Molecular Basis of Ag Recognition Flashcards
Which receptor can only recognize peptides presented by APC?
TCR
What are the subunits of BCR?
IgAlpha and IgBeta
What kind of antigen can be recognized by BCR?
lipids, proteins, carbs= Macromolecules
Effector function of BCR
Fc region of Ab
One one of the VLCL and VhCh alleles are expressed in single B cell what is this process called?
allelic exclusion; also governs expression of TCR
How are variable regions of receptors determined?
rearrangement of DNA
3 mechanisms of creating epitope-specific diversity?
Somatic recombination, mRNA splicing, and junctional diversity
What initiates TCR or BCR rearrangement?
somatic recombination: includes deletion and reannealing
name of genes that encode enzymes performing recombination of BCR and TCR during process of VDJ recombination
RAG 1 and RAG 2= recombination-activating genes 1 and 2
during what stages are expression of RAG genes restricted to?
developmental stages of B and T lymphocytes
How many gene segments does heavy chain have in chromosome 14?
4: VDJC; multiple copies of each so as to create variance
BCR recombination sequence of events
- D & J chosen; extra DNA deleted
- V segment chosen; extra deleted
- J chosen; DNA between VDJ and C deleted
Name for producing rearrangement that does not contain stop codons
productive rearrangement
Once productive rearrangement is confirmed what happens?
recombination of other gene is stopped
If Vh rearrangement is productive then what occurs with B cell?
proliferates and “takes care” of VL
how many tests of productive rearrangement occur?
2
Where is junctional diversity generated?
points between joining genes
Where are P nucleotides derived from?
asymmetric opening of hairpin loops
How does junctional diversity result?
loss of nucleotides (exonucleases) and addition of N and P nucleotides
What aids addition of N nucleotides?
Terminal deoxynucleotidyl transferase (TdT)
TCR gene rearrangement
slide 20, 21
Omenn syndrome results as a defect in what?
autosomal, missense mutation, partial rag1/2 activity
What are the symptoms of Omenn syndrome?
lack of b cells, marked decrease in T cell count, severe immune deficiency with failure to thrive, diarrhea, red rush
SCID results as a defect in what?
autosomal, null mutation in rag1/2 genes, no enzymatic activities
Symptoms of SCID?
total lack of T and B cells, defect in both humoral and cell-mediated immunity
Name for lack of reaction?
anergy
T cell needs what 2 things for activation
MHC binding and co-stimulator binding
binding of co-stimulator only has what effect on t cell?
none
binding of MHC only has what effect on t cell?
anergy
Activated APCs express high levels of?
MHCII and co-stimulatory molecules B7-1(CD 80) and B7-2(CD 86)
What does protein B7 on APC interact with on T cells?
CD28
Close contact between T cell and APC? what does it help ensure?
Immunological Synapse; ensures effector molecules (cytokines) are not affecting bystander cells
3 pairs of molecules that interact in immunological synapse?
TCR/MHC-peptide
Co-stimulator B7 and CD 28
Adhesion LFA-1/ICAM-1
T Cell accessory molecules
slide 27
Plasma cells are mostly found where?
in lymphoid organs
B cells act as what to T cells?
Pro-APCs
What is the coreceptor for BCR?
CD 19; can be used as specific marker of B cells
What are the two mechanism of B cell activation:
Thymus independent and dependent
TD Ags activate B cells with assistance of what?
T helper cells
Steps of TD activation of B cells:
- Antigen binding to BCR
- Helper Th2 cell signal thru CD40 ligand and cytokines
- B cell proliferates and differentiates
How do BCRs bind to TI Ags?
repetitive epitopes on bacterium multiple BCRs bind= cross-linking= generates signal
What transduces signal from BCR to inside cell?
IgAlpha and IgBeta
What process must the signaling molecules undergo in TI Ags recognition
enzymes attached to the cytoplasmic portion of IgAlpha and IgBeta catalyze phosphorylation
