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HELENP CBG VIROLOGY AND IMMUNITY > CBG Lecture 27: T and B cell development > Flashcards

CBG Lecture 27: T and B cell development Flashcards

1
Q

Which one or more of the following statements are true of the majority of RNA viruses?

A

replicate in the cytoplasm

have ss genomes

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2
Q

give some properties of antiviral interferons

A

activate NK cells

can be induced in response to dsRNA production

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3
Q

what can infection of cells by retroviruses cause

A

syncytia

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4
Q

name a cell that can be induced in response to dsRNA production

A

interferon

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5
Q

give some properties of NK cells

A

They play a role in antibody-dependent cell-mediated cytotoxicity
They can directly kill virus infected cells
They are part of the innate immune response

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6
Q

what are some properties of human filoviruses

A

Are enveloped

Contain a polymerase in their viral particles

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7
Q

name a human virus that is enveloped and contains a polymerase in its viral particles

A

human filovirus

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8
Q

where was HIV1 probably first transmitted to humans

A

in Africa

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9
Q

name a virus with a dimeric genome

A

HIV

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10
Q

name broad process of activation of AB producing cells

A

clonal selection

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11
Q

outline process of clonal selection

A

B lymphocytes recognise intact pathogenic microorgs and toxins
B lymphocytes possess antigen specific receptors
binding of specific antigen results in proliferation of clonal popn of cells
antigen determines clonal proliferation

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12
Q

what determines clonal proliferation

A

antigen binding on B lymphocytes

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13
Q

what is involved in the cell mediated response

A

T lymphocytes

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14
Q

what is involved in the humoral response

A

B lymphocytes

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15
Q

where does generation of diversity from hematopoietic stem cell occur

A

in primary lymphoid organs

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16
Q

where does deletion of B cells occur

A

in primary lymphoid organs

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17
Q

name the primary lymphoid organs

A

bone marrow

thymus

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18
Q

name the secondary lymphoid organs

A

lymph nodes

spleen

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19
Q

what are the postulates of the clonal selection hypothesis

A

each lymphocytes has a single specific unique receptor
lymphocyte activated if the interaction between a foreign molecule and lymphocyte receptor bind with high affinity
after activation, the differentiated effector cells derived form an activated lymphocyte bear exact specificity of parent cxell
lymphocytes bearing “self” receptors will be deleted early in lymphoid cell

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20
Q

how are antibody producing cells activated

A

by clonal selection

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21
Q

what is proliferation of activated cells followed by

A

differentiation into plasma cells, then memory cells

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22
Q

what is life span of plasma cellls

A

4-5 days, 1-2 mnths

produce 2000ABs/second

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23
Q

how many ABs do plasma cells produce

A

2000 oer second

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24
Q

what is lifespan of memory cells

A

years to decades

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25
Q

how do memory cells differentiate back into plasma cells

A

following stimulation by same antigen

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26
Q

if memory cell is stimulated by same antigen, what happens to it

A

it will differentiate into plasma cell

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27
Q

which cells release cytokines

A

T cells

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28
Q

what do cytokines do

A

activate B cells

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29
Q

what is primary response

A

following exposure to antigen, theres slow rise in IgM followed by slow rise in IgG

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30
Q

following exposure to antigen, discuss IgM and IgG levels

A

following exposure to antigen theres a slow rise in IgM then slow rise in IgG

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31
Q

what is secondary response

A

following exposure to previously encountered antigen, theres a rapid rise in IgG and slow or no rise in IgM

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32
Q

discuss IgG and IgM levels in secondary response

A

rapid rise in IgG, slow or no response in IgM

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33
Q

discuss IgG and IgM levels in primary and secondary response

A

in primary: slow rise IgM followed by slow rise IgG
in secondary:
rapid rise IgG, slow or no response in IgM

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34
Q

name some granulocytes (polymorphoneuclear leukoctes)

A 
mast cell precurosor
neutrophil
eosinophil
basophil
monocyte
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35
Q

outline negative selection in the bone marrow

A

happens when an immature B cell IgM binds to self - so is removed from the repertoire

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36
Q

what cells do activated B cells give rise to

A

plasma and memory cells

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37
Q

where does antibody secretion occur

A

in bone marrow and lymphoid tissue

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38
Q

outline structure of the BCR

A

membrane bound antibody
2 heavy 2 light chains
variable regions for antigen binding

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39
Q

what are the light chains of ABs called

A

kappa or lamda

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40
Q

what are the heavy chains of ABs called

A

theta gamma alpha delta or epsilon

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41
Q

which AB has greatest hinge region

A

IgA - bigger bidnding

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42
Q

which frament contains all antigen binding specificity

A

Fab

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43
Q

what is the Fab region

A

where antigen binding specificity is

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44
Q

what is the hinge region

A

open region - site of segmental flexibility

45
Q

which section of AB is good for medical/therapeutic purposes

A

Fab region

without Fc region theres less chance of AB being a physical limitation - can just use Fab region to get to tumour

46
Q

how many different BCRs can be produced

A

milli

47
Q

how is diversity of BCRs generated

A

by rearrangement of the BCR genes; somatic recombination

48
Q

what is a use for somatic combination

A

rearrangement of BCR genes to generate diversity of different receptors

49
Q

what is somatic recombination

A

bits DNA with highly specific regions moved around by enxymes: unique combination of segments become joined and chains pair to give unique receptor
segments of genomic DNA within the immunoglobulin genes are rearranged in
cells of the B-lymphocyte lineage, but not in other cells.

50
Q

WHAT IS the term for segments of genomic DNA within the immunoglobin genes getting rearranged in cells of B lymphocyte lineage but not in other cells

A

somatic recombination

51
Q

how many segments is the V domain of an Ig coded by?

what are they

A

2 - V gene segment and J gene segment

52
Q

what are light chains made up of

A

V and J

53
Q

what segments are heavy chains made of

A

V D J

54
Q

which sequence of AB/BCR is removed to make disulfide bonds

A

the L leader sequence

55
Q

what happens to L leader sequence after translation

A

it is removed to make disulfide bonds

56
Q

how many aas does V encode

A

variable gene segmentt encodes 95-101 aa

57
Q

how many aas does J encode

A

joining segments

up to 13 aa

58
Q

what does D stand for

A

diversity segment

59
Q

what is junctional diversity

A

process of recombination at the coding joint to generate diversity - where nucleotides are added or subtracted randomly

60
Q

which AB segment is not present in light chains

A

D - diversity segment not present in light chains

61
Q

what is the structure of the pre-B cell receptor

A 
heavy chain rearranged first
expressed on the surfface as a preBcR
shuts down heavy chain rearrangement
then light chain rearranged
BCR checked for autoreactivity
if no reactivity it can exit
62
Q

what is affinity maturation

A

when Tfh cell-activated B cells produce antibodies with increased affinity for antigen during IS. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response can elicit antibodies with greater affinity than in a primary response. Affinity maturation primarily occurs on BCRs result of somatic hypermutation (SHM) and selection by Tfh cells

63
Q

what do all isotype switching response start as

A

IgM - cells can switch to making IgA,IgG, IgD etc

64
Q

what do T cells contain that BCRs dont

A

cytoplasmic tail

65
Q

what regions present in T cellls

A 
V(ariable)
C(onstant)
H(inge)
transmembrane region
cytoplasmic tail
66
Q

how many dimers in a T cell

A

heterodimeric alpha beta T cell receptor

67
Q

what two main groups can T cells be divided into

A 
CD4+ - helper - class 2 MHC
CD8+ = cytotoxic - MHC Class 1
68
Q

what do CD4 and CD8 bind to

A

conserved regions of MHC molecules

69
Q

what do MHC molecules do

A

present antigen to T cell

70
Q

what class MHC does Cd4 recognise

A

class 2

71
Q

what must T cells recognise

A

self MHC molecules and express CD4 (MHC2) or CD8 (MHC1)

72
Q

discuss formation of variation among T cells

A

germline - beta chain rearranged and expressed, alpha chain rearranged and expressed

73
Q

how is diversity increased for TCRs

A

by junctional diversity - like B cells

74
Q

what processes confer diversity in BCRs

A

junctional diversity -add/delete nucleotides
combinatorial diversity - of V D J segments
somatic recombination because V regions are encoded by separate gene segments, which are brought
togetherto make a complete V-region gene
somatic hypermutation - after an immunoglobulin has been expressed, the coding sequences for
its V regions are modified by somatic hypermutation upon stimulation of the B cell by antigen

75
Q

does somatic hypermutation occur in T cells

A

NO - variability of the CDR1 and CDR2 of T cells regions is limited to
that of the germline V gene segments. All the diversity in T-cell receptors is generated during rearrangement and is
consequently focused on the CDR3 regions.

76
Q

what is the structural diversity of T-cell receptors is mainly attributable to

A

combinatorial and junctional diversity generated

during the process of gene rearrangement

77
Q

which part of TCR contains highest diversity

A

central part, which contacts the bound peptide fragment of the ligand

78
Q

which Ig isotypes lack hinge regions

A

Both IgM and

IgE lack a hinge region but each contains an extra heavy-chain domain

79
Q

why are IgM and IgE not like the other Ig isotypes

A

they lack a hinge region

and contain an extra heavy domain

80
Q

what are the 3 ways ABs participate in host defense

A
  1. activate complement
  2. opsonization
  3. neutralisation
81
Q

how do ABs deal with bacterial toxins

A

neutralisation

82
Q

how do ABs deal with bacteria in extra cellular space

A

opsonization for ingestion

83
Q

how d Igs deals with bacteria in plasma

A

complement activation

84
Q

why does dneutralisation of bacterial toxins occur

A

because unbound toxin can react with cell receptors, but toxin:antibody cant

85
Q

why does opsonixation occur

A

if antibodies coat it - it makes bacteria recognizable by phagocytosis

86
Q

which Igs can form multimers

A

IgM and IgA

87
Q

which MHC Class molecules are peptides from the cytosoml bound to

A

MHC1 - CD8

think cytosol - cytotoxic

88
Q

which MHC class molecules are peptides from vesicles bound to

A

MHC2 -Cd4

89
Q

what are successive stages in the development of thymocytes marked by

A

changes in cell surface molecules

90
Q

what surface changes to thymocytes undergo in T cell development

A

expression of cell surface proteins like CD3 complex and the coreceptor proteins Cd4 and CD8 - these surface changes reflect the state of functional maturation of the cell

91
Q

what can be used as markers for stages of T cell development

A

particular combinations of cell-surface proteins

92
Q

which two distinct lineages of T cells are produced early in T cell development - which pop was major, which is minor

A

alpha:beta (major pop) and gamma:delta (minor pop)

93
Q

what triggers an initial phase of differentiation along the Tcell lineage pathway followed by cell proliferation

A

interactions with the thymic stroma

94
Q

what are double negative thymocytes

A

thymocytes/immature T cells which dont have CD4 or CD8 receptors

95
Q

discuss flowchart of T cell development

A

double negative thymocyte -> beta chain rearranged -> alpha and beta chanin rearranged - double positive with CD4 and CD8

96
Q

what different TCRs could be generated after development

A
  1. unable to recognise MHC - useless
  2. able to recognise MHC - useful
  3. high affinity for MHC and self antigen = dangerous
97
Q

what % of T cells produced in thymus die

A

95%

98
Q

how do CD8+ cells kill

A

by releasing granzymes and perforin or by engagement of Fas on target cells by Fas ligand

99
Q

what is T cell positive selection

A

double positive cells checked for their ability to recognise MHC
if no recognition - death by neglect

100
Q

what happens to T cells that arent double positive

A

death by neglect - cant release signals

101
Q

what is T cell negative selection

A

double positive/single positive cells with high affinity for MHC and self antigen are removed

102
Q

what is role of Th1 cd4 cellsq

A

recognise complex of bacterial peptide with MHC Class2 and activate macrophage
direct and regulate other arms of the immune system

103
Q

which T cell activates macrophages

A

helper T cells

Cd4

104
Q

what are CTLs

A

cytotoxic T lymphocytes

105
Q

what is role of T cells

A

recognise viral antigens on MHC1 - directly kill target cells with viruses

106
Q

what factors regulate T and B cell development

A

both require interaction with stromal cell in bone marrow or thymus
both require IL-7 to sustain development
both express RAG - recombinase activation gene to joins segments
developing T and B cells are the only cells to express RAG

107
Q

what is RAG

which cells express it

A

developing T and b cells are the only cells to express RAG - recombinase activating gene

108
Q

what IL do T and B cells require for development

A

interleukin 7

109
Q

what cells do T and B cells require interaction with

A

thymus/bone marrow stromal cells

HELENP CBG VIROLOGY AND IMMUNITY (8 decks)

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