Adaptive Antigen Recognition Flashcards
What is the basic structure of a BCR?
surface immunoglobulin and two invariant chains (alpha and beta) which function in signal transduction
What is the basic structure of a TCR?
Alpha:beta heterodimer that associates with invariant sequence
Associated proteins form CD3 complex for signaling
What does allelic exclusion mean?
monospecific= make sure allele is specific for only one epitope
What is clonal selection?
Gene rearrangement events in the absence of antigen, build antibodies
Lymphocyte clones with diverse receptors enter tissue and antigen-specific clones are selected by antigens for antigen immune response
What is the process of V(D)J Rearrangment and Junctional diversity in BCRs/Antibodies? What enzymes are involved?
mu Heavy Chain: Take a random D and a J and join= DJ –> at junction between D and J insertion then add a random V= VDJ which goes on to be transcribed and translated (same process in light chain but no D region)
RSS recognizes palindromic sequences and makes cuts creating hairpin.
RAG-1 and RAG-2 cut out hairpin for both DJ and VDJ. When putting back together TdT puts in nucleotides leading to hypervariable region= somatic recombination
What is the process of What is the process of V(D)J Rearrangment and Junctional diversity in TCRs? What enzymes are involved?
Same as in BCR except heavy chain= beta chain and light chain= alpha chain
Take a random D and a J and join= DJ –> at junction between D and J insertion then add a random V= VDJ which goes on to be transcribed and translated (same process in light chain but no D region)
During this process RSS recognizes palindromic sequences and makes cuts creating hairpin.
RAG-1 and RAG-2 cut out hairpin for both DJ and VDJ. When putting back together TdT puts in nucleotides leading to hypervariable region= somatic recombination
What happens when a stem cell proliferates to a Pro-B cell?
Induced by IL-7
Cd19+ begins to be expressed
Still in bone marrow, no Ig expression, unrecombined DNA, or antigen response
What happens when a pro-b becomes pre-b?
Upregulation of RAF and TdT
Heavy chain of IgM from mu mRNA with surrogate light chain
Still in bone marrow, no Ig expression, and no antigen response
What happens when a pre-b becomes a immature B
Proliferation event
Means the surrogate light chain works so the production of the real light chain happens and surrogate light chain transcription shut off
Inhibition of H chain recombination= allelic exclusion, b cell can express one heavy chain encoded by only one of the two inherited alleles
IgM on membrane
What happens when immature B becomes mature naive B?
Alternative splicing of heavy chain RNA becoming either mu or delta
Membrane expresses IgM and IgD
Moves to spleen for more maturation
What are the checkpoints in B/T-lymphocyte development?
Pro-B/T to Pre-B/T= if don’t express preantigen receptor then cell death
Pre to immature= if surrogate light chain not working then cell death
Receptor Editing/ Distinguishing self from non-self:
no self reaction/ weak recognition of MHC= migrate to periphery
respond strongly, multivalent self antigen-=apoptosis, clonal deletion
soluble self-antigen = rescued B CELLS ONLY
How are B cells rescued?
RAG protein allows for additional rearrangement of light chain genes, if new light chain not reactive with self-antigen then B-cell will mature if not then apoptosis
Where do T cells develop?
In the stroma of the thymus, go from cortex to medulla during development
Enter end exit via BLOOD because thymus primary lymphoid organ
How to stem cells become pro-t cells?
Move from bone marrow to cortex of stroma of thymus via stimulation by IL-7 after proliferates
c-kit+ expressed on surface
What happens when pro-t goes to pre-t?
increases in TdT expression (huge surge so more diversity in T-cells) and RAG
recombined B chain 1st (VDJ and constant) and put on surface with surrogate alpha
