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MSS-IHL Final Exam > Diversity vs. Specificity: Immunoglobulins > Flashcards

Diversity vs. Specificity: Immunoglobulins Flashcards

0
Q

immunoglobulin structure

A

two identical heavy and two identical light chains

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1
Q

immunoglobulin

A

aka antibody

can be membrane bound or secreted

all antibodies made by a single cell and have specificity

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2
Q

IgM

A

surface bound antibody

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3
Q

Immunoglobulin superfamily

A

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

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4
Q

clonal selection

A

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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5
Q

primary immunoglobulin rearrangement

A

multiple germ line genes
-combinatorial diversification

junctional diversity
-addition of nucleotides during process of joining

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6
Q

secondary immunoglobulin rearrangement

A

somatic hypermutation

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

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7
Q

somatic hypermutation

A

happens during the immune response

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8
Q

IL-3

A

secreted by T cells

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9
Q

IL-7

A

necessary for commitment to lymphoid lineages

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10
Q

location of heavy chain

A

chromosome 14

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11
Q

two different light chains?

A

kappa and lambda

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12
Q

3’ end of gene?

A

C (constant regions)

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13
Q

5’ end of gene

A

V (variable regions)

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14
Q

what contains D regions?

A

Ig heavy chain and TCR beta chain

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15
Q

how many V regions in heavy chain

A

about 100 V regions

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16
Q

different C regions of heavy chain determine what?

A

determine the isotype of the Ig

17
Q

what genes in the heavy chain?

A

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

18
Q

what is in the kappa light chain?

A

only one C region

V regions have a leader exon and a V exon

several J regions between the V and C regions

19
Q

lambda light chain

A

4 C regions (with interspersed J regions)

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

20
Q

allelic exclusion

A

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

21
Q

Pro-B cell

A

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

22
Q

rearrangements of a heavy chain?

A

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

23
Q

mechanism of DNA rearrangement?

A

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)

24
Q

RSS

A

recombination signal sequence

flank the V D and J exons during DNA rearrangements

25
Q

Rag-1 and Rag-2

A

apart of the VDJ recombinase enzyme

catalyze the recombination of DNA segments

26
Q

junctional diversity

A

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

27
Q

TdT

A

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

28
Q

P nucletides

A

added asymmetrically to the cleaved ends by TdT

29
Q

N nucleotides

A

added without a template by TdT

30
Q

pre-B receptor

A

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)

31
Q

what light chain is made first?

A

always KAPPA

32
Q

light chain rearrangement

A

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

otherwise, mechanism is the same as the heavy chain

33
Q

receptor editing

A

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

34
Q

immature B cell

A

has rearranged heavy and light chain successful

if all successful, will release a mature naive B cell

35
Q

alternative splicing

A

of mew and delta C regions

get both IgG and IgM on the surface of B cell

36
Q

components of the B cell receptor?

A

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
37
Q

combinatorial diversification

A

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

38
Q

junctional diversity

A

can triple the diversity of genetic sequence alone

diversity is generated in the hypervariable region

39
Q

secondary rearrangement diversity

A

is antigen specific

happens in the periphery

40
Q

SCID

A

mutations in Rag-1 and Rag-2

also by mutation in Il-7

MSS-IHL Final Exam (15 decks)

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