- IMMUNOMODULATOR Flashcards
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
Immunomodulation Main categories
- Non-steroidal anti-inflammatory drugs (NSAIDs).
- Disease-modifying antirheumatic drugs (DMARDs).
- Glucocorticoids.
- Biological response modifiers.
- Tumor-specific monoclonal antibodies.
- Other antibodies.
- Miscellaneous drugs
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
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
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
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
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
There are monoclonals which are ______-zumab
humanized
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
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
Do you use a B cell mmm hybride that sees self and tumor cell?
No
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.
Antibody to_______should be useful, and quite a few monoclonal antibodies (mAb) are already available
tumor-associated antigens
Do you use a B cell/mmm hybride that sees tumor cells but not self?
Yes
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
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
agent decreases DNA synthesis and mRNA
transcription. It is gradually being replaced
Azathioprine (related to 6-mecaptopurine):
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
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!)
drug is less toxic and has the same mode of action as azathioprine
Mycophenolate mofetil.
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
HACA
Human anti-chimeric antibody. Eventually deveples against Chimeric
Humanized monoclonal antibody only maintains ____ from the mouse antibody
CDR
Only need the variable regionof the AB
Replace all else with human protein
Accomplish this with gene inserion into the Hybridoma
Creates______
Chimeric
HAHA
forms against humanized antibodies
Humira
Human antibody against tnf-alpha- Treats arthritis, ankylosing spondylitis, Crohn disease, or similar problems.
Humira is made by
Mouse with SCID given human thymus, bone marrow, and lymph mode. B cell against tnf-alpha found and used
-umab
Human monoclonal ab
-zumab
humanized monoclonal ab
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
-ximab
Chimeric
Anti-IL-6 receptor. For use in ____when response to DMARDs is inadequate.
RA
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
_______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)
_______ 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
NK cells can kill ______ cells, although you have never been exposed
Tumor cells, by virtue of their oddness
NK cells have _____ in the cytoplasm
GRANULES
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
NK cells are part of the _____ immune system
innate
NK cells have receptors that attract them to
damaged or stressed cells, like tumor cells
NK killing
NK has receptors for
the Fc portion of ABs
Antibody-dependent cell-mediated cytotoxicity, or ADCC
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
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
