Flashcards in Immunomodulators (complete) Deck (19):
What are monoclonal Abs? Describe how they are made.
- Essentially Abs that are made in a lab, but used in a human's immune system
- Progeny of a single B cell => then fused w/ a multiple myeloma tumor cell => hybrid
- Hybrid grows forever in culture (like tumor cell), but produces the specific Ab of the B cell
Why does the single B cell of the monoclonal Ab need to fuse with a tumor cell?
Otherwise the B cell would die quickly in culture
Need the opposite property => fusion w/ tumor cell (has that needed property)
Discuss the use of monoclonal Abs as anti-inflammatory agents
Some tx are monoAbs to inflammation factors like TNF-alpha
IVIG can bind inhibitory Fc receptors on inflammatory cells
Infliximab: used in Crohn, UC, RA, ankylosing spondylitis
Adalimumab (Humira): used in RA, JRA, UC, Crohn, ankylosing spond, psoriasis
What is a murine monoclonal Ab?
A mouse only monoAb
What is a chimeric monoclonal Ab?
- Mouse VL/VH domains, human C domains
- Engineered at the DNA level
What is a humanized monoclonal Ab?
- only mouse CDRs on V domain
- Engineered at the DNA level
What is a human monoclonal Ab?
- To make this you need to "rent" a mouse w/ SCID => add human thymus, lymph node, and BM
- Ex: Humira
What are the disadvantages of murine monoclonal Abs?
Human anti-mouse antibody (HAMA)
- Will result from second exposure to the monoAb
- If it doesn't work the first time, don't give it a second time
What are the disadvantages of chimeric monoclonal Abs?
- Will result after too many exposures to this monoAb
What are the disadvantages of humanized monoclonal Abs?
- This eventually will happen after prolonged exposure to this monoAb
What are the disadvantages of human monoclonal Abs?
- Dr. Cohen's heard of people developing immunity against this, but not likely
- Need to have a super long exposure to do this, theoretically
What are NK cells?
- Large granular lymphocytes (LGL)
- Make up 5-10% of blood lymphocytic cells
- Have mechanisms similar to CTL
- However! they do not have rearranged V(D)J genes and not-thymic derived!
What is ADCC?
Ab-dependent cell-mediated cytotoxicity
- Not all tumor cells express markers that NK cells recognize via NK receptors
- Ab against tumor is added w/ NK cells
- NK cells have receptors for Fc end of IgG
- This is an Ab dependent way to interact with target cells
Describe the effect of Class I MHC expression levels on susceptibility of target cells to CTL cells
CTLs can only target cells with Class I MHC expression
Describe the effect of Class I MHC expression levels on susceptibility of target cells to NK cells
- NK cells can target these and also others
- They do not require the presence of this MHC to kill!
- However, they are downregulated in the presence of MHC Class I b/c technically it's the CTL's job to kill those guys
Describe the mechanism for ADCC
- IgG binds to target cell
- NK cells binds to Fc end of Ab using it's receptor
- NK cell now triggered => send lethal signals to target
Often the Ab used is a monAb
Discuss the use of growth factors in BM transplantation
G-CSF and GM-CSF are used in BM transplants
sorry, not sure what else to say here
Describe how a monoAb against a T cell surface molecule could enhance the activity of a CTL
- Remove T cells => transform them using lentivirus vectors with *chimeric Ag receptor*
- Ab linked to CAR
- Allows for a transformed CTL to bind to a tumor target w/ high affinity and chosen specificity