HDM -Chapter 4 Flashcards
What type of peptides do TCR’s recognize?
Small LINEAR Peptides and they must do in conjunction with CD3 and MHC receptors
Where are the variable regions and in the BCR and TCR receptors?
BCR: NH-Terminous of H and L chains
TCR: NH-Terminous of Alpha and Beta
Where were the first immunglobulins found?
Found in the serum
Where is the flexible region found on Ab?
Between the CH2 and CH1
What is the basic structure of an Ab?
An antibody is composed of 2 heavy and 2 light chains
Bound by disulfide bridges/noncovalent interactions
Both contain V and C regions
Frgamentsof Ab:
Fc (fragment constant)
Fab (Fragment Ab)
What is an enzyme that can cleave an Ab into fragments?
Papain will create two Fab and 1 Fc, Pepsin 2 Fabs only
What are the five different Heavy chains of Immunoglobulins? L-chains?
Heavy Chains: Alpha (IgA), Gamma (IgG), Mu (IgM), Delta (IgD), Epsilon (igE)
L-Chain: Kappa and Delta
Where are the interchain disulfide bridges and loops(Domains)?
There are interchain disulfide bridges evry 90 AA’s
Loops every 100 VH, VL, CH1 and CH2 etc.
What is the difference between the IgM as a receptor and IgG as secreted Ab?
The Membrane bound IgM has an extra Constant region and a C-Terminal Cytoplasmic domain
What is affinity of Ab’s?
What is affinity maturation?
Affinity is the strength of the binding between the Ag ad Ab
Affinity maturation: In a secondary Immune response the affinity is increased
What does BRC associate with to make a BCR Complex?
Complexes with Ig-alpha and Ig-beta which will transmit the signal into the cell
How do we create a Monoclonal Ab?
- Take a B-cell and fuse with a myeloma cell (tumor of plasmacells) -> hybridomas
- Isolate clones derived from a single hybridoma
3 Screen supernats for the antibody of choice and expand
How do we use mouse monoclonal Ab’ so we avoid a reaction to the mouse portion ?
If the Fc Region of a Monoclonal Mouse Ab with a human Fc Region then there is little to no RXn w/in the host
What is the main cytokine that is used as a growth factor in the development of T and B Cells? By what cells?
IL-7 by stromal cells within the Bone Marrow and thymus
Explain positive and negative selection of T cells?
Positive selection refers to the process of keeping specific cells that recognize MHC receptors
Negative Selection Is when cells that recognize self
What do V, D, J and C stand for with the genes of Ig and TCR’s?
V= Variable
D =Diversity
J = Joining
C = Constant
Explain VDJ recombination.
RAG 1/2 enzymes recognize sequences in the D and J recombination sites creating a DJ segment with VDJ recombinase protein
RAG 1/2 then bind to the V and the new DJ fragment and recombine
Make the primary RNA transcript, and then the exons of VDJ and Mu ‘5 C region to make a IgM BCR
Involved double stranded breaks of DNA that are stabilized by RAG’s
How is recombination regulated?
RAG 1/2 are only expressed early on in developmentof T and B cells so that we stick to the single recombined gene. Also in T cells we only have access to the DNA of the TCR genes and in B-cells we only have access to the Ig genes.
What are the three ways to increase diversity in receptors?
- Exonuclease that will randomly remove some nucleotides prior to combining segemnts
- TdT will randomly add nucleotides between the V, D and J segments
- Before the double stranded breaks are repaired the P-nucleotide will randomly add more nucleotides
What is the most variable loop of the Constant region?
CDR3
What are the five stages of B cells development?
Stem Cell Pro-B Pre-B Immature B Mature B
What are the three things the Pre-BCR does?
- Signalling of Pre-BCR will signal the cell to the proliferate because the heavy chain is stable
- Shuts off the genes of the other heavy chain, alleleic exlusion only represents
- Triggers the rearrangement of the Kappa light chain
What is receptor editing?
When a B-cell in the bone marrow binds to a antigen in the bone marrow with high affinity the cell will undergo editing of the Lamda light chain and do further VJ recombination
What is the cytokine that is important for T-cell development?
IL-7