Term
| What are the 2 phases of Ig synthesis and secretion? |
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Definition
1.Ig Expression During B cell maturation.
- Antigen-independent phase
2. Ig Expression After B cell activation with an Ag
- Antigen dependent phase |
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Term
| Explain the different parts of the antigen independent phase |
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Definition
(a) Ig gene rearrangement & recombinational events.
·Occurs during B cell development in the bone marrow
·Involves selection, recombination and assembly of gene segments to form a functional gene or transcription unit (i.e. a coding sequence) for L & H chains.
·Functional units for kappa, lambda & H chains arrange separately
·RAG-1 & RAG-2 gene encoded enzymes
·Activation of promoters and enhancers
(b)Transcription and translation of L & H genes results in a surface Ig, the B cell receptor for Ag |
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Term
| Explain light chain rearrangement |
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Definition
Light chain DNA undergoes V-J rearrangements
In gene rearrangement one of the V genes is randomly spliced to one of the J genes
This rearranged DNA then undergoes transcription and splicing to produce mature mRNA |
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Term
| Explain gene rearrangement for the H chains |
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Definition
Heavy chain DNA undergoes V-D-J rearrangements
It is two separate rearrangement events
A Dh (diversity gene) segment randomly joins to a Jh (joining gene) segment
Then the resulting DhJh segment randomly joins a Vh (variable gene) segment to produce a VhDhJh segment
This undergoes transcription and splicing to generate a mature mRNA |
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Term
| What are the basics of Ig expression events? |
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Definition
* IgM is the first Ig; closely followed by IgD. Alternate splicing of a primary mRNA transcript leads to IgM or IgD
* Other Ig classes are produced later, usually after Ag stimulation (step 2 during B cell activation.
* Each B cell (+ its clones) produces an Ab with a unique or distinctive Ag-binding specificity |
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Term
| Explain the antigen-dependent events of B cell activation |
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Definition
*Activation occurs when surface Ig binds its Ag.
*IgM is also the first Ig to be secreted.
*T cell help and cytokines function in activation, especially when other Ig isotypes are produced.
*Activated B cells divide and mature into antibody-secreting cells called plasma cells.
NOTE: Secreted Ig has the same Ag-binding specificity as the original surface-expressed Ig (changes occur at the Constant region of the H chain, CH, only |
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Term
| What is the difference between membrane Ig's and secreted Ig's |
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Definition
*Difference between Secreted Ig (sIg) & Membrane-bound Ig (mIg) is at the carboxy end of the H chain:
*The mIg has a transmembrane portion due to alternate splicing of a primary transcript that retains a small extra exon at the 3’ of the last constant domain |
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Term
| How are different classes of Ig's produced? |
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Definition
Class switching or isotype switch
- Usually it is from IgM (or IgD) to IgG, IgA or IgE
- Involves a second gene rearrangement/recombination event |
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Term
| What are the basics of class switching? |
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Definition
Class switching occurs after the V-D-J rearrangements
The VhDhJh segment can switch the Ch segment it is going to be transcribed with which switches the class of Ig
The mechanism is believed to involve formation of a DNA loop and the recombination involves the switch regions of the Ch genes |
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Term
| What is clonal selection theory? |
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Definition
*Theory explains Ag-specificity of Antibodies (Abs) during an immune response
*When an Ag enters the body, it is bound by only a few B cells equipped with the matching membrane Igs. These Ag-bound B cells are activated; they differentiate into plasma cells secreting only the Ab specific for the Ag. Possess same binding specificity as the membrane Ig |
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Term
| What are the mechanisms for generating Ig diversity? |
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Definition
Variable segments (V)
Diversity segments (D) - heavy chain only
Rare reading of D segments in 3 frames
Joining segments (J)
Joints with N and P nucleotides
Often somatic receptor mutations
Total diversity ~ 10^14 |
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Term
| What are the different mechanisms for T cell receptor (TCR) diversity? |
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Definition
Variable segments (V)
Diversity segments (D) - beta and delta only
Often reading of D segments in 3 frames
Joining segments (J)
Joints with N and P nucleotides
Total diversity ~ 10^18
Higher diversity (compared to Ig's) due to much increased numbers of J segments |
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Term
| What is the Ig superfamily? |
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Definition
Other immune molecules that
·Share Ig-like domain organization
·Most are involved in host defense
·Function as: receptors, co-receptors, cell-cell adhesion, inflammation, co-stimulation, cell activation, etc
ex's - TCR, MHC Class I and II, CD4, CD8 |
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Term
| Explain the major histocompatibility complex (MHC) |
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Definition
·HLA (human leukocyte Antigens)
·Located in chromosome 6 (except beta2M)
·2 major classes: Class I & Class II genes
·Mol bind Ag and present to T cell for activation
·Class I molecules/Ags: All somatic cells; Control CD8 T cells
·Class II molecules/Ags: Select cells (APCs, thymic epith); Control CD4 T cells
·Transplantation Ags: control graft rejection
·MHC restriction |
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Term
| What are the characteristics of the T cell receptor (TcR)? |
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Definition
·Receptor for Ag binding by T cells
·2 types: alpha-beta & delta-gamma TcR
·Genes rearranged during T cell maturation
·Enormous diversity of specificities
·Only bind Ag complexed with an MHC molecule
·Important for T cell recognition, activation & function |
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Term
| What is the structure of the T cell receptor? |
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Definition
It is a heterodimer composed of transmembrane chains alpha and beta.
Each chain contains a variable region (V) and a constant region (C)
They are connected by a disulfide bond in their hinge regions
Together they resemble a membrane bound Fab fragment of an Ig |
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Term
| How does gene rearrangement in the T cell receptor work? |
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Definition
The alpha chain undergoes VJ rearrangement similarly to light chain rearrangement
The beta chain undergoes VDJ rearrangement similarly to heavy chain rearrangement |
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Term
| What are the characteristics of co-receptors, adhesion, and co-stimulatory molecules? |
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Definition
·Important for immune activation and function; cellular interaction; inflammation
·APC-T cell interaction
·CTL-Target binding
·Signal transduction
·Representative co-receptors: CD3 complex, CD4, CD8, Ig-alpha, Ig-beta
* Representative co-stimulatory molecules: LFA-1 (integrin), CD2, CD28 (on T cells); ICAM-1, LFA-3, B7 on APCs) |
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Term
| What are the characteristics of cytokines, chemokines, and interleukin? |
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Definition
Important in immune initiation/ expansion, function, inflammation
·Growth factors, cell activation, immunoregulation
·Representative cytokines: Interleukin (IL)-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) |
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