Lectures 19, 20, 21: Antigen Recognition by Lymphocytes Flashcards

1
Q

The BCR is compreised of ___(#) polypeptide chains, what are these chains?

A

4; 2 identical light chains and 2 identical heavy chains

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2
Q

the chains of the BCR are connected by ____ bonds

A

disulphide

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3
Q

what are the 2 types of light chains for the BCR?

A

lambda and kappa

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4
Q

light chains have ___(#) variable regions and ___(#) constant regions

A

1 and 1

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5
Q

heavy chains of BCR have __(#) variable regions and ___(#) constant regions

A

1; 3-4

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6
Q

there are multiple types of BCR heavy chains and they are defined by their ____ regions

A

constant

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7
Q

The TCR is made of ___(#) polypeptide chains which are linked by ____ bonds

A

2; disulphide

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8
Q

what are the 2 types of TCR?

A
  1. alpha/beta heterodimer

2. gamma/delta heterodimer

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9
Q

how many variable and constant regions does each TCR polypeptide have

A

1 constant and 1 variable region each

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10
Q

what are the 2 important fundamental differences between TCR and BCR?

A
  1. T cells do not secrete TCR while B cells do secrete immunoglobulin
  2. TCR is not specific for native or intact antigen, instead, antigen must be presented by self MHC
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11
Q

what are the receptor associated molecules for BCR?

A

Ig-alpha and Ig-beta

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12
Q

what is the receptor associated molecule of TCR

A

CD3

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13
Q

in an antibody, which terminus is the variable region and which is the constant region?

A

variable: amino
Constant: carboxyl

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14
Q

what are the 2 proposed models of antibody diversity?

A
  1. Germ-line theory

2. Somatic-variation theory

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15
Q

explain the germ-line theory

A

proposed there was a different gene for each immunoglobulin

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16
Q

explain the somatic variation theory of antibody diversity

A

proposed that the genome has few genes but that recombinations or mutations result in diversity

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17
Q

the same CH of CL region can be connected to millions of different ___ or ___ regions

A

VH or VL

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18
Q

the same VH region can be connected to different ___ regions

A

CH

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19
Q

in 1976, Tonegawa and Hozumi found direct evidence that separate genes encode the ___ and ___ regions of immunoglobulins

A

V and C

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20
Q

there are multiple ___ for each segment type (V,D,J) in the germ-line genome

A

gene segments

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21
Q

what is the only immunoglobulin to contain D regions?

A

IgH

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22
Q

what is a signal peptide?

A

sometimes called a signal sequence or leading sequence or leader peptide; a short peptide at the N-terminus of most new proteins that are destined for the secretory pathway

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23
Q

signal peptides are usually ___ AA long

A

5-30

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24
Q

t/f multiple gene segments recombine to form the final V region and this contributes to the diversity of the final antigen binding site

A

t

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25
Q

does the final assembled VJ or VDJ region recombine with the constant region exons?

A

no

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26
Q

all heavy region constant domain exons are on ____ (different/the same) chromosomes downstream of the ____ region gene segments

A

the same; V,D &J

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27
Q

what flags the site for recombinations?

A

specific sequence motifs

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28
Q

what are RSS (recombination signal sequences)

A

sequences that flank teh coding regions of the gene segments

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29
Q

in the variable regions, there are __(#) different RSS’s

A

2

30
Q

in the variable region, the RSSs have _____ heptamers and nonamers spaced by variable sequences of ____ to ___ (#) base pairs length

A

conserved palindromic; 12-23

31
Q

what is the V(D)J recombinase?

A

a multimolecular complex that includes lymphocyte-specific recombination activation gene products (RAG1 and RAG2)

32
Q

RAG1/2 and HMGB1/2 bind to the ____ and catalyse synapse formation between __ and __ gene segments

A

RSS; V & J

33
Q

RAG binding to the RSS lead to a ____ coding end

A

hairpin

34
Q

what are the 5 main steps of variable region recombination?

A
  1. RAG binds RSS, leading to hairpin coding end which gets cleaved
  2. P nucleotide additions
  3. Exonuclease trimming
  4. N nucelotide additions
  5. ligation of the DNA (coding & signal joints)
35
Q

what 5 mechanisms contribute to the generation of antibody diversity in variable region recombination?

A
  1. multiple gene segments (combinations)
  2. palindromic (P) nucleotide additions
  3. exonuclease trimming
  4. non-templated (N) nucleotide addition
  5. combinatorial diversity (two chains combining into one antigen binding site)
36
Q

particular regions in the V regions, called ____ directly contact the antigen

A

complementarity dertermining regions (CDR)

37
Q

CDR3 includes the site of the ___ gene segment recombinations

A

V(D)J

38
Q

after binding antigen, the V region CDR* can undergo mutations at a rate higher than typical in the genome, called _____

A

somatic hypermutation

39
Q

can somatic hypermutation contribute to diversity of the variable region?

A

yes, but in a subtle way

40
Q

by the end of variable region recombinations, the average affinity of antigen-specific BCRs and antibodies formed at the end of an immune response is much ____(higher/lower) than at the beginning

A

higher

41
Q

the net increase in Ig affinity among a population of B cells is called ____

A

affinity selection

42
Q

RNA splicing and polyadenylation signals guide the final mRNA of the ___ and ____ chain products

A

mu (IgM) and delta (IgD)

43
Q

the simultaneous expression of IgM and IgD on B cells is due to ____

A

alternative splicing of the mu or delta constant region exons

44
Q

what is class switch recombination?

A

AKA isotype class switching: chaning the constant region segments

45
Q

is the mechanism of class switch recombination the same as the mechanism behind variable region gene segment recombination?

A

no

46
Q

class switch recombination uses ___ regions and ___

A

switch; activation induced cytodine deaminase (AID)

47
Q

what are switch regions that are used in CSR?

A

they are highly repetitive DNA stretches 5’ of the constant domain exons

48
Q

what isotype(s) is made in response to IL-4?

A

IgG1 and IgE

49
Q

what isotype(s) are produced in response to TGF beta?

A

IgA and IgG2b

50
Q

what isotypes are produced in response to IL-5?

A

IgA

51
Q

what isotypes are made in response to IFN-gamma?

A

IgG3 and IgG2a

52
Q

is cytokine alone enough to promote CSR?

A

no, the B cell must also receive signal through CD40 or TLRs

53
Q

the gene segments of the T cell antigen receptor are fundamentally similar with some exceptions

A

t

54
Q

in the T cell receptor, there are multiple gene segments for each ____ region

A

V(D)J

55
Q

one difference in TCR from BCR is that the RSS of the TCR are arranged in a manner that permits multiple __ region use

A

D

56
Q

the TCR having its RSSs arranged in a way that permits multiple D region use is called ___

A

alternative joining of D segments

57
Q

what are S switch regions?

A

long stretches of G/C rich DNA with internal repeats, each switch region exon has unique repeats

58
Q

on B cells, are the variable regions of the light chains the same as the variable regions of the constant regions?

A

no

59
Q

t/f each AA loop is usually an exon

A

t

60
Q

would you ever see a kappa and lambda light chain on the same B cell receptor?

A

no (would always be two lambda or two kappa)

61
Q

in what step is it decided if the antibody will be secreted?

A

during alternative splicing

62
Q

if an antibody has a membrane spanning unit, what is its fate? What if it does not have this?

A

membrane bound = will remain on the surface of B cell; if not, it will be secreted

63
Q

do T cells secrete their receptors?

A

no

64
Q

do TCR have alternative splicing?

A

no

65
Q

light chain and heavy chains only rearrange in __ cells

A

B

66
Q

every kappa chain your B cells make will have the same ________ region

A

constant

67
Q

it is critical that recombinations occur in a way that preserves the ____ to make a V region

A

open reading frame

68
Q

if recombinations do not preserve an open reading frame, what happens to the B cell?

A

undergoes apoptosis

69
Q

in the heavy chain of B cells, why do the D regions have RSS on both sides?

A

bc they need to rearrange with both J and V at up and downstream

70
Q

can D chains recombine with each other?

A

no

71
Q

recombination can only occur between RSSs of ____(the same/different) lengths

A

different

72
Q

what is a palindrome?

A

read the same backwards and forwards