(L23) Adaptive Antigen Recognition in the Immune System Flashcards
What are the components of the BCR complex?
What is responsible for Ag binding and what is responsible for signal transduction?
L23 S8
Membrane bound IgM or IgD:
- Ag binding
- nonsignal transducing (no ITAMs)
Igα and Igβ:
- signal transducing (ITAMs)
- non-Ag binding
What are the components of the TCR complex?
What is responsible for Ag binding and what is responsible for signal transduction?
L23 S9
TCR:
- Ag binding
- nonsignal transducing (no ITAMs)
CD3:
- two complexes (εγ and εδ)
- signal transducing (ITAMs)
ζ dimer:
-signal transducing (ITAMs)
Describe the state of the BCR/TCR at the stages of pro-lymphocyte, pre-lymphocyte, and immature lymphocytes.
L23 S10
Pro-lymphocyte:
-no receptor
Pre-lymphocyte:
-BCR heavy chain or TCR β chain present with surrogate light or α chain
Immature lymphocyte:
-complete BCR and TCR
What are the mechanisms of lymphocyte receptor diversity?
L23 S14
Combinatorial diversification:
- multiple different copies of gene
- V(D)J somatic recombination
Junctional diversity:
-addition of P and N nucleotides at junctions between V, D, and J segments
Somatic hypermutation:
-induced point mutations in V(D)J regions (only in B cells)
What enzyme is responsible for V(D)J recombination?
L23 S22
RAG-1 and RAG-2
Only present in lymphocytes
Enzymes select V/D/J copies that will be used, excise DNA of copies that were not selected, and joins ligates DNA so selected copies are adjacent.
How are BCR heavy chains and TCR β chains rearranged?
L23 S20
D and J segments are selected and rearranged first
V and DJ segments are selected and rearranged second
How are BCR light chains and TCR α chains rearranged?
L23 S27
Light chains and alpha chains do not have diversity (D) segments
Only VJ selection and rearrangement occurs
How is junctional diversity created?
L23 S24-25
Recombination cleaves hairpins asymmetrically leaving some overhanging nucleotides.
Terminal doxyribonucleotidyl transferase (TdT) uses overhanging nucleotides as template to created palindromic (P) nucleotides.
TdT then randomly generates N nucleotides to fill gap between strands
How are Cμ or Cδ selected to make both μ chains and δ chains for BCRs?
L23 S40
Pre-mRNA which contains VDJ segment and non-adjacent copies of both Cμ and Cδ.
Either the Cμ or Cδ is selected and placed adjacent to the VDJ segment resulting in mRNA for a μ chain or a δ chain
How are B cells developed and selected?
L23 S41
Heavy chain is produced first and presented with surrogate light chain. If this fails, cell death occurs.
Cells that successfully produced a heavy chain then produce a κ light chain. If this fails, cell death occurs.
Cells that successfully produce both heavy and light chains are then tested for auto-reactivity.
Nonself reactive B cells are positively selected while self-reactive B cells are negatively selected and undergo BCR editing
What is BCR editing?
Why and how does it occur?
L23 S42
B cells that are self reactive cannot be allow to survive.
Initially the BCR was created using the κ light chain (there are two light chain loci κ and λ)
If BCR with the κ chain is self reactive, that chain is disposed of and recombination reoccur using the λ chains this time.
New BCR with λ light chain is tested again. If still self-reactive, cell death occurs.
How are T cells developed and selected?
L23 S41
β chain is produced first and presented with surrogate α chain. If this fails, cell death occurs.
Cells that successfully produced a β chain then produce a α chain. If this fails, cell death occurs.
Cells that successfully produce both β and α chains are then tested for auto-reactivity.
Nonself reactive T cells are positively selected while self-reactive T cells are negatively selected undergo cell death
What stages of CD4, CD8, CD3 expression do T cells go through and where are they located?
L23 S55-56
CD3-, CD4-, CD8- (pro-T cell):
-occurs from bone marrow to subcapsular zone
CD3+, CD4+, CD8+ (double positive immature T cell w/ TCR):
-occurs in cortex
CD3+, CD4+, CD8- or CD3+, CD4-, CD8+ (single positive w/ TCR):
-occurs in the medulla and in circulation