Generation of Lymphocyte Antigen Receptors Flashcards
Where do T & B Lymphocytes Develop?
B cells leave bone marrow as immature cells
T cells move from bone marrow to the thymus where they mature and then leave
What do the antigen receptors of B and T cells do?
- Bind epitopes in a highly specific manner
2. Trigger responses in the lymphocytes in which they are expressed.
B cell receptors bind what kind of chemical isotopes?
B cell receptors bind non-degraded antigens of many types (proteins, lipids, carbohydrates, nucleic acids, etc.)
T cell receptors bind what kind of chemical isotopes?
T cell receptors bind complexes of MHC molecules and peptides (degraded proteins)
The antigen receptors require additional components to do what?
transmit signals to the interior of the cell
The antigen receptors of lymphocytes have variable and constant domains that do different things what are they?
variable domains that form the antigen binding site and constant domains that maintain overall structure.
Are immunoglobulins membrane bound or secreted?
can be BOTH
Immunoglobulins are made of what kind of chains that recognize antigens?
variable heavy and light chains
T cell receptors are made of what kind of chains that recognize antigens?
variable regions of alpha and beta chains
What is the structure of IgG Ab?
Fab region and Fc region
- There are 5 different classes (isotypes) that are functionally different due to constant region differences
- light chains are either kappa or lambda (does not change during class switching)
What are the Major Isotypes (Classes) of Antibodies?
IgA, IgD, IgE, IgG and IgM
EACH IMMUNOGLOBULIN VARIABLE REGION (HEAVY AND LIGHT CHAIN) HAS 3 REGIONS OF HYPERVARIABILITY THESE ARE CONTACT SITES FOR what?
THE EPITOPE IN THE ANTIGEN BINDING SITE
What are the functions of the major classes of Ab?
IgA: mucosal immunity
IgD: naive B cell
IgE: mast cell activation and defense against parasites
IgG: opsonization, completment, ADCC, neonatal immunity
IgM: naive b cell and completment
What are allotypic Ab differences?
a difference in the constant region of the heavy chain of Ab that usually only differs by one AA within an isotype
What is an idiotypic Ab difference?
difference in variable region that dictates specificity
What is the difference between affinity and avidity?
affinity is the strength of a single binding interaction
avidity is multiple binding interactions eg: MHC needed the costimulatory interaction as well
What are some important features of TCRs?
made of alpha and beta chains
use AA chains bound to MHC and affinity does not change
CD4 or CD8 simultaneously bind MHC
What are some important features of Ig (aka B cell receptors)?
made of heavy and light chains
bind macromolecules and small chemicals and affinity increases throughout immune response
How is receptor diversity generated?
- COMBINATORIAL (MULTIPLE GENE SEGMENTS; VDJ)
- JUNCTIONAL DIVERSITY
- MIX AND MATCH PAIRING OF LIGHT AND HEAVY CHAINS
- SOMATIC HYPERMUTATION *
What are the three gene segments that recombine during cellular differentiation and maturation?
The first recombination event is the heavy chain D and J followed by recombination of V with DJ. VDJ then recombines with a constant region gene segment.
Then V and J then recombine and VJ recombine with a C segment to form a transcript for the light chain. light chain (or TCR alpha) then binds to heavy chain (or TCR beta)
Which cells have a greater diversity of receptors?
TCR > Ig
What is allelic Exclusion?
first heavy chain recombination event occurs on the maternal chromosome and is successful, the heavy chain genes on the paternal chromosome will not rearrange, and the cell will express the maternal gene product only. If the first rearrangement is not successful, rearrangement of the heavy chain genes on the paternal chromosome will occur. If successful, the paternal heavy chain gene product will be expressed. If neither is successful, the cell will die.
If Mutations in the Recombination Enzymes (VDJ recombinase) occurs what disease do you see?
autosomal SCID!
Steps in the Maturation of Lymphocytes:
Pro B/T cell needs to express on chain of antigen receptor (1st checkpoint) then expresses full antigen receptor (2nd checkpoint) then tested for self recognition
Mature B cells express what two forms of Ig?
mature have IgM and IgD
activated* B cells lose the IgD
As these have the potential for causing autoimmune pathology, B cells with autoreactive receptors must be removed or functionally inactivated. This process is known as what?
negative selection
Steps in maturation of T-cells?
Thymus is major site of maturation. Positive selection is reaction with MHC complexes then negative selection occurs if the cell recognizes self peptide within an MHC.
What are double positive T cells?
immature T cells expressing both CD4 and CD8 will undergo selection and then lose the CD molecule that wasn’t selected
All lymphoid neoplasms are derived from what?
single cells and are thereby clonal
clonal malignant B or T cells can be identified by their what?
unique antigen receptors
Clonal malignant cells can be identified in patients by analyzing the antigen receptor what?
genes in T or B lymphocytes. If a large population of clonal cells is present, this information can be used to differentiate clonal neoplasms from polyclonal pathologic processes
