Anderson Lecture Flashcards

1
Q

Light chains

A

each antibody has two identical light chains: kappa or lambda, but never both

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2
Q

Kappa chain genes are found on

A

chromosome 2

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3
Q

Lambda chain genes are found on

A

chromosome 22

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4
Q

Heavy chain are encoded by chromosome

A

14

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5
Q

Delta, Alpha, and Gamma all have ___ constant domains

A

3

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6
Q

M and E Abs each have ____ constant domains

A

4 domains

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7
Q

double negative T cells are found in the

A

subcapsular cortex region of the thymus

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8
Q

double positive T cells are found in the

A

cortex of the thymus

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9
Q

single positive T cells are found in the

A

medulla

T cells whose receptors bind self-MHC molecule lose expression of either CD4 or CD8

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10
Q

After clonal expansion, T cells interact with APCs and B cells simultaneously. What does this do for the B cell?

A

allows it to react immediately to free antigens and proliferate

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11
Q

how many gene recombination events are required to produce the Ig heavy chain?

what are they?

A

2

bringing D and J –> DJ

bringing DJ to V –> VDJ

note: intervening segments are deleted

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12
Q

how many gene recombination events occur to make the Ig light chain?

A

just one: bringing the V and J together

V+J = VJ = recombination

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13
Q

Promoter

A

the V gene promoter is brought closer to the enhancer between J and C regions

mRNA translation, L is removed as protein is transported into ER

Light chain/heavy chain assemble in ER

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14
Q

the light chain and the heavy chain assemble in the

A

ER

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15
Q

V segments consist of ______ # segments

A

30-35

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16
Q

J segments consist of _____# segments

A

5

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17
Q

C segment consists of ____# segments

A

1

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18
Q

what does DJ binding do

A

it brings the C segment in close proximity

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19
Q

what does VDJ binding do

A

it makes a transcript ready to be translated into an RNA

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20
Q

what happens during translation of VDJ?

A

the intervening segments between the VDJ and C are deleted

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21
Q

how are the VDJ actually attached/what order?

A

it’s actually DJVC

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22
Q

what happens to the light chain D region?

A

it doesnt have one

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23
Q

who is closer to the C segment in the light chain gene, V or J?

A

J

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24
Q

what gets made? in the light chain recombination?

A

VJC

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25
Each variable region on the light chain gene has two exons
one variable exon, one variable exon
26
Lambda light chain genes n = constant region genes = two exons associated with each gene region
n = 30 Cn = 4 Exon n = leader and variability exon
27
kappa light chain genes n = constant region genes = two exon associated with each gene =
n = 300 Cn = 1 exon n = one leader exon, one variable exon joining region between V and C
28
"three" events occur before the VJC light chain is produced
1) deletion of intervening DNA and bringing together of VJ genes 2) transcription into mRNA 3) deletion of mRNA separating VJ and C regions --> VJC RNA transcript
29
how does junctional diversity work?
the deletion or addition of nucleotides from VDJ segments by exonucleases at time of recombination
30
VDJ Recombinase
collection of enzyme, expressed in immature B and T lymphocytes recognizes DNA sequences that flank all antigen receptor VDJ gene segments brings elements closer together consists of recombinase activating gene 1 and 2 RAG-1 and RAG-2 exonucleases cut DNA at the ends of segments ligases repair the breaks
31
recombination switch sequence consists of three elements....
found next to every VDJ segment consists of a heptamer, noamer, spacer of 12/23 bp RAG-1 and 2 bind to 12 bp and 23 bp spacer and brings the VD and DJ segments together
32
how many bps between heptamer and noamer
12-23 bps
33
TdT
terminal deoxyribonucleotidyl transferase
34
what does the TdT do?
takes nucleotides that are not part of germline and adds them to sites of VDJ recombination
35
what does the "junction" caused by TdT do specifically
it encodes the amino acids of CDR3 CDRs are short hypervariable regions of amino acids within the V regions
36
CDR3
one of the most variable CDRs
37
Isotype switching what region constitutes the "isotype"
the Constant region
38
Isotype (class) switching occurs by
"switch recombination" in which DNA is deleted
39
what's the big picture of isotype switching?
IgM transcript is produced first. in response to T cell signaling, the G A M E D "switch regions" are pasted onto the VDJ segment
40
Somatic hypermutation
only occurs in B cells: OCCURS WHEN MEMORY CELLS ARE RE-STIMULATED AND UNDERGO RAPID PROLIFERATION
41
where does somatic hypermutation occur?
in the germinal centers of lymphoid follicles followed by selection of high affinity B cells who express high affinity for antigen displayed by follicular dendritic cells
42
what happens during somatic hypermutation?
point mutations occur in the V(L) H(L) chains that increase their affinity for the epitope = affinity maturation
43
affinity maturation =
point mutations occur in the V(L) H(L) chains that increase their affinity for the epitope = affinity maturation
44
how is somatic hypermutation "initiated" ?
cytosine bases are deaminated to uracil; repair mechanism convert back to cytosine but is error prone, introduces mutations
45
what happens to the CDR's dissociation constant from the primary to the second and third exposure?
it decreases
46
what kind of genetic alteration do TCRs undergo?
somatic recombination
47
the genes coding for MHC
human leukocyte antigens (HLA antigens in people)
48
principle determinants for graft acceptance or rejection between individuals
MHC
49
who can receive grafts without activating an immune response?
monozygotic twins, that's it
50
MHC can bind numerous epitopes, therefore they are called
degenerate
51
MHC is 1) highly polymorphic or 2) not polymorphic
1) highly polymorphic alleles are inherited from both parents and expressed equally
52
where is the binding cleft
in the mature HLA cell surface protein
53
MHC genes are on chromosome
6
54
MHC alleles are
codominant both alleles from parents are expressed
55
ABC what?
ABC class 1 genes; only the alpha chain is polymorphic i. difference between individuals occur in the alpha1 and alpha2 domains ii. alpha3 is invariant and binds to CD8
56
RQP what?
RQP class II genes; both alpha/beta chains are polymorphic differences between individuals occur in the alpha1/beta1 domains CD4 binds to beta2 CD4 T cells can only respond to class II MHC molecules
57
Skin grafts 1-4
autographs (autologous): grafts from one place on a person to another on the same person isographs (synergic): grafts between two identical people allogeneic: grafts between different people xenogeneic grafts: grafts between species
58
HLA typing for grafts, which HLA genes are focused on?
HLA-A, B, DR these loci seem to predict whether graft will be rejected
59
testing for tissue transplantation: what do they check for?
ABO blood type HLA-A, B, DR preformed Abs crossmatching
60
What is a haplotype used for?
a set of alleles of linked genes present on one parental chromosome set of genes that determine antigens but are closely linked and inherited as a unit you would compare the haploids of the donator to the patient