lecture 4- generation of antibody diversity Flashcards
___ is any molecule that enhances phagocytosis by tagging it for binding to a cell surface receptor
opsonins
antibodies are also strong ___ and bind ___ on phagocytes
opsonins
Fc receptors
___ is the process by which bacteria are altered by opsonins so as to become more readily and more efficiently engulfed by phagocytes
opsonization
What is the difference between an antibody being able to activate complement and act as an opsonin?
IgG can do both -different receptors- complement receptor and Fc receptor
the human genome has how many genes?
~30,000
3 types of gene segments: ___
2 types of light chains available: ___
V, D, J
lambda and kappa
generation of antibody diversity is due to: (first 3)
1- combinational diversity
2- junctional diversity
3- somatic hypermutation
in all cells except for developed lymphocytes, immunoglobulin DNA exists in ___ configuration
all loci are on ___
germline
3 different chromosomes
after heavy chain undergoes recombination, light chain undergoes rearrangement, what happens here?
allelic exclusion- only one BCR expressed by a B cell
describe the sequence of events during VDJ recombination
(these steps happen over and over and are irreversible)
1- synapsis: bends linear DNA, recombination signal sequences come together (synapsed) so they can be cleaved
2- cleavage: done by RAG1 / RAG2 – generates double strand breaks in DNA, form into hairpin loops
3- hairpin processing: Artemis opens hairpins at coding ends
4- joining: non-homologous end joining done by Ku70, Ku80, and DNA ligase
describe junctional diversity
- the same VDJ segment usage can generate antibodies that have different AA sequences
- through addition of nucleotides, diversity is further increased
- occurs at the CDR3 region, allowing greater variability than that encoded by
gene segments - mediated by TdT enzyme- adds nucleotides in junctional region between gene segments
describe the nucleotide addition in junctional diversity
- P nucleotides are put in, complementary to loose uneven ends when hairpins were cleaved
- N nucleotides are additional nucleotides added to both strands- results in differences in length of nucleotides, could potentially change reading frame (complementary)
name 2 reversible and regulated steps for changes in antibody genes during a B cells’ life
1- transcription activated with coexpression of surface IgM & IgD
2- synthesis changes from membrane Ig to secreted antibody
** both reversible because RNA splicing - not changes in genomic DNA