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immuno med wk 2 > Anderson Lecture > Flashcards

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
Q

Each variable region on the light chain gene has two exons

A

one variable exon, one variable exon

26
Q

Lambda light chain genes

n =
constant region genes =

two exons associated with each gene region

A

n = 30
Cn = 4
Exon n = leader and variability exon

27
Q

kappa light chain genes

n =

constant region genes =

two exon associated with each gene =

A

n = 300
Cn = 1
exon n = one leader exon, one variable exon

joining region between V and C

28
Q

“three” events occur before the VJC light chain is produced

A

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
Q

how does junctional diversity work?

A

the deletion or addition of nucleotides from VDJ segments by exonucleases at time of recombination

30
Q

VDJ Recombinase

A

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
Q

recombination switch sequence

consists of three elements….

A

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
Q

how many bps between heptamer and noamer

A

12-23 bps

33
Q

TdT

A

terminal deoxyribonucleotidyl transferase

34
Q

what does the TdT do?

A

takes nucleotides that are not part of germline and adds them to sites of VDJ recombination

35
Q

what does the “junction” caused by TdT do specifically

A

it encodes the amino acids of CDR3

CDRs are short hypervariable regions of amino acids within the V regions

36
Q

CDR3

A

one of the most variable CDRs

37
Q

Isotype switching

what region constitutes the “isotype”

A

the Constant region

38
Q

Isotype (class) switching occurs by

A

“switch recombination” in which DNA is deleted

39
Q

what’s the big picture of isotype switching?

A

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
Q

Somatic hypermutation

A

only occurs in B cells: OCCURS WHEN MEMORY CELLS ARE RE-STIMULATED AND UNDERGO RAPID PROLIFERATION

41
Q

where does somatic hypermutation occur?

A

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
Q

what happens during somatic hypermutation?

A

point mutations occur in the V(L) H(L) chains that increase their affinity for the epitope = affinity maturation

43
Q

affinity maturation =

A

point mutations occur in the V(L) H(L) chains that increase their affinity for the epitope = affinity maturation

44
Q

how is somatic hypermutation “initiated” ?

A

cytosine bases are deaminated to uracil; repair mechanism convert back to cytosine but is error prone, introduces mutations

45
Q

what happens to the CDR’s dissociation constant from the primary to the second and third exposure?

A

it decreases

46
Q

what kind of genetic alteration do TCRs undergo?

A

somatic recombination

47
Q

the genes coding for MHC

A

human leukocyte antigens (HLA antigens in people)

48
Q

principle determinants for graft acceptance or rejection between individuals

A

MHC

49
Q

who can receive grafts without activating an immune response?

A

monozygotic twins, that’s it

50
Q

MHC can bind numerous epitopes, therefore they are called

A

degenerate

51
Q

MHC is 1) highly polymorphic or 2) not polymorphic

A

1) highly polymorphic

alleles are inherited from both parents and expressed equally

52
Q

where is the binding cleft

A

in the mature HLA cell surface protein

53
Q

MHC genes are on chromosome

A

6

54
Q

MHC alleles are

A

codominant

both alleles from parents are expressed

55
Q

ABC what?

A

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
Q

RQP what?

A

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
Q

Skin grafts 1-4

A

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
Q

HLA typing

for grafts, which HLA genes are focused on?

A

HLA-A, B, DR

these loci seem to predict whether graft will be rejected

59
Q

testing for tissue transplantation: what do they check for?

A

ABO blood type
HLA-A, B, DR
preformed Abs
crossmatching

60
Q

What is a haplotype used for?

A

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

immuno med wk 2 (27 decks)

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