CHAPTER 5.2: STAGES OF B AND T CELL DIFFERENTIATION Flashcards
(162 cards)
1
Q
Proteins that appear on cell surfaces can be used as markers to differentiate
A
T cells and B cells
2
Q
Proteins can also be used to distinguish the developmental stages of the two types of cells according to when these proteins appear
A
3
Q
• It acts as a reference in standardizing names of membrane proteins found on all human white blood cells
A
CLUSTER OF DIFFERENTIATION
4
Q
• Give rise to a lymphoid myeloid progenitor
A
MULTIPOTENTIAL PROGENITOR STEM CELL (MMP)
5
Q
LYMPHOID MYELOID PROGENITOR
• further differentiate to a (?)
A
common myeloid progenitor (MPP) and common lymphoid progenitor (CLP)
6
Q
give rise to erythrocytes, granulocytes (eosinophil, basophil, neutrophil), monocytes and megakaryocyte (platelets)
A
Common Myeloid Progenitor
7
Q
• give rise to T cells, B cells, Natural killer cells and dendritic cell
A
Common Lymphoid Progenitor
8
Q
will depend on the exposure to the different cytokines
A
Common Lymphoid Progenitor
9
Q
B Cell Differentiation
A
- Pro-B cell
- Pre-B cell
- Immature B cell
- Mature B cell
- Activated B cell
- Plasma Cell
10
Q
T Cell Differentiation
A
- Double negative stage
- Double positive stage
- Mature T cell
- Antigen activation
11
Q
STAGES OF B CELL DIFFERENTIATION
A
- PRO-B CELL
- PRE-B CELL
- IMMATURE B CELL
12
Q
- PRO-B CELL
During this maturation process, the first step is the (?) (most important process in pro B cell) that code for the heavy and light chains of an antibody molecule.
A
rearrangement of genes
13
Q
- PRO-B CELL
The end result is a (?) programmed to produce a unique antibody molecule, which consists of (?)
A
B lymphocyte
two identical light chains and two identical heavy chains
14
Q
Does not require any antigen in order to differentiate or to mature into a next stage
A
Antigen Independent Phase
15
Q
Several transcriptions, or growth, factors are necessary to differentiate common lymphoid precursors to produce pro-B cells
A
Important Growth / Transcription factors for differentiation
16
Q
E2A, Early B-cell factor (EBF), Paired box protein (PAX) and Interleukin-7
A
Important Growth / Transcription factors for differentiation
17
Q
CD19, CD45R, CD43, CD24 and c-Kit
A
Distinctive Markers
18
Q
terminal deoxyribonucleotide transferase (TdT) -important in antibody construction
A
Intracellular Proteins
19
Q
recombination-activating genes (RAG-1 and RAG-2) codes for antibody production
A
Intracellular Proteins
20
Q
Note: rearrangement of (?) is the most important process in pro B cell
A
heavy chains
21
Q
Begins at the synthesis of the heavy chain part of antibody
A
- PRE-B CELL
22
Q
The first heavy chains synthesized are the μ chains, which belong to the class of immunoglobulins called IgM (monomer in pre-B cell but the circulating IgM is pentamer).
A
PRE-B CELL
23
Q
• CD43, c-Kit and TdT
A
Markers and proteins lost during process
24
Q
u chain, surrogate light chain and 2 very short polypeptide chains that are non-covalently associated with each other
A
Surface Receptors
25
Adhere to the bone marrow stromal cell and transmit signal to prevent rearrangement of any other heavy chain
Pre-B cell receptor
26
Stimulates burst of clonal expansion (continuous production)
Pre-B cell receptor
27
Note: rearrangement of (?) is the most important process in pre-B cell
light chains
28
IMMATURE B CELL
Distinguishing characteristic
Presence of complete IgM molecule in the cell surface
29
This indicates that rearrangement of the genetic sequence coding for light chains on either chromosome 2 or 22 has taken place by this time.
IMMATURE B CELL
30
Completion of light chain rearrangement commits a cell to produce an antibody molecule with specificity for a particular antigen or group of related antigens.
IMMATURE B CELL
31
acts as a receptor for a breakdown product of the complement component C3, known as C3d
32
This enhances the likelihood of contact between B cells and antigen, because antigen frequently becomes coated with complement fragments during the immune response
CD21
33
Important for interaction of B cells with T cells.
CD40 and MHC Class II molecule
34
2 Destinations
• Programmed cell death (apoptosis)
• The remaining 10% leave the bone marrow and seed the lymphoid organs
35
There is evidence that self-antigens can give a negative signal to immature B cells resulting in arrested maturation and cell death
36
Immature B cells that tightly bind self-antigens through cross-linking of surface IgM molecules receive a signal to halt development, and they are eliminated or inactivated
Programmed cell death (apoptosis)
37
90% of B cells die in this manner without leaving the bone marrow.
Programmed cell death (apoptosis)
38
Takes place in the spleen
MATURE B CELL
39
remain in the spleen in order to respond quickly to any blood-borne pathogens they may come into contact with
Marginal Zone B cell
40
Lymph nodes and Other Secondary Lymphoid Organs (SLO)
MATURE B CELL
41
MATURE B CELL Distinguishing characteristic
Presence of IgM and IgD
42
same specificity for a particular antigen or group of antigens
Presence of IgM and IgD
43
is not required for B cell function but it may prolong the lifespan of mature B cells especially in peripheral blood
IgD
44
Naive B cells
Antigen-dependent phase
45
These B cells have a half-life of more than 6 weeks
Antigen-dependent phase
46
Primary Follicles of Peripheral Lymphoid tissues
Antigen-dependent activation
47
ACTIVATED B CELL Identifying Marker
CD25
48
found on both activated T and B cells
49
acts as a receptor for interleukin-2 (IL-2)
CD25
50
- a growth factor produced by T cells
interleukin-2 (IL-2)
51
Additional receptors that appear at this time are specific for other growth factors produced by T cells.
52
CD25
When B cells are activated in this manner, they transform into blasts that will give rise to both plasma cells and so-called (?).
memory cells
53
Not normally in the blood but are located in the germinal center of the peripheral lymphoid organs (PLO)
PLASMA CELLS
54
Spherical or ellipsoidal (10-20 um in size)
PLASMA CELLS
55
PLASMA CELLS Characterized by
Abundant cytoplasmic Immunoglobulin
Nucleus: eccentric or oval (heavily clamped chromatin-stains dark)
Abundant ER and well-defined golgi zone
56
are nondividing, and after several days of antibody production, they die without further proliferation
Plasma cells
57
Capable of responding to antigens with speed and intensity
MEMORY CELLS
58
Has longer life span
MEMORY CELLS
59
Represents progeny of antigen stimulated B cells
MEMORY CELLS
60
Similar in appearance with unstimulated B cells
MEMORY CELLS
61
They remain inactivated for months or years and ready to respond to antigen
MEMORY CELLS
62
Found in germinal layer
MEMORY CELLS
63
Sixty to 80 percent of circulating lymphocytes in the peripheral blood are (?), and these become differentiated in the (?).
T cells
thymus
64
– site of differentiation
Thymus
65
– Lymphocyte Precursors
Thymocytes
66
– Chemical messenger that dictates migration of thymocyte
Chemokines
67
Early Surface markers of Thymocytes:
CD44 and CD25
68
Maturation period:
3 weeks
69
T-cell maturation in the thymus.
70
T lymphocyte precursors (TP) enter the thymus at the cortico-medullary junction.
71
They migrate upward in the cortex and begin development of the T-cell receptor.
72
A small percent of precursors develops gamma-delta chains, while the majority develop alpha-beta chains and become double positive (DP) (both CD4 and CD8 are present).
73
Positive and negative selection take place through the CD3/T cell receptor for antigen.
74
If positively selected, the T cell becomes single-positive (SP); that is, either CD4_ or CD8_.
75
Further interaction with macrophages or dendritic cells takes place to weed out any T cells able to respond to self-antigen.
76
Surviving CD4_ and CD8_ cells exit the thymus to the peripheral cell
77
STAGES OF B CELL DIFFERENTIATION
78
STAGES OF T CELL DIFFERENTIATION
79
Lacks CD4 and CD8
Early thymocyte
80
Outer cortex
Active Proliferation
81
Influenced by Inteleukin-7
Active Proliferation
82
Rearrangement of the genes that code for the antigen receptor known as TCR begins at this stage CD3
Active Proliferation
83
TCR, CD3, a-chain and b-chain
Antigen receptors
84
1. DOUBLE NEGATIVE STAGE
85
Contains both CD4 and CD8 markers
DOUBLE POSITIVE STAGE
86
Expression of CD3ab Receptor Complex
DOUBLE POSITIVE STAGE
87
Double positive cells with functioning TCR
Positive selection
88
cells must recognize foreign antigen in association with class I or class II MHC molecules
Positive selection
89
Any thymocytes that are unable to recognize self-MHC antigens die without leaving the thymus.
Positive selection
90
This weeding out is important, because functioning T cells must be able to recognize foreign antigen along with MHC molecules.
Positive selection
91
Deletion of developing T cells
Negative Selection
92
takes place among the surviving double-positive T cells with functional TCR
Negative Selection
93
Strong reactions with self-peptides send a signal to delete the developing T cell by means of apoptosis, or programmed cell death.
Negative Selection
94
Most T cells that would be capable of an autoimmune response are eliminated
Negative Selection
95
This selection process is very rigorous, because only 1-3 % of the double-positive thymocytes in the cortex survive.
Negative Selection
96
Survivors of selection exhibit only one type of marker, either CD4 or CD8, and they migrate to the medulla.
MATURE T CELLS
97
MHC Class II protein
CD4+ T CELLS
98
Known as Helper or Inducer T cells
CD4+ T CELLS
99
TH1 – IFN-y and TNF-b
CD4+ T CELLS
100
TH2 – IL-4, IL-5, IL-10 and IL11
CD4+ T CELLS
101
MHC Class I Protein
CD8+ T CELLS
102
Cytotoxic T Cells
CD8+ T CELLS
103
Characterized by polyribosome filled cytoplasm
ANTIGEN ACTIVATION
104
Express receptors for IL-2
ANTIGEN ACTIVATION
105
ANTIGEN ACTIVATION
Activities:
Assisting B Cells in Antibody production
Kills tumor and other target cells
Rejects grafts
Stimulates hematopoiesis in the bone marrow
Stimulates delayed hypersensitivity reaction
106
A small percentage of lymphocytes do not express the markers of either T cells or B cells.
NATURAL KILLER CELLS
107
Larger than T and B Cells (15um in diameter)
NATURAL KILLER CELLS
108
They play an important role as a transitional cell bridging the innate and the acquired response to pathogens
NATURAL KILLER CELLS
109
Ability to mediate cytolytic reactions and kill target cells without prior exposure
NATURAL KILLER CELLS
110
Early defenders
NATURAL KILLER CELLS
111
lacks specificity
NATURAL KILLER CELLS
112
NATURAL KILLER CELLS
Surface Markers:
CD56 and CD16
113
They play an important role as a transitional cell bridging the innate and the acquired response
NATURAL KILLER CELLS
114
to pathogens
NATURAL KILLER CELLS
115
Gives time for T and B cells to activate
NATURAL KILLER CELLS
116
TWO SUBSETS OF NK CELLS
Increased CD56, decreased CD16
Decreased CD56, Increased CD16
117
Helpful to produce more cytokines and help support antibody production
Increased CD56, decreased CD16
118
Higher cytotoxic activity
Decreased CD56, Increased CD16
119
45-58
CD2
120
Thymocytes, T cells, NK cells
CD2
121
20-28
CD3
122
Thymocytes, T cells
CD3
123
Associated with T-cell antigen receptor; role in TCR signal transduction
CD3
124
55
CD4
125
Helper T cells, monocytes, macrophages
CD4
126
Coreceptor for MHC class II; receptor for HIV
CD4
127
58
CD5
128
Mature T cells, thymocytes, subset of B cells (B1)
CD5
129
Positive or negative modulation of T and B cell receptor signaling
CD5
130
60-76
CD8
131
Thymocyte subsets, cytotoxic T cell
CD8
132
Coreceptor for MHC class I
CD8
133
100
CD10
134
B and T cell precursors, bone marrow stromal cells
CD10
135
Protease; marker for pre-B CALLA
CD10
136
50-80
CD16
137
Macrophages, NK cells, neutrophils
CD16
138
Low affinity Fc receptor, mediates phagocytosis and ADCC
CD16
139
>120
CD19
140
B cells, follicular dendritic cell
CD19
141
Part of B cell coreceptor, signal transduction molecule that regulates B-cell development and activation
CD19
142
145
CD21
143
B cells, follicular dendritic cells, subset of immature thymocytes
CD21
144
Receptor for complement component C3d; part of B-cell coreceptor with CD19
CD21
145
45
CD23
146
B cells, monocytes, follicular dendritic cell
CD23
147
Regulation of IgE synthesis; triggers release of IL-1, IL-6, and GM-CSF from monocytes
CD23
148
55
CD25
149
Activated T, B cells, monocytes
CD25
150
Receptor for IL-2
CD25
151
85
CD44
152
Most leukocytes
CD44
153
Adhesion molecule mediating homing to peripheral lymphoid organs
CD44
154
180
CD25R
155
Different forms on all hematopoietic cells
CD25R
156
Essential in T and B cell antigen-stimulated activation
CD25R
157
175-220
CD56
158
NK cells, subsets of T cells
CD56
CD94
159
Not known
CD56
160
70
CD94
161
Subunit of NKG2-A complex involved in inhibition of NK cell cytotoxicity
CD94
162
CD94
