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Immunology Exam III > Handout 12 part 1: Differentiation and Functions of CD8+ T cells > Flashcards

Handout 12 part 1: Differentiation and Functions of CD8+ T cells Flashcards

1
Q

How is the activation of B cells initiated?

A

by specific recognition of Ags by the surface BCRs

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2
Q

How does a B cell proliferate–what stimulation helps it proliferate and differentiate?

A

Ags and other stimuli like T helper cells stimulate the proliferation and differentiation of the specific B cell clone

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3
Q

After a B cell proliferates, what types of cells can it become?

A

Can differentiate into a plasma cell that produces IgM (secretes Ab)
cell that expresses IgG or other isotype (isotype switching)
High affinity Ig expressing B cell (affinity maturation)
Memory cells

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4
Q

Sequence of events in humoral immune respose

A

Recognition of Ag by Naive IgM+ or IgD+ B cell–>Activated B cell–>Proliferation which can become one of the following:
Plasma cell–>Ab secretion
IgG expressing B cell–>Isotype switching
High affinity Ig expressing B cell–>Affinity maturation
High affinity Ig expressing B cell–>Memory B cell

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5
Q

Where do mature Ag-responsive B cells develop? Do they need an Ag?

A

Develop from bone marrow; no they develop from bone marrow in the absence of Ag

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6
Q

How are humoral immune responses initiated?

A

by the recognition of Ags by specific BCR on B lymphocytes

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7
Q

How are B cells activated?

A

Ag binds to membrane IgM and IgD on mature, naive B cells and activates these cells

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8
Q

How do B cells proliferate into plasma cells and memory cells?

A

Activation leads to their proliferation which leads to clonal expansion, followed by differentiation which generates Ab-secreting plasma cells and memory B cells

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9
Q

How many Ab-secreting cells does one single B cell give rise to?

A

5000 Ab-secreting cells per week

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10
Q

How many Abs molecules are produced every day when humoral immune response is at its peak?

A

10^12 Ab molecules

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11
Q

What is heavy chain isotype (class) switching?

A

When activated B cells produce Abs other than IgM and IgD

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12
Q

What is affinity maturation?

A

when an activated B cell produces Abs that bind to Ags with increasing affinity which progressively dominate the developing humoral immune response

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13
Q

What two things determines whether a response is primary or secondary in humoral immunity?

A

The type and amount of Abs produced

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14
Q

Humoral immune response can be T dependent or T independent. Ab responses to what kind of Ags are T dependent?

A

Ab response to protein Ags require help of CD4+ helper T lymphocytes so proteins are T-dependent Ags

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15
Q

What kind of helper T cell facilitates the formation of germinal centers?

A

specialized type of helper T cell, called follicular helper T cell

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16
Q

Where are germinal centers generated? What occurs in this area?

A

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

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17
Q

What must activated B cells differentiate into in T-dependent responses?

A

activated B cells must differentiate into Ab-secreting plasma cells

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18
Q

From where and to where do plasma cells migrate? What do they secrete?

A

Plasma cells migrate from germinal centers in the peripheral lymphoid organs to the bone marrow where they live for many years. They continuously secrete Abs that provide immediate protection

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19
Q

What kind of Ags are T-independent Ags?

A

Multivalent Ags are T independent and do not require Ag specific helper T lymphocyte. They are non-protein and have repeating epitopes like:
polysaccharides,
some lipids and
nucleic acids

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20
Q

T-independent responses are elicited by engagement of ____ and may be potentiated by signals from ___ ____ on the B cell

A

BCR, other receptors

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21
Q

What kind of B cells differentiate into memory cells?

A

B cells activated by protein Ags

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22
Q

Are memory T (B??) cells always active?

A

No, they survive in a resting state without secreting Abs for many years but mount rapid responses on subsequent encounters with the Ags

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23
Q

What kind of Ags initiate isotype switching and affinity maturation?

A

typically seen in humoral immune responses to protein Ags

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24
Q

What drives isotype switching and affinity maturation?

A

T-cell dependent signals

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25
Q

Primary and secondary Ab responses to protein Ags differ both qualitatively and quantitatively. What are some major differences between primary and secondary immune responses?

A

Primary response: Naive B cells stimulated by Ag becomes activated and differentiate into Ab-secreting cells that produce Abs specific for the eliciting Ag

Secondary response: elicicited when the SAME Ag stimulates memory B cells leading to production of greater quantities of specific Abs than in primary response

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26
Q

What is different in terms of the quantity and quality of response between primary and secondary response?

A

secondary response develops more rapidly and larger amounts of Abs are produced than in primary response

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27
Q

Does primary or secondary response have increased heavy chain isotype switching and affinity maturation to protein Ags?

A

Secondary response

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28
Q

Primary vs. secondary response graph

A

Primary: First infection (slower response): Naive B cell–>Activated B cell–>short lived plasma cells in bone marrow–>low-level Ab production

Secondary: Repeat infection (rapid response, high levels of Ab produced): Memory B cell–>Plasma cell–>Long-lived plasma cells in bone marrow–> Memory B cell

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29
Q

Primary vs. Secondary response:
Peak response: Smaller/larger
Ab affinity: high/low affinity
Induced by: what kind of Ag?

A

Primary response:
Peak response smaller
Ab affinity: lower average affinity, more variable
Induced by all immunogens

Secondary response:
Peak response larger
Ab affinity: higher average affinity (affinity maturation)
Induced by: mainly protein Ags

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30
Q

What kind of B cells respond to protein Ags and are therefore T-dependent Ab responses? Which kind of B cells are T-independent B cells?

A

Follicular B cells respond to protein Ags (T-dependent)
Marginal zone B cells in spleen and B-1 cells in mucosal sites mediate responses to multivalent Ags and are T-independent

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31
Q

Where are follicular B cells found?

A

In the spleen and in other lymphoid organs

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32
Q

Sequence of events for T-dependent B cell response

A

Follicular B cells in spleen/other lymphoid organ–>protein Ag and helper T cell–> T dependent isotype-switched, high affinity Abs; long lived plasma cells

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33
Q

Sequence of events for T-independent B cell response

A

Marginal zone B cells in spleen/lymphoid organ OR B-1 cell in mucosal tissues/peritoneal cavity–>polysaccharides, lipids, etc–>T independent, mainly IgM; short lived plasma cells

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34
Q

To initiate Ab responses, what must happen to the Ag?

A

It must be captured and transported to the B cell areas of lymphoid organs

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35
Q

Most mature naive B lymphocytes are what kinds of cells? What is another name for these cells?

A

They are follicular B cells which are also called reciruculating B cells

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36
Q

Where do Follicular B cells circulate? Where do they migrate from?

A

Follicular B cells constantly recirculate in the blood and migrate from one secondary lymphoid organ (spleen, lymphnodes, mucosal lymphoid tissues)

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37
Q

In secondary lymphoid tissues, follicular B cells migrate into the ___ ___ ___ of these tissues called ___

A

B cell zones

follicles

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38
Q

What chemokine guides the movement of follicular B cells into lymphoid follicles (B cell zone)?

A

chemokine CDCL13 secreted by follicular DCs which is the major stromal cell type in the follicle

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39
Q

CXCL13 attracts ___ _ ___ into follicles

A

naive B cells

40
Q

Ag may be delivered to naive B cells in lymphoid organs in different forms and via multiple routes. How are most Ags from tissue transported into lymphoid organs?

A

Ags transported to lymph nodes via afferent lymphatic vessels that drain into subcapsular sinus of the LNs

41
Q

Soluble Ags, Microbes and Ag-Ab complexes and large Ags are delivered to B cell zone of follicle in different ways. What are these differences?

A

Soluble Ags (smaller than 70 kD) reaches B cell zone of follicle and interact directly with specific B cells

Microbes and Ag-Ab complexes are captured by subcapsular sinus macrophages which deliver Ags to follicles

Large Ags are captured by resident DCs and transported into follicles where they can activate B cells

42
Q

What receptor do follicular DCs express that plays a role in Ag presentation?

A

Follicular DCs express CR2 complement receptor so they can present Ags to follicular B cells

43
Q

What do the complement receptor CR2 bind to?

A

In the spleen, Ags in immune complexes bind to the CR2 complement receptor

44
Q

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

A

Marginal zone B cells

45
Q

How are blood-borne pathogens delivered to marginal zone B cells?

A

They are captured by plasmacytoid dendritic cells (pDCs) in the blood and transported to the spleen where they may be delivered to marginal zone B cells

46
Q

How are polysaccharide Ags captured?

A

They are captured by macrophages in the marginal zone of splenic lymphoid follicles and displayed or transferred to B cells in this area

47
Q

Is the Ag presented to B cells processed by the APC?

A

No, the Ag presented to B cells is generally in its intact, native conformation and is not processed by APC

48
Q
  1. Small Ags are delivered to B cells in the follicles through ___ ___ and via ____
  2. Larger Ags are delivered by ___ ___ ___ or by __ in the ___
A
  1. afferent lymphatics, conduits

2. subcapsular sinus macrophages, DCs in medulla

49
Q

Follicular B cell survival depends on signals from the BCR as well as on inputs received from cytokine called ___

A

BAFF (B cell-activating factor of the TNF family)

50
Q

What cells produce BAFF? Where?

A

BAFF is mainly produced by myeloid cells in lymphoid follicles and in bone marrow

51
Q

What is the function of the BAFF?

A

It provides maturation and survival signals through the BAFF receptor

52
Q

How is the Ag-specific B lymphocyte activation initiated?

A

by the binding of Ag to membrane Ig molecules which together with the associated Iga and IgB proteins make up the Ag receptor complex of mature B cells

53
Q

What initiates the process of B cell activation? What else occurs at the same time?

A

BCR

BCR internalizes the bound Ag into endosomal vesicles

54
Q

If the Ag is a protein, how it it processed and presented?

A

It is processed and presented within class II MHC on the B cell surface for recognition by T helper cells

55
Q

B cell activation is facilitated by the ___/___ coreceptor on B cells

A

CR2/CD21

56
Q

Simultaneous ____ recognition and ___ signaling may contribute to B cell activation

A

PAMP, TLRs

57
Q

How is the activation of B cells through BCRs enhanced?

A

by complement-coated Ags that can ligate both the BCR and complement receptor 2 (CR2)

58
Q

How are non-microbial polysaccaride Ags able to induce Ab response without T cell help?

A

by activating complement

59
Q

What are the cellular responses induced by Ag-induced cross-linking of BCRs?

A
  1. production of proteins that promote survival and proliferation, expression of costimulators and cytokine receptors that promote interactions with and responsiveness to helper T cells
  2. Migration of the cells toward T cells due to expression of CCR7
60
Q

Ag binding to and cross-linking of memrane Ig–>Changes in activated B cells–>Functional consequences:

Naive B lymphocyte recognizes Ag–>Expression of proteins that promote survival and cell cycling–>Result?

A

Increased B cell survival, proliferation

61
Q

Ag binding to and cross-linking of memrane Ig–>Changes in activated B cells–>Functional consequences:

Naive B lymphocyte recognizes Ag–>Ag presentation, increased B7 expression–>Result?

A

Interaction with helper T cells

62
Q

Ag binding to and cross-linking of memrane Ig–>Changes in activated B cells–>Functional consequences:

Naive B lymphocyte recoginizes Ag–>increased expression of cytokine receptors–>Result?

A

Responsiveness to cytokines

63
Q

Ag binding to and cross-linking of memrane Ig–>Changes in activated B cells–>Functional consequences:

Naive B lymphocyte recognizes Ag–>increased expression of CCR7–>Result?

A

Micration from follicle to T cell areas

64
Q

In T cell-dependent responses, immune responses are initiated by the recognition of Ags by B cells and _____

Then, the activated B cells and T helper cells migrate towards each other and interact causing what?

A

CD4+ T cells

proliferation and differentiation

65
Q

B-T cell interaction in extrafollicular sites leads to ___ ___ and __ __ ___ __ ___

A

isotype switching

short-lived plasma cell generation

66
Q

Activation of T cells by B cells results in the induction of ______ ___ ___

A

follicular helper T-cells

67
Q

The late events in T cell dependent responses occur in germinal centers. What happens in the germinal center?

A

somatic mutation and affinity maturation, isotype switching, generation of memory B cell and long-lived plasma cells

68
Q

How are B cell Ags presented to T cells?

A

Protein Ags recognized by membrane Ig are endocytosed and processed, and peptide fragments are presented within class II MHC molecules. Then, helper T cells recognize MHC-peptide complexes on B cells and stimulate B cell response

69
Q

What happens after the hapten (B cell eptiope) is recongized by a specific Bcell?

A

The hapten carrier conjugate is endocytosed, carrier protein is processed in B cell, peptides from carrier (T cell epitopes) are presented to helper T cell

70
Q

Sequence of events for B cell Ag presentation to T cells

A

Receptor (conformational epitope-specific Bcell receptor) mediated endocytosis of Ag–>Ag processing and presentation within class II MHC peptide complex–> T cell recognition of Ag

71
Q

What ligand do helper T cells that are activated by Ags presented by B cells express?

A

CD40L

72
Q

What does CD40L bind to?

A

CD40L (expressed by helper T cells) binds to CD40 on B cells and stimulates B cell proliferation and differentiation

73
Q

Aside from the CD40-CD40L binding, cytokines produced by what kind of cell contributes to B cell responses?

A

Cytokines produced by helper T cell

74
Q

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A

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75
Q

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A

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76
Q

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A

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77
Q

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A

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78
Q

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A

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79
Q

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A

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80
Q

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A

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81
Q

slide 26

A

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82
Q

The germinal center is within the ___ and includes a __ and __ zone

A

follicle

dark, light

83
Q

The dark zone contains what kinds of cells? The light zone contains what kind of cells?

A

Dark zones contains proliferating B cells (can stain with anti-Ki67 Ab thats red to detect cycling cells)

Light zone contains follicular DCs which can be stained with an anti-CD23 Ab

84
Q

How is the dark zone formed?

A

Activated B cells migrate into the follicle and proliferate, forming the dark zone

85
Q

Which B cells undergo extensive isotype switching and somatic hypermutation of Ig V genes?

A

Activated and proliferated B cells in the DARK ZONE

86
Q

What happens after the B cells migrate from the dark zones into the light zones?

A

They encouter follicular DCs displaying Ag and T follicular helper cells

87
Q

How is it determined which B cells survive and differentiate?

A

B cells with the highest affinity Ig receptors are selected to survive and they differentiate into Ab secreting cells and memory B cells

88
Q

Where do the Ab-secreting cells then go after being in the germinal center?

A

They leave and reside in the bone marrow as long-lived plasma cells, and the memory B cells enter the recirculating lymphocyte pool

89
Q

Germinal center sequence of events:

A

Activation of B cells by T helper cell and migration into germinal center–>B cell proliferation__>somatic mutation and affinity maturation; isotype switching–>Exit of high-affinity Ab-secreting cells and memory B cells

90
Q

When and how do T cells differentiate into Follicular helper T cells?

A

Within 4-7 days of Ag exposure, activated Ag-specific B cells induce some previously activated T cells to differentiate into Follicular T helper cells

91
Q

What cytokine plays a critical role in drawing Tfh cells into lymphoid follicles and in germinal center formation and function?

A

CXCL13

92
Q

What costimulators, cytokines and transcription factors do follicular helper T cells express?

A

ICOS (inducible costimulator)
PD-1 (programmed death-1)
cytokine IL-21
transcription factor Bcl-6

93
Q

Follicular Helper T cells are distinct from which other T cells?

A

Distinct from other T cells like Th1, Th2, Treg, and Th17 subsets of effector T cells

94
Q

Tfh cells play important roles in the ____ and ___ of B cells in the germinal center. What cytokines and receptors/ligands does it use?

A

activation, differentiation

uses: ICOSL, CD40L, IL-21R on B cells

95
Q

The generation of follicular helper T cells requires the sequential activation of T cell–first by ___, and then by ___ ___. The Tfh cells migrate to ___ where they activate B cells

A

DC, activated B cells

Germinal centers

96
Q

What cytokines do Tfh cells secrete? What do each of these cytokines do?

A

secretes IL-21 neededfor GC development and generation of plasma cells
IFN-gamma or IL-4 which controls isotype switching

Immunology Exam III (5 decks)

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