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
2
Q
give some properties of antiviral interferons
A
activate NK cells
can be induced in response to dsRNA production
3
Q
what can infection of cells by retroviruses cause
A
syncytia
4
Q
name a cell that can be induced in response to dsRNA production
A
interferon
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
6
Q
what are some properties of human filoviruses
A
Are enveloped
Contain a polymerase in their viral particles
7
Q
name a human virus that is enveloped and contains a polymerase in its viral particles
A
human filovirus
8
Q
where was HIV1 probably first transmitted to humans
A
in Africa
9
Q
name a virus with a dimeric genome
A
HIV
10
Q
name broad process of activation of AB producing cells
A
clonal selection
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
12
Q
what determines clonal proliferation
A
antigen binding on B lymphocytes
13
Q
what is involved in the cell mediated response
A
T lymphocytes
14
Q
what is involved in the humoral response
A
B lymphocytes
15
Q
where does generation of diversity from hematopoietic stem cell occur
A
in primary lymphoid organs
16
Q
where does deletion of B cells occur
A
in primary lymphoid organs
17
Q
name the primary lymphoid organs
A
bone marrow
thymus
18
Q
name the secondary lymphoid organs
A
lymph nodes
spleen
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
20
Q
how are antibody producing cells activated
A
by clonal selection
21
Q
what is proliferation of activated cells followed by
A
differentiation into plasma cells, then memory cells
22
Q
what is life span of plasma cellls
A
4-5 days, 1-2 mnths
produce 2000ABs/second
23
Q
how many ABs do plasma cells produce
A
2000 oer second
24
Q
what is lifespan of memory cells
A
years to decades
25
how do memory cells differentiate back into plasma cells
following stimulation by same antigen
26
if memory cell is stimulated by same antigen, what happens to it
it will differentiate into plasma cell
27
which cells release cytokines
T cells
28
what do cytokines do
activate B cells
29
what is primary response
following exposure to antigen, theres slow rise in IgM followed by slow rise in IgG
30
following exposure to antigen, discuss IgM and IgG levels
following exposure to antigen theres a slow rise in IgM then slow rise in IgG
31
what is secondary response
following exposure to previously encountered antigen, theres a rapid rise in IgG and slow or no rise in IgM
32
discuss IgG and IgM levels in secondary response
rapid rise in IgG, slow or no response in IgM
33
discuss IgG and IgM levels in primary and secondary response
in primary: slow rise IgM followed by slow rise IgG
in secondary:
rapid rise IgG, slow or no response in IgM
34
name some granulocytes (polymorphoneuclear leukoctes)
```
mast cell precurosor
neutrophil
eosinophil
basophil
monocyte
```
35
outline negative selection in the bone marrow
happens when an immature B cell IgM binds to self - so is removed from the repertoire
36
what cells do activated B cells give rise to
plasma and memory cells
37
where does antibody secretion occur
in bone marrow and lymphoid tissue
38
outline structure of the BCR
membrane bound antibody
2 heavy 2 light chains
variable regions for antigen binding
39
what are the light chains of ABs called
kappa or lamda
40
what are the heavy chains of ABs called
theta gamma alpha delta or epsilon
41
which AB has greatest hinge region
IgA - bigger bidnding
42
which frament contains all antigen binding specificity
Fab
43
what is the Fab region
where antigen binding specificity is
44
what is the hinge region
open region - site of segmental flexibility
45
which section of AB is good for medical/therapeutic purposes
Fab region
| without Fc region theres less chance of AB being a physical limitation - can just use Fab region to get to tumour
46
how many different BCRs can be produced
milli
47
how is diversity of BCRs generated
by rearrangement of the BCR genes; somatic recombination
48
what is a use for somatic combination
rearrangement of BCR genes to generate diversity of different receptors
49
what is somatic recombination
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
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
somatic recombination
51
how many segments is the V domain of an Ig coded by?
| what are they
2 - V gene segment and J gene segment
52
what are light chains made up of
V and J
53
what segments are heavy chains made of
V D J
54
which sequence of AB/BCR is removed to make disulfide bonds
the L leader sequence
55
what happens to L leader sequence after translation
it is removed to make disulfide bonds
56
how many aas does V encode
variable gene segmentt encodes 95-101 aa
57
how many aas does J encode
joining segments
| up to 13 aa
58
what does D stand for
diversity segment
59
what is junctional diversity
process of recombination at the coding joint to generate diversity - where nucleotides are added or subtracted randomly
60
which AB segment is not present in light chains
D - diversity segment not present in light chains
61
what is the structure of the pre-B cell receptor
```
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
what is affinity maturation
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
what do all isotype switching response start as
IgM - cells can switch to making IgA,IgG, IgD etc
64
what do T cells contain that BCRs dont
cytoplasmic tail
65
what regions present in T cellls
```
V(ariable)
C(onstant)
H(inge)
transmembrane region
cytoplasmic tail
```
66
how many dimers in a T cell
heterodimeric alpha beta T cell receptor
67
what two main groups can T cells be divided into
```
CD4+ - helper - class 2 MHC
CD8+ = cytotoxic - MHC Class 1
```
68
what do CD4 and CD8 bind to
conserved regions of MHC molecules
69
what do MHC molecules do
present antigen to T cell
70
what class MHC does Cd4 recognise
class 2
71
what must T cells recognise
self MHC molecules and express CD4 (MHC2) or CD8 (MHC1)
72
discuss formation of variation among T cells
germline - beta chain rearranged and expressed, alpha chain rearranged and expressed
73
how is diversity increased for TCRs
by junctional diversity - like B cells
74
what processes confer diversity in BCRs
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
does somatic hypermutation occur in T cells
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
what is the structural diversity of T-cell receptors is mainly attributable to
combinatorial and junctional diversity generated
| during the process of gene rearrangement
77
which part of TCR contains highest diversity
central part, which contacts the bound peptide fragment of the ligand
78
which Ig isotypes lack hinge regions
Both IgM and
| IgE lack a hinge region but each contains an extra heavy-chain domain
79
why are IgM and IgE not like the other Ig isotypes
they lack a hinge region
| and contain an extra heavy domain
80
what are the 3 ways ABs participate in host defense
1. activate complement
2. opsonization
3. neutralisation
81
how do ABs deal with bacterial toxins
neutralisation
82
how do ABs deal with bacteria in extra cellular space
opsonization for ingestion
83
how d Igs deals with bacteria in plasma
complement activation
84
why does dneutralisation of bacterial toxins occur
because unbound toxin can react with cell receptors, but toxin:antibody cant
85
why does opsonixation occur
if antibodies coat it - it makes bacteria recognizable by phagocytosis
86
which Igs can form multimers
IgM and IgA
87
which MHC Class molecules are peptides from the cytosoml bound to
MHC1 - CD8
| think cytosol - cytotoxic
88
which MHC class molecules are peptides from vesicles bound to
MHC2 -Cd4
89
what are successive stages in the development of thymocytes marked by
changes in cell surface molecules
90
what surface changes to thymocytes undergo in T cell development
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
what can be used as markers for stages of T cell development
particular combinations of cell-surface proteins
92
which two distinct lineages of T cells are produced early in T cell development - which pop was major, which is minor
alpha:beta (major pop) and gamma:delta (minor pop)
93
what triggers an initial phase of differentiation along the Tcell lineage pathway followed by cell proliferation
interactions with the thymic stroma
94
what are double negative thymocytes
thymocytes/immature T cells which dont have CD4 or CD8 receptors
95
discuss flowchart of T cell development
double negative thymocyte -> beta chain rearranged -> alpha and beta chanin rearranged - double positive with CD4 and CD8
96
what different TCRs could be generated after development
1. unable to recognise MHC - useless
2. able to recognise MHC - useful
3. high affinity for MHC and self antigen = dangerous
97
what % of T cells produced in thymus die
95%
98
how do CD8+ cells kill
by releasing granzymes and perforin or by engagement of Fas on target cells by Fas ligand
99
what is T cell positive selection
double positive cells checked for their ability to recognise MHC
if no recognition - death by neglect
100
what happens to T cells that arent double positive
death by neglect - cant release signals
101
what is T cell negative selection
double positive/single positive cells with high affinity for MHC and self antigen are removed
102
what is role of Th1 cd4 cellsq
recognise complex of bacterial peptide with MHC Class2 and activate macrophage
direct and regulate other arms of the immune system
103
which T cell activates macrophages
helper T cells
| Cd4
104
what are CTLs
cytotoxic T lymphocytes
105
what is role of T cells
recognise viral antigens on MHC1 - directly kill target cells with viruses
106
what factors regulate T and B cell development
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
what is RAG
| which cells express it
developing T and b cells are the only cells to express RAG - recombinase activating gene
108
what IL do T and B cells require for development
interleukin 7
109
what cells do T and B cells require interaction with
thymus/bone marrow stromal cells
