Immjuno- genetics of immunoglobulins-test2
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- Expression of Ig genes - How is it similar and differet
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Ig genes go through normal transcription translation processessing as do other eukaryotic genes. mRNA are processed by cutting out introns and expressing exons. A 5'cap and 3' poly A tail is added.
There is a DIFFERENTIAL processing of mRNA with regard to the Heavy chain that determines whether the protein will be MEMBRANE bound or SECRETED
and that allows for SIMULTANEOUS IGM & IGD expression. - How do membrane and secreted IgG differ in the their gene expression
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Transmembrane IgMs express anchor residues and hydrophobic membrane spanning sequence
Secreted IgMs express "secreted" sequence with no expression of membrane spanning sequence -
Secreted Ig undergo the following steps:
1) Protein assembled along ______.
2) H / L chains assemble in ______.
3) Ig travels in vesicles to _____ and underges:
________of H chain
4) Vesicle leaves Golgi and fuses with ____ -
RER
ER
Golgi
glycosylation
plasma membrane - The only difference in membrane bound Igs.
- As the Ig travels from the ER to the Golgi it is anchored to vesicle membrane
- Describe co-expression of IgM and IgD and
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the primary transcript has BOTH IgM and IgD sequences.
The mRNA is ‘processed’ to remove one or the other. - Describe expression of Ig genes
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A mature (naïve) B cell will express IgM and IgD on it’s surface
Upon Ag recognition, the B cell can develop into a plasma cell and secrete the Ig OR a memory cell - Describe the life of a plasma cell
- focuses on secreting Ab (and then dies within a few days)
- Describe the life of a memory cell
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memory cell will usually CLASS SWITCH (dependent upon cytokines)upon next Ag exposure, B cell can develop into plasma cell secreting another IG ISOTYPE
SOMATIC HYPERMUTATION will occur with selection of higher affinity Abs - Describe class switching of Ig genes
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Occurs in H chain – constant region genes
Controlled by cytokines
-Switch factors: mostly produced by Th cells that cause a B cell to rearrange Ig CH genes
not completely understood - In class switching of Ig genes the _______ is induced to become a ________ and then a __________
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Activated B cell (centroblast)
Proliferating B cell (centrocyte)
Plasma cell - What are the PROLIFERATING cytokines involved in turning an activated B cell to a Proliferating B cell
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IL-2
IL-4
IL-5 - What are the DIFFERENTIATION cytokines involved in turning a proliferating B cell into a IgG2a or IgG3
- IFN-gamma
- What are the DIFFERENTIATION cytokines involved in turning a proliferating B cell into a IgA or IgG2b
- TNF-Beta
- What are the DIFFERENTIATION cytokines involved in turning a proliferating B cell into a IgE or IgG1
- IL-4
- What are the DIFFERENTIATION cytokines involved in turning a proliferating B cell into a IgM
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IL-2
IL-4
IL-5 - Describe Class switching of genes
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Once switch to a downstream isotype, cannot go back. In other words a B cell can never produce an upstream isotype.
Cytokines play the major role in class switching.
Th1 and Th2 cells produce different cytokines
these “classes†of cytokines play a role in determining which isotypes are most needed:
-IgA in secretory areas
-IgG to cross the placenta
-IgE against multicellular pathogens (parasitic worm, allergies)