Adaptive Antigen Recognition Flashcards
BCRs are composed of
Surface Ig and two invariant chains Iga, Igb- ensure surface expression of Ig and function in signal transduction
TCR composed of
a/b heterodimer
Associated proteins form CD3 complex- ensures surface expression of TCR and involved in signal transduction
Clonal selection
Gene rearrangement events occur in absence of antigen
Somatic hypermutation
Point mutations occurring in fully assembled VDJ regions during an immune response. Provides a significant source of Ab diversity
Does NOT occur in TCRs
Light chain gene rearrangement vs heavy chain
Light chain only has V-J segments, heavy chain has V-D-J segments
Heavy- first, D and J are joined, then V is joined to DJ
In TCRs- the beta chain has VDJ, the alpha chain only has VJ
RAG-1 RAG-2
Recombination activating genes, facilitate the joining of V, D and J segments
Junctional diversity
Insertion of a series of nucleotides, catalyzed by TdT
P nucleotides- added to asymmetrically cleaved hairpins in a templated manner
N nucleotides- added in non templated manner
-Leads to further diversity in the 3rd hypervariable region (idiotype)
Stem cell maturation into pro B cell
IL-7 tells stem cell–>pro B cell
Stem cell is only CD43+
Pro-B cell
CD43+ CD19+ CD10+ No Ig expression still Beginning to express RAG and TdT
Pre-B cell
Recombined H chain gene, u mRNA
Expresses Pre-B receptor associated u
CD43+
No response to Ag
Immature B cell
Expresses low amount of membrane IgM (u + kappa/lambda light chain)
CD43- negative
Response to Ag strong = negative selection, receptor editing
Response to Ag weak = positive selection
Mature B cell
Alternative splicing of VDJ-C RNA to form Cu and Cd mRNA
Expresses IgM and IgD
Activated by antigen recognition
Allelic exclusion
An individual B cell can express only one heavy chain encoded by one of the two inherited alleles
-Maintains clonal specificity
Signals from pre-BCR are responsible for
Largest proliferative expansion of B lineage cells during B cell development
Irreversibly inhibit rearrangement of Ig heavy chain (allelic exclusion)
Receptor editing
If there is reaction to self Ag, Light chains will be further rearranged by RAG
Does not occur in T cells
Where would you find immature CD3+4+8+ double positive thymocytes, and Mature single positive thymocytes
In the thymic cortex and corticomedullary junction for double positive immature
Thymic medulla/corticomedullary junction for mature
Stem cell T cell
Activated by IL-7 CD44+ ckit+ CD25- negative Located in bone marrow, migrates to thymus
Pro-T cell
CD44+
CD25+
ckit+
Pre-T cell
Recombined b chain gene Expresses Pre-T receptor w/b-chain/pre-Ta ckit+ CD25+ CD44- negative
Double positive T cell
Recombined b/a chain genes
Expresses membrane a/b TCR
CD4+, CD8+, TCR/CD3 expression low
Undergo positive/negative selection
Signals from Pre-TCR are responsible for
Stimulate a-chain recombination
Irreversibly inhibit rearrangement of b-chain locus on the other chromosome (allelic exclusion)
-Individual can only express one b-chain from one allele
Treg cells
Small population of self reactive CD4+ T cells become Tregs
Function to inhibit self-reactive Th1 cells in periphery
Express CD4 and CD25
FoxP3 transcription factor