Lecture 15 - Differentiation and Functions of CD8+ T cells Flashcards

1
Q

The activation of B cells is initiated by what?

A

Specific recognition of Ags by the surface BCRs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What stimulates the proliferation and differentiation of specific B cell clone?

A

Ags and other stimuli, including T helper cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Progeny of the B cell clone may differentiate into what?

A
  1. Plasma cells that produce IgM or
  2. Other Ig isotypes e.g IgG
  3. May undergo affinity maturation
  4. May persist as memory cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Mature Ag-responsive B cells develop from what?

A

Bone marrow precursors in the absence of Ag

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Humoral immune responses are initiated by what?

A

The recognition of Ags by specific BCR on B lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

On naive B cells, Ag binds to what?

A

IgM and IgD and activates these cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

The activation of B cells results in what?

A

Their proliferation, leading to clonal expansion, followed by differentiation, culminating in the generation of Ab-secreting plasma cells and memory B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

A single B cells may give rise to how may cells per week?

A

5000 Ab-secreting cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

At the peak of humoral immune response, about how many Abs molecules are produced every day?

A

10^12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Some activated B cells begin to produce Abs other than IgM and IgD. This process is called what?

A

Heavy chain isotype (class) switching

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

As humoral immune response develops, activated B cells that produce Abs that bind to Ags with increasing affinity progressively do what?

A

Dominate the response, a process called affinity maturation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What determines the humoral immune response?

A

The type and amount of Abs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Humoral immune response can be what?

A

Either primary or secondary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Responses are divided on what?

A

T-dependent and T-independent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Ab responses to protein Ags require participation of what?

A

Of CD4+ Helper T lymphocytes

Therefore, proteins are classified as T-Dependent Ags

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

A specialized type of helper T cell facilitates the formation of germinal centers. What type of T cell is it?

A

Follicular helper T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are germinal centers?

A

Structures generated in secondary lymphoid organs where several steps of T-dependent humoral immune responses occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

In T-dependent responses, activated B cells differentiate into what?

A

Ab-secreting plasma cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Plasma cells migrate from GCs in the peripheral lymphoid organs to where?

A

The bone marrow where they may live for many years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

The long-lived plasma B cells do what?

A

Continuously secrete Abs that provide immediate protection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Ab responses to multivalent non-protein Ags with repeating epitopes, such as polysaccharides, some lipids, and nucleic acids, do not require what?

A

Ag-specific helper T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Multivalent Ags are called what?

A

T-independent Ags

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

T-independent responses are elicited by what?

A

Engagement of BCR and may be potentiated by the signals froom other receptors on the B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

B cells activated by protein Ags may differentiate into what?

A

memory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Memory B cells survive in a resting state without secreting Abs for many years, but they mount rapid responses on what?

A

Subsequent encounters with the Ags

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Isotype switching and affinity maturation are typically seen in what?

A

Humoral immune responses to protein Ags

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

T cell-dependent signals drive what?

A

Isotype switching and affinity maturation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Primary and secondary Ab responses to protein Ags differ in what?

A

Qualitatively and quantitatively

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

In primary immune responses, What happens to naive B cells?

A

Stimulated by Ag, become activated, and differentiate into Ab-secreting cells that produce Abs specific for the eliciting Ag

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

In secondary immune responses, what occurs with B cells?

A

The same Ag stimulates memory B cells, leading to the production of greater quantities of specific Abs than are produced in the primary response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What response develops more rapidly?

A

The secondary-larger amounts of Abs are produced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Heavy chain isotype switching and affinity maturation are increased in what response?

A

Secondary responses (multiple) to protein Ags

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Follicular B cells respond to what?

A

Protein Ags and thus initiate T-dependent Ab responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

T-independent responses to multivalent Ags are mediated mainly by what?

A

Marginal zone B cells in the spleen and B-1 cells in mucosal sites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

True or False

The functional distinctions between B cells subsets are not absolute?

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Follicular B cells respond to protein Ags and thus initiate what response?

A

T-dependent Ab responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Follicular B cells, protein antigen, isotype-switched, high-affinity; long-lived plasma cells
T-independent or T-dependent?

A

T-dependent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Marginal zone B cells, polysaccharides, lipids, etc. mainly IgM, short-lived plasma cells.
T-independent or T-dependent?

A

T-Independent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

B-1 Cells, multivalent, mainly IgM, short-lived plasma cells

T-independent or T-dependent?

A

T-independent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Antibody isotype is usually IgM>IgG

Primary or secondary response?

A

Primary

41
Q

Relative increases in IgG, and under certain situation, in IgA or IgE?
Primary or secondary response?

A

Secondary

42
Q

Response induced by all immunogens

Primary or secondary response?

A

Primary

43
Q

Response induced by mainly protein antigens

Primary or secondary response?

A

Secondary

44
Q

To initiate Ab responses, Ags have to be captured and transported where?

A

To the B cell areas of lymphoid organs

45
Q

Most mature naive B lymphocytes are what type of cells?

A

Follicular B cells which are also called recirculating B cells

46
Q

Follicular B cells constantly recirculate between what areas?

A

Recirculate in the blood and migrate from one secondary lympoid organ (spleen, lymph nodes, mucosal lymphoid tissues)

47
Q

In secondary lymphoid tissues, follicular B cells migrate into what zone?

A

The B cell zones called follicles

48
Q

What is the movement of follicular B cells guided by?

A

Chemokine CXCL13 secreted by follicular DCs

49
Q

What is the major stromal cell type in the follicle?

A

Follicular DCs

50
Q

Proteins are classified as what?

A

T-dependent Ags

51
Q

True or false?

Ag may be delivered to naive B cells in lymphoid organs in different forms and by multiple routes

A

True

52
Q

Most Ags from tissue sites are transported to lymph nodes by what vessels?

A

Afferent lymphatic vessels that drain into the subscapsular sinus of the LNs

53
Q

What Ags may reach the B cell zone of the follicle and interact DIRECTLY with specific B cells?

A

Soluble Ags (generally smaller than 70 kD)

54
Q

What are captured by subscapsular sinus macrophages which deliver Ags to follicles?

A

Microbes and Ag-Ab complexes

55
Q

What may be captured by resident DCs and transported into follicles, where they can activate B cells?

A

Many large Ags

56
Q

Follicular DCs can present Ags in what complexes to follicular B cells?

A

They express CR2 complement receptors and create complexes with the receptor

57
Q

In the spleen, Ags in immune complexes may bind to what on marginal zone B cells?

A

CR2 complement receptors

58
Q

What is the state of maturation of T lymphocytes in the bone?

A

pre-T cell

59
Q

What is the state of maturation of T lymphocytes in the thymus?

A

Selection of T cells with appropriately rearranged receptors for antigen

60
Q

That is the state of maturation of T lymphocytes in the LN?

A
  1. naive T cell
  2. Encounter with antigen-bearing DC leads to activation and functional polarisation to effector or memory T cell
  3. Memory T cell
61
Q

What is the state of maturation of T lymphocytes in the peripheral tissue?

A

T cells that carry out effector functions

62
Q

What can transfer the immune complex-containing Ags to follicular B cells?

A

Marginal zone B cells

63
Q

Blood-born pathogens may be captures by what cells in the blood and transported to the spleen where they may be delivered to marginal zone B cells?

A

Plasmacytoid dendritic cells

64
Q

What antigens can be captured by Mo in the marginal zone of the splenic lymphoid follicles and displayed or transferred to B cells in this area?

A

Polysaccharide

65
Q

The antigen that is presented to B cells is generally in what form?

A

Intact, native conformation and is not processed APCs

66
Q

How are small Ags delivered to B cells in follicles?

A

Through afferent lymphatics and via conduits

67
Q

How are larger Ags delivered to follicular B cells?

A

By subcapsular sinus Mo or by DCs in the medulla

68
Q

Follicular B cell survival depends on signals from the BCR as well as inputs received from what?

A

Cytokine called BAFF

69
Q

What is BAFF mainly produced by in lymphoid follicles and in the bone marrow?

A

Myeloid cells

70
Q

BAFF provides maturation and survival signals through what?

A

baff RECEPTOR

71
Q

What makes up the Ag receptor complex of mature B cells?

A

Membrane Ig molecules, Igα and Igβ proteins

72
Q

The initiates the process of B cell activation?

A

BCR initiates

73
Q

When the BCR initiates the process of B cell activation, what happens at the same time to the bound Ag?

A

The BCR internalizes the bound Ag into endosomal vesicles

74
Q

If the Ag is a protein, how is it processed in a B cell?

A

It is presented on Class II MHC on the B cell surface for recognition by T helper cells

75
Q

B cell activation is facilitated by what coreceptor on B cells?

A

CR2/CD21

76
Q

Activation of B cells through the BCR may be enhanced by complement-coated Ags that can ligate what?

A

Both the BCR and the CR2

77
Q

Simultaneous PAMPs recognition and TLRs signaling may contribute to what?

A

B cell activation

78
Q

Ag-induced cross-linking of the BCRs induces several cellular responses including what?

A
  1. production of proteins that promote survival and proliferation
  2. expression costimulators and cytokine receptors that promot interactions with and responsiveness to helper T cells
  3. migration of the cells towards T cells as a result of the expression of CCR7
79
Q

The activated T cells and B cells migrate towards one another and interact causing what?

A

B cell proliferation and differentiation

80
Q

B-T interaction in extrafollicular sites leads to what?

A

Isotype switching and short-lived plasma cell generation

81
Q

Activation of T cells by B cells results in the induction of what cells?

A

follicular helper T cells

82
Q

The late events of the immune defense that occur in the germinal centers include:

A
  1. somatic mutation and affinity maturation
  2. isotype switching
  3. generation of memory B cells and long-lived plasma cells
83
Q

what happens in responses to hapten-carrier conjugates?

A
The hapten (the B cell epitope) is recognized by a specific B cell
The conjugate is endocytosed, the carrier protein is processed int he B cell
Peptides from the carrier (the T cell epitopes) are presented to the helper T cell
84
Q

The germinal center is within the follicle and includes a dark and light zones. What do the zones contain?

A

Dark zone contains proliferating B cells stained with an anti-Ki67 Ab - red which detects cycling cells
The light zone contains follicular DCs stained with an anti-CD23 Ab (green)

85
Q

Activated B cells migrate into the follicle and proliferate, forming the dark zone of the germinal center. What do these B cells undero?

A

Extensive isotype switching and somatic hypermutation of Ig V genes

86
Q

B cells migrate into the light zone, where they encounter what?

A

follicular DCs displaying Ag and Tfh cells

87
Q

B cells with the highest affinity Ig receptors are selected to do what?

A

Survive, and they differentiate into Ab-secreting cells and memory B cells

88
Q

Ab-secreting cells leave and reside in what?

A

In the bone marrow as long-lived plasma cells

89
Q

What do memory B cells enter?

A

The recirculating lymphocyte pool?

90
Q

Within 4 to 7 days after Ag exposure, activated Ag-specific B cells induce what?

A

Some previously activated T cells to differentiate into Tfh cells

91
Q

Tfh cells are drawn into lymphoid follicles by what?

A

CXCL13

92
Q

Tfh cells play critical roles in ___ formation and function

A

GC

93
Q

Tfh cells express what 4 things?

A

ICOS, PD-1, IL-21, and Bcl-6

94
Q

Tfh cells have a unique phenotype that makes them distinct from what ?

A

Th1, Th2, Treg, and IL-17 subsets of effector T cells

95
Q

Tfh cells play several important roles in the activation and differentiation of B cells in the GC reaction that involves what on B cells

A

ICOSL, CD40L, IL-21R on B cells

96
Q

The generation of Tfh cells requires sequential activation of T cells first by what?

A

First B DCs and then by activated B cells.

The Tfh cells migrate to GCs, where they activate B cells

97
Q

What is secreted by Tfh cells and it is required for GC development and generation of plasma cells?

A

IL-21

98
Q

Tfh cells secrete what that controls isotype switching?

A

IFN-γ or IL-4