Diversity vs. Specificity: Immunoglobulins Flashcards Preview

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Flashcards in Diversity vs. Specificity: Immunoglobulins Deck (41):
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immunoglobulin

aka antibody

can be membrane bound or secreted

all antibodies made by a single cell and have specificity

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immunoglobulin structure

two identical heavy and two identical light chains

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IgM

surface bound antibody

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Immunoglobulin superfamily

IgM, T cell receptor, MHC (HLA) and Ig-alpha/Ig-beta

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clonal selection

gene rearrangement events in the absence of antigen
-in bone marrow or thymus

clone has single specificity

10'7 - 10'11 different clones possible

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primary immunoglobulin rearrangement

multiple germ line genes
-combinatorial diversification

junctional diversity
-addition of nucleotides during process of joining

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secondary immunoglobulin rearrangement

somatic hypermutation
-point mutations occur in the fully assembled VJ and VDJ regions

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somatic hypermutation

happens during the immune response

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IL-3

secreted by T cells

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IL-7

necessary for commitment to lymphoid lineages

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location of heavy chain

chromosome 14

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two different light chains?

kappa and lambda

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3' end of gene?

C (constant regions)

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5' end of gene

V (variable regions)

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what contains D regions?

Ig heavy chain and TCR beta chain

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how many V regions in heavy chain

about 100 V regions

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different C regions of heavy chain determine what?

determine the isotype of the Ig

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what genes in the heavy chain?

many C regions (9 classes)
-exon for domain and the hinge region

many V regions, J regions, and D regions

**Exons expressed / introns not expressed

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what is in the kappa light chain?

only one C region

V regions have a leader exon and a V exon

several J regions between the V and C regions

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lambda light chain

4 C regions (with interspersed J regions)

around 30 V regions
-each has a leader region and V region

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allelic exclusion

have these genes on both mom and dad gene

express only mom/dad heavy and light chain

functional B cells never contain more than 1 heavy or light chain
-essential for specificity

expression of both alleles would render the B cell multispecific

can have Mom light and Dad heavy or vice versa

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Pro-B cell

right after the stem cell

starts to secrete Rag and TdT enzymes which allow it to go from pro-B cell to pre-B cell

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rearrangements of a heavy chain?

1 - D region joins with J region (forms DJ) - a random
2 - V region joined to DJ ( no C region yet) - forms VDJ
3 - VDJ is transcribed
4 - pre-mRNA has L-D-V-J and C regions and is spliced

**C-mew and C-delta are the constant regions
-make IgM and IgD, respectively

5 - mRNA is translated in the cytoplasms and the leader is removed as protein transported into the ER
-heavy chain is assembled with light chain

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mechanism of DNA rearrangement?

flanking the V, J, and D exons are RSS sequences
-each RSS has a nonamer and heptamer separated by 12 or 23 base pairs (1 or 2 turns)

**recombination only occurs between a 1 turn or 2 turn signal

recombination is catalyzed b Rag1 and Rag2 (VDJ recombinase)

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RSS

recombination signal sequence

flank the V D and J exons during DNA rearrangements

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Rag-1 and Rag-2

apart of the VDJ recombinase enzyme

catalyze the recombination of DNA segments

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junctional diversity

at the junction of hairpin cleavage - have sticky ends

TdT catalyzes the random polymerization of nucleotides without the need for a template

have P-nucleotides added on sticky end
have N-nucleotides added in non-templated manner

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TdT

catalyzes addition of nucleotides to the sticky ends of broken gene during rearrangement

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P nucletides

added asymmetrically to the cleaved ends by TdT

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N nucleotides

added without a template by TdT

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pre-B receptor

complex of of the IgM without the surrogate light chains
-combined with the Ig-alpha and Ig-beta

**this is the first checkpoint - if heavy chain rearranged successfully

if not successful, cell dies by apoptosis (only 1 in 3 survive)

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what light chain is made first?

always KAPPA

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light chain rearrangement

V joins with J ( no D region in light chain)

otherwise, mechanism is the same as the heavy chain

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receptor editing

nonproductive light chain rearrangements can be rescued
-check for self recognition by bone marrow

if light chain is again not productive (up to 5 for kappa)
-depends on which kappa is chosen

if all kappa is unsuccessful, will go to lambda light chain

**only in the light chains

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immature B cell

has rearranged heavy and light chain successful

if all successful, will release a mature naive B cell

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alternative splicing

of mew and delta C regions

get both IgG and IgM on the surface of B cell

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components of the B cell receptor?

IgM heavy and light chain, Ig-alpha, and Ig-beta

checked by bone marrow stromal cells by presenting self (HLA)
-if strong interaction - negative selection
-if low affinity - positive selection

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combinatorial diversification

10'11 possible antibodies

not all gene segments are possible

pseudogene - accumulated mutations prevent encoding

several VDJ segments - no evolutionary pressure
-therefore they may be loss

during junctional diversity (N and P nucleotides)
-may add frameshifts, stop codons, and gobbledy gook

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junctional diversity

can triple the diversity of genetic sequence alone

diversity is generated in the hypervariable region

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secondary rearrangement diversity

is antigen specific

happens in the periphery

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SCID

mutations in Rag-1 and Rag-2

also by mutation in Il-7