5 - B and T cell Devo Flashcards
All lymphoid neoplasms (B and T cells) are derived from _____ ______ _____ and are ______.
All lymphoid neoplasms (B and T cells) are derived from transformed single cells and are clonal.
B and T cells undergo what type of rearrangement?
Antigen receptor gene rearrangement. This almost always occurs before transformation.
Thus, the clonal malignant B or T cells can be identified by their unique antigen receptors.
How can we identify malignant T or B lymphocytes in a patient?
By analyzing the antigen receptor genes.
And, if a large population of clonal cells is present, this information can be used to differentiate clonal neoplasms from polyclonal pathologic processes.
In what primary/generative lymphoid tissue do B and T cells develop?
B lymphocytes are generated in the bone marrow.
T lymphocytes are generated in the thymus.
What are the two functions of the antigen receptos of B and T cells?
- Bind epitopes in a highly specific manner
- Trigger responses in the lymphocytes in which they are expressed
Describe how T and B cell antigen receptors bind chemically different epitopes?
BCRs bind non-degraded antiens of many types (proteins, lipids, carbs, and nucleic acids)
TCRs bind complexes of MHC molecules and peptides (degraded proteins)
Are immunoglobulins membrane bound or secreted? Are TCRs membrane bound or secreted?
Immunoglobulins may be membrane bound of secreted.
TCRs are membrane bound but NOT secreted.
How does antibody (immunoglobulin) recognize its antigen? What is responsible for it’s effector function?
Via the variable (V) region of heavy and light chains of membrane Ig.
The constant region (C) of the secreted Ig mediates the effector function.
How does the TCR recognize its antigen? What is responsible for it’s effector function?
Antigen is recognized by the variable (V) regions of the alpha and beta chains.
TCR does not perform effector funcitons.
What are the names of the green regions on the immunoglobulin?
Blue box is the variable region where the antigen binding occurs on the N terminus.
C terminus is the constant where theeffector function lies.
What is the structure of the B cell antigen receptor?
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).
Each immunoglobulin variable region (heavy and light chain( have 3 regions of what?
Hypervariability (complementary-determining (CD) regions).
These are contact sites for the epitope in the antigen binding site.
What is the function of:
- IgA
- IgD
- IgE
- IgG
- IgM
- IgA: mucosal immunity
- IgD: Naive B cell antigen receptor (transiently expressed)
- IgE: Mast cell activation (immediate hypersensitivity) and defense against helminths/parasites
- IgG: opsonization, complement activation, ADCC, neonatal immunity, feedback inhibition of B cells
- IgM: naive B cell antigen receptor, complement activation
What are isotypic differences?
Differences in the heavy chain and constant regions.
If an animal is immunized with human Ig, it will generate an antibody response to the non-self protein. Abs direct againt common epitopes on a given isotype will react with the same isotypes from any human. For example, anti-IgG Abs will react with all human IgG molecules.
What are allotypic differences?
Small differences due to polymorphisms in the heavy and light chain constant regions (differences between people)
These are generally single amino acid interchanges. They may also serve as epitopes. Antibodies will be present that will react specifically with allelic variants. For example, individual A may have an allelic variant in his IgG heavy chain that is not present in person B. Antisera that distinguish the IgG from these two people are called anti-allotypic. Anti-allotypic antibodies are common in pts with RA.
What are idiotypic differences?
Differences in antigen binding (specificity)
Epitopes associated with the variable regions of antibodies are unique to a given antibody; these are the antigen-binding regions of the antibody. Antiodies reactive with these epitopes are called anti-idiopathic and may be used to identify B cells from an individual with a B cell tumor.
What is the structure of a T cell antigen receptor?
Two chains: an alpha and a beta chain.
Only a single constant resion and a single variable region.
Variable region forms the antigen binding site.
What is the sequence of Ig and TCR gene rearrangement events?
Ig Heavy chain or TCR Beta chain: VDJC
Ig Light chain or TCR a chain: VJC
What happens if there are mutations in the recombination enzymes such as VDJ recombinase, RAG-1 and RAG2?
This results in the failure to make T or B cells.
Causes severe combined immunodeficiency disease (SCID).
What interleukin helps maintain progenitor lymphocytes?
IL-7
What are the 5 steps in the maturation of lymphocytes?
- Proliferation
- Pre-B/T antigen receptor expression
- Proliferation
- Antigen receptor expression
- Positive and negative selection
What are the 7 steps in the maturation and selection of B lymphocytes?
- Stem cell
- PRo-B
- Pre-B
- Immature B
- Mature B
- Peripheral lymphoid tissues
- Activated B cells secrete antibodies
T cell maturation and selection occurs in the _______? Where does positive and negative T cell selection occur?
Thymus!
Positive selection occurs in the cortex of the thymus, negative selection primarily occurs in the medullary region of the thymus.
Describe positive and negative selection of T cells?
Positive: thymocytes reactive with self MHC are expanded following interaction with self-MHC peptide complexes in the thymus.
Negative: self-reactive thymocytes are eliminated, either physaically or functionally, following interaction of the T cell antigen receptor with self MHC-peptide complexes.
