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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?

Fully human!

- 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


Discuss the use of modified (drugs, isotopes) monoAbs in tumor diagnosis or therapy

- monoAbs can be targeted to specific tumor cells
- Some activate complement=> tumor lysed/phagocytosed
- More invoke ADCC
- can also be tagged w/ a poison or radioisotope

radioisotope tagging is used in diagnosis