module 03 section 02 (innate immune system) Flashcards

(79 cards)

1
Q

what did Susumu Tonegawa discover?

A

he eludicated the mechanism for making millions of different antibody molecules with different specificities without requiring an unreasonably large number of genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

when do Igs ungergo “somatic recombination” ?

what part of the Ig does this refer to?

A

heavy and light chains undergo somatic recombination of genetic material during the early stages of B- and T-cell maturation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what does somatic recombination allow for?

A

a high degree of diversity among Igs and T-cell receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

in addition to somatic recombination, what contributes to the diversity of Igs?

A

the fact that each class of Ig has a separate pool of gene segments from which the final Ig in synthesized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the 4 classifications of genes contained in the light chains?

A
  • leader sequences
  • variable gene segments
  • joining gene segments
  • constant gene segments
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

light chains can be classified into two groups, what are they? and what are these groups based on?

A

kappa, lambda - based on small differences in polypeptide sequence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

the lambda light chain locus is found on what chromosome?

A

22

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

describe the lambda light chain

A

there are several J and C segments, each interacting with only its corresponding segment (e.g. J lambda1, 2, 3, or 4 and C lambda1, 2, 3 or 4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

the kappa light chain is found on what chromosome?

A

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

describe the kappa light chain

A

each Jk can join with the same Ck (as there is only one Ck)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

describe the process of kappa light chain rearragement (5 steps)

A

(1) DNA rearrangement -somatic recombination: V-J joining (regulated by RAG)
(2) transcription and rna processing (splicing)
(3) mulitple adeinin nucelotides (poly-A-tails) are added to polyadenylation sites at 3’ of Ck
- mRNA exists the nucelus to bind ribosomes in the rough ER - translation
(4) L sequence pulls growing polypeptide into lumen of ER and is then cleaved off
(5) processing and glycosylation of the protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

if there wass a mutation in the RAG genes (recombinase enzymes that act on the variable regions of Ig) would Igs be made? would B-cells be made?

A

niether would be made

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

the heavy chain locus is found on what chromosome?

A

14

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

describe formation of the heavy chain

A

one D segment joins with a J segment, then a V segment joins with the D-J segment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

describe the process of heavy chain rearrangement (6 steps)

A

(1) first rearrangement - somatic recombination: D-J joining (regulated by RAG)
(2) second rearrangement - somatic recombination: V-DJ joining (regulated by RAG)
(3) transcription and rna processing (splicing)
(4) mulitple adeinin nucelotides (poly-A-tails) are added to polyadenylation sites at 3’ of Cu (mu)
- mRNA exists the nucelus to bind ribosomes in the rough ER - translatio
(5) L sequence pulls growing polypeptide into lumen of ER and is then cleaved of
(6) processing and glycosylation of the protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

each unique heavy chain associates with a light chain to create a unique Ig, true or false?

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

the variable regions are the:

A

exons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

how many variable heavy chain regions have we idenitifed?

A

100-200

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how many diversity (D) heavy chain regions have we identified?

A

50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

how many joining heavy chain regions have we identified?

A

6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

recap: how many constant gene segments are there in the kappa light chain ?

A

1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

recap: what is unique about the J lambda 4 gene?

A

it is a pseudogene, or a non-functional gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

recap: what gives rise to antibody specificity (peritope)?

A

the V-DJ (heavy) and the V-J (light) regions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

how do we make different classes of antibodies with the same antigenic specificity?

A

class switch recombination - type of gene rearrangement where the constant gene regions in the Ig heavy chain switch from being one class to another (e.g. go from IgM to IgG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
where does class switch recombination occur?
btwn the switch sites which are located upstream of the CH regions
26
can switch rearrangement occur with IgD? why or why not?
no - has no switch site
27
with what Igs can IgM do switch rearrangement with?
IgM --> IgG, IgA | this way only - can't go from IgA to IgM
28
can switch rearrangement occur from IgM to IgE?
yes - but have to go from IgM to IgG then from IgG to IgE
29
how many possible heavy and light chain associations are there?
2.64 million
30
how many possible combinations of VJ rearrangements are there for k light chains?
200
31
how many possible combinations of VJ rearrangements are there for λ light chains?
100
32
how many heavy chain V segments are there?
51
33
how many heavy chain D segements are there?
27
34
how many J segments are there?
6
35
how many possible heavy chain V regions are there?
8262
36
recap: what primarily allows for Ig diversity?
gene rearrangement
37
what are recombination singal sequences?
conserved sequences of noncoding DNA that function as signals for the recombination process in heavy and light chain rearrangements
38
where are recombination singal sequences found in terms of where recombination takes place?
directly adjacent to the point at which recombination takes place
39
recombination singal sequences are recognized by ____ during what process?
RAG1 and RAG2 during VDJ recombination
40
what is RAG1? what is its role?
- enzyme encoded by recombination activating gene 1 | - plays important role in the rearrangement and recombination of antibody and t-cell receptor molecules
41
what is RAG2? what is its role?
- enzyme encoded by recombination activating gene 2 | - plays important role in the rearrangement and recombination of antibody and t-cell receptor molecules
42
where are recombination singal sequences found on the V segment?
3' end
43
where are recombination singal sequences found on the J segment?
5' end
44
where are recombination singal sequences found on the D segment?
both 3' and 5' ends
45
what do all recombination singal sequences contain? (2)
- a conserved palindromic heptamer - a conserved AT-rish nonamer sequence - the two are separated by either 12 or 23 non-conserved bps (if there's 1 or 2 turns of the DNA helix)
46
what does the one-turn/two-turn joining rule state?
that signal sequences with a one turn spacer can only join with a sequence that has a two turn spacer (and vice versa)
47
what happens when a one-turn and a two-turn sequence join?
the resulting gene sequence forms a loop, then the RAG enzyme cuts the excess gene segment
48
are the 12/23 bp spacers conserved when one-turn and two-turn sequences join?
no
49
are the palindromic and AT-rich signal sequences conserved when one-turn and two-turn sequences join?
yes - they form circular dna that gets degraded
50
what is the result of the looping that occurs due to the palindromic and AT-rich sequences?
the merging of VJ segments
51
rearrangement can be productive or nonproductive, true or false? why?
true
52
the amino acid sequence variation generated by gene rearrangement in the coding joint has been shown to fall within:
the third hypervariable region (CRD3) in immunoglobulin heavy and light chain DNA
53
CRD3 plays a key role in:
the recognition of unique epitopes
54
what is productive rearrangement?
the joining of VDJ segments in phase to produce VJ or a VDJ unit that can be translated in its entirety
55
what does one productive rearrangement mean?
one allele is enough to make the immunoglobulin
56
what is nonproductive rearrangement?
rearrangement in which gene segments are joined out of phase so that the triplet-reading frame for translation is not preserved (i.e. there is a stop codon)
57
what happens if there is a nonproductive rearrangement?
the immunoglobulin chain is not made
58
the site where polyadenylation occurs directs:
whether the antibody produced will be membrane bound or secreted
59
the constant regions of IgM and IgD are processed at the same time, true or false? why?
true - they are the first immunoglobulins produced
60
where do immature developing B-cells favour polyadenylation? what is the result?
at poly-A site 2 and 4 to produce membrane bound antibodies
61
where do plasma cells favour polyadenylation? what is the result?
at poly-A site 1 and 3 to produce secreted antibodies
62
describe the process of class switching
ds dna breaks are generated at the switch sites, removing unwanted portions of the CH and the remaining segments are re-joined by non-homologous end-joining to produce a different antibody isotype
63
does antigen specificity remain the same following class switching? why or why not?
yes - its dictated by the VH region which stays the same
64
what does the CH change (due to class switching) modify in terms of Ig function?
the effector molecules the antibody can interact with
65
what are the means of Ig diversity that we covered?
(1) junctional flexibility (VDJ) (2) combinatorial addition of light/heavy chains (3) nucelotide addition (P-region/N-region) (4) somatic hypermutation
66
where is the thrid hypervariable loop of Igs located?
at the joint btwn the V and J gene segment
67
in the heavy chain, CRD3 is partially encoded by the:
D gene
68
in both heavy and ligth chains, the diversity of CRD3 is significantly increased by:
the addition or deletion of nucleotides
69
when does nucleotide addition occur?
during the rearrangement of gene segments in the initial development of B-cells
70
describe how the addition of N-nucleotides adds diversity to the antigen binding site
- these are nontemplate-encoded | - these are added by TdT to single stranded ends of coding dna after hairpin cleavage
71
describe how the addition of P-nucleotides adds diversity to the antigen binding site
- these make up palindromic sequences | - these are added to the ends of gene segments (in the antigen binding site)
72
are somatic mutations random?
yes
73
where do somatic mutations occur?
in germinal centers where b-cells proliferate ONLY
74
what do somatic mutations target?
rearranged V regions (CRDs) located within the DNA requence influencing the VJ/VDJ rearrangement process
75
why are Ig somatic mutations reffered to as somatic hypermutations?
bc they have a frequency 100,000 times higher than the spontaneous rate in other genes
76
what are 2 processes that somatic mutations are associated with?
(1) class switching | (2) affinity maturation
77
what triggers class switching?
antigen stimulation
78
what is affinity maturation?
increase in the average affinity of an antibody for an antigen during the course of an immune response or in subsequent exposures to an antigen (resulting in the lock and key fit)
79
when does combinatorial diversity manifest?
when 2 separate units of genetic information combine