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Molecules of Specific Recognition
Lecture 6 (8.24.09)
29
Medical
Professional
09/11/2009

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Term
immunogen
Definition
subset of antigens actually able to induce an immune response; the immunogenecity of an Ag is determined by the induction of the innate arm with adjuvants, induction of adaptive immunity, and discrimination of self/nonself
Term
what is the most common TCR heterodimer?
Definition
a-B
Term
which Ig domain is variable?
Definition
the VH & VL, which are the initial loops closest to the N terminus of the Ig protein
Term
what connects Fc and Fab?
Definition
the hinge region
Term
what region of receptor binds antigen?
Definition
CDR, the concentrated areas of genetic variability (short amino acid sequences/loops). There are 12 CDRs/per non-IgM immunoglobulin (3 CDRs/chain). The CDRs are located in the VL and VH of the Ig. CDR1, 2, and 3.
Term
framework regions
Definition
in the variable region of the Ig, but do not bind antigen. help in maintaining structure. each chain has 4 FWRs and 3 CDRs
Term
what molecules enable signal transduction?
Definition
Ig-alpha and Ig-beta
Term
why are hinge regions so important?
Definition
enable the Ig to bind to multiple repetitive epitopes in different configurations, bc they can stretch apart or close together, as needed
Term
what does the aB-TCR bind?
Definition
a composite antigen: a peptide fragment bound to MHC proteins; may only bind linear peptide antigens
Term
describe structure of TCR chains
Definition
each chain contains 1 variable and 1 constant domain; V domain binds antigen, and C domain anchors TCR to membrane
Term
what is neutralization and what Abs mediate it?
Definition
neutralization is the Ab binding of microbe/toxin to prevent its entry/infection of cells and tissues. IgA, IgG, IgM are all involved in neutralization
Term
which Fc receptor is inhibitory?
Definition
Fc-gamma-IIB receptor has an ITIM
Term
what Ig is the most potent activator of complement?
Definition
IgM (due to its pentamer status)
Term
how is mucosal transport of IgA mediated?
Definition
poly-Ig receptor
Term
what produces IgA and the J chain?
Definition
B cell
Term
what produces the poly-Ig receptor?
Definition
the epithelium
Term
what purpose does the J chain?
Definition
every Ab produced by B cells, associates with a J chain; most likely necessary for mucosal secretion, since IgA dimerizes before binding with poly-Ig receptor
Term
how does IgA get into lumen?
Definition
travels with poly-Ig receptor inside mucosal epithelial cell; after a proteolytic cleavage, the poly-IgR/IgA complex exits into lumen
Term
FcRn
Definition
neonatal FcR; fetal and neonatal transport of IG is mediated by the FCRn
Term
why is IgM always the first Ig produced?
Definition
on chromosome 14, where all the genes for the 9 isotypes resides, the gene for IgM is the first one in the sequence, is therefore the first to be transcribed.
Term
why can IgM and IgD be expressed simultaneously?
Definition
the isotype choice between IgM and IgD (the second genes) is decided at the level of transcription via alternative splicing. as such, a B cell can express both simultaneously
Term
how are all other istotypes generated?
Definition
IgG, IgA, IgE are all produced via DNA recombination/isotype heavy chain switching
Term
what is the purpose of the switch region?
Definition
a DNA sequence located after the C(m) gene [Sm]and BEFORE each of the Cg [Sg], Ca [Sa], Ce [Se]--mediates the recombination by looping out the intervening DNA sequences, resulting in a permanenent switch of a C gene from one isotype to another
Term
AID
Definition
activation-induced cytidine deaminase: a DNA deaminating enzyme ABSOLUTELY REQUIRED for BOTH class switching [constant domains] and somatic hypermutation [variable domains]
Term
when does class switch occur?
Definition
in the late stage of B cell development after antigen exposure, in response to various signals provided by t cells in the lymphoid follicles; mediated by cytokines that induce switching to particular isotypes
Term
Fc-gamma-II receptor
Definition
on NK cells; permits identification of target cell coated with Ab, tagged for killing; target cell is killed by cytotoxic compounds released by NK cell

IgG1, IgG3 mediate NK dependent ADCC
Term
what Abs arecomplement-fixing?
Definition
pentameric IgM
IgG1, IgG3
Term
when does IgA present as a dimer?
Definition
in serum, IgA is a monomer
in secreted fluids and in mucosa, IgA is a dimer associated with the J chain (both produced by B cell that reside in the gut lamina propria, respiratory tract, and urogenital tract)
Term
how is transport of IgG1 and IG3 mediated from mom into fetal circulation?
Definition
IgG1 and IgG3 across the placenta and neonatal intestinal epithelium into blood circulation is mediated by NEONATAL Fc RECEPTOR (FcRn).

in newborns, both maternal IgA and IgG are passed through breastmilk
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