Dr. Empey Lectures Flashcards
(18 cards)
What is an antibody?
Protein that recognizes antigens and initiates an immune response
What are the functional components of an antibody?
Fab(fragment antigen binding) and Fc(fragment crystallizable), complementary determining region(CDR), framework regions, hinge region and disulfide bonds
What is the importance of the complementary determining region(CDR)?
Has almost an infinite variance of possible amino acid sequences which allows for wide range of ag recognition
What are the 3 Fc mediated biological functions
Direct cellular killing(ADCC and CDC), Fc-mediated degranulation, transport/recycling
Describe Antibody-dependent cell mediated cytotoxicity(ADCC)
Ab binds to ag, NK cell Fc receptors recognize cell bound ab, degranulation into lytic synapse, cell dies via apoptosis
Describe complement-dependent cytotoxicity(CDC)
Ab bind to ag, multiple pathways elicit complement cascade and complement bind to ab(innate immunity), initiate membrane attack, cell dies via lysis
Describe Fc-mediated degranulation
IgE mediated degranulation of eosinophils and basophils
Describe transport and recycling
Receptor mediated transport across placenta and into breast milk, recycling via FcRn
Describe the transport function of the FcRn(Brambell Receptor)
IgG can bind to FcRn in neonatal intestinal lumen with acidic pH then be released into neonatal blood, IgG can be engulfed from maternal blood, bind to FcRn in endosomes and be released into fetal circulation
Describe recycling function of FcRn(Brambell Receptor)
IgG that is bound to FcRn is protected from the acidic environment of the endosome and therefore can be salvaged/recycled
Describe the monoclonal ab with the greatest risk of immunogenicity(highest to lowest)
Murine ab(HAMA), Human anti-chimera mAb(HACA, 66% human), Human anti-humanized mAb(HAHA, 90% human), Human anti-human mAb(HAHA, 100% human)
What is the naming schema for mAb?
prefix from industry, u=tumor k(i)=interleukin s(o)=bone vi=viral, o=mouse u=human xi=chimeric zu=humanized, -mab
What is the breakdown of Palavizumab?
Pala-(virus)-(humanized)-mab
What are types of unwanted immune responses?
isotypic(between species), allotypic(within species), idiotypic(within individiuals)
How can mAb block the immune response?
CDR controls mAb antagonism, bind to ligand or to receptor, prevent stimulation by ligand via receptor
How can mAb induce immune response?
Induce cell death via ADCC, CDC, or apoptosis, induce immune functions (complement binds to Fc region or Fc receptors bind to Fc region, both induce cell lysis)
Describe Ab dependent cellular apoptosis
Rituximab, binds to CD20 on surface of lymphocytes, crosslink Rituximab to CD20 which induces cellular apoptosis
What are drug-free macromolecular therapeutics(DFMT)?
Leveraging mechanism by amplifying CD-20 cross-linking to enhance Rituximab-resistant cells
