Lecture 14 (Exam 2)

Question 1

Mature Ag-responsive B cells develop from ______ ______ precursors in the absence of Ag.

Answer 1

Bone marrow

Question 2

Humoral immune responses are initiated by the recognition of Ags by specific _____ on B lymphocytes.

Answer 2

BCR

Question 3

Ag activates mature NAIVE B cells by binding to membrane _____ and _____ on these cells.

Answer 3

IgM

IgD

Question 4

A single B cell may give rise to as many as _____ Ab-secreting cells per week.

Answer 4

5,000

Question 5

At the peak of humoral immune response, about 10(12) Abs are produced every (WEEK/DAY).

Answer 5

Day

Question 6

The activation of B cells is initiated by specific recognition of ____ by the surface BCRs.

Answer 6

Ags

Question 7

Ags and other stimuli, including _______ cells, stimulate the proliferation and differentiation of the specific B cell clone.

Answer 7

T helper

Question 8

The progeny of the B cell clone may differentiate into plasma cells that produce –

1) _____
2) Other Ig isotypes (i.e., IgG)
3) Undergo ______ ______
4) ______ cells

Answer 8

IgM
Affinity maturation
Memory

Question 9

Primary and secondary Ab responses to _______ Ags differ qualitatively and quantitatively.

Answer 9

Protein

Question 10

In a (PRIMARY/SECONDARY) immune response, naive B cells are stimulated by Ag, become activated, and differentiate into Ab-secreting cells that produce Abs. _____ > _____ specific for the eliciting Ag.

Answer 10

Primary
IgM
IgG

Question 11

A (PRIMARY/SECONDARY) immune response is elicited when the same Ag stimulates _______ B cells, leading to production of Abs (_____ > ______).

Answer 11

Secondary
IgG
IgM

Question 12

Secondary response is characterized by –

– More ______ production of Abs than was produced in the primary response.

– ______ amounts of Abs produced as compared to the primary response.

– _______ _______ of the heavy chain.

– _______ _______ Ag-Ab binding.

Answer 12

Rapid
Larger
Isotype switching
Affinity maturation

Question 13

B cell responses are divided on _______ and _______.

Answer 13

T-dependent (TD)

T-independent (TI)

Question 14

Ab responses to multivalent non-protein Ags with repeating epitopes, such as polysaccharides, some lipids, and nucleic acids, do not require Ag-specific helper T lymphocytes. Multivalent Ags are called _______ Ags.

Answer 14

TI (T-independent)

Question 15

TI responses are elicited by engagement of _____ and may be potentiated by the signals from other receptors on the B cells.

Answer 15

BCR

Question 16

In contrast, Ab responses to protein Ags require participation (help) of CD4+ T helper lymphocytes. Therefore, proteins are classified as _______ Ags.

Answer 16

TD (T-dependent)

Question 17

A specialized type of helper T cell, called a ________ helper T cell, facilitates the formation of _______ ______ where activated B cells proliferate.

Answer 17

Follicular 
Germinal centers (GCs)

Question 18

Follicular B-2 cells respond to protein Ags and thus initiate _______ Ab responses.

Answer 18

T-dependent

Question 19

Marginal zone B cells respond to multivalent Ags and are ________.

Answer 19

T-independent

Question 20

B-1 cells in mucosal sites also respond to multivalent Ags and are ________.

Answer 20

T-independent

Question 21

The (B-1/B-2) B cells arise from the fetal liver by the eighth gestational week. These cells might represent a transitional type of lymphocyte that bridges the innate and adaptive immune systems. They are T-independent.

Answer 21

B-1

Question 22

The B-1 B cell repertoire is quite limited in comparison to that of _____ cells.

Answer 22

B-2

Question 23

B-1 B cell _____ are often directed against conserved microbial Ags.

Answer 23

Abs

Question 24

Conventional B cells, which are _____ B cells, are widely distributed throughout the body. These cells are continually replaced from the bone marrow throughout adult life and require interaction with T cells for their activation and proliferation (T-dependent).

Answer 24

B-2

Question 25

To initiate Ab responses, Ags have to be transported to the B cell areas of the _____ and _____.

Answer 25

LNs | Spleen

Question 26

Most mature naive B lymphocytes are ________ B cells which are also called recirculating B cells or _____ cells.

Answer 26

Follicular | B-2

Question 27

Follicular B cells constantly recirculate in the blood from one to another secondary lymphoid organ, which are...

Answer 27

Spleen Lymph nodes Mucosal lymphoid tissues

Question 28

In the secondary lymphoid organs, follicular B cells migrate into the B cell zones of these tissues called _______.

Answer 28

Follicles

Question 29

The ______ chemokine secreted by resident follicular DCs (FDCs are not DCs coming from tissues) guides the movement of B cells.

Answer 29

CXCL13

Question 30

CXCL13 attracts naive B cells into the _______.

Answer 30

Follicles

Question 31

The Ag that is presented to B cells is generally in its intact, native conformation and is not processed _____.

Answer 31

APCs

Question 32

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

Answer 32

True

Question 33

Most Ags from tissue sites are transported to lymph nodes by _______ _______ _______ that drain into the _________ ________ of the LNs.

Answer 33

Afferent lymphatic vessels | Subcapsular sinus

Question 34

_______ Ags (generally smaller than 70 kD) may reach the B cell zone of the follicle and interact directly with B cells.

Answer 34

Soluble

Question 35

_______ Ags may be captured by resident FDCs and transported into follicles, where they can activate B cells.

Answer 35

Large

Question 36

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

Answer 36

Macrophages

Question 37

FDCs play a central role in the (INNATE/ADAPTIVE) immune response.

Answer 37

Adaptive

Question 38

As a major stroll cell constituent of follicles, FDCs secrete _______ to organize the intra-follicular migration of B cells and T-FH cells (follicular T helper cells).

Answer 38

CXCL13

Question 39

FDCs have the unique capacity to retain immune Ag-Ab complexes on their surface for long periods (week to month). Ags retention by FDCs is mediated by ________, _____ or _____ complement receptors. These immune complexes play a key role during the germinal center reaction, as they provide the antigenic substrate that drives antibody _______ _______.

Answer 39

FcyRIIb (Fc receptors) CR1 CR2 (CD21) Affinity maturation

Question 40

FDCs do NOT express ________, and they do NOT phagocytose and process exogenous Ags for ________.

Answer 40

Class II MHC | Class II MHC

Question 41

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

Answer 41

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

Question 42

BAFF provides maturation and survivor signals through the _______ _______.

Answer 42

BAFF receptor

Question 43

BAFF is mainly produced by _______ cells in lymphoid follicles and in the bone marrow.

Answer 43

Myeloid

Question 44

The BCR signaling (1) initiates the process of B cell activation. At the same time, the BCR (2) internalizes the bound Ag into eadosomal vesicles. If the Ag is a _______, it is processed and presented (class II MHC) on the B cell surface for recognition by T helper cells.

Answer 44

Protein

Question 45

B cell activation is facilitated by the _____/_____ coreceptor on B cells. Activation of B cells through the BCR may be enhanced by complement-coated Ags that can ligate both the BCR and _____.

Answer 45

CR2/CD21 | CR2

Question 46

Simultaneous _______ recognition and TLRs signaling may contribute to B cell activation.

Answer 46

PAMPs

Question 47

Some non-microbial polysaccharides also activate complement, and this is one reason that such Ags are able to induce Ab responses without ______ help.

Answer 47

T cell

Question 48

Protein Ags recognized by membrane Ig are endocytose and processed, and peptide fragments are presented in association with ________ molecules.

Answer 48

Class II MHC

Question 49

_______ cells recognize MHC-peptide complexes on the B cells and then stimulate B cell responses.

Answer 49

Helper T

Question 50

In responses to _______-_______ conjugates, the _______ (the B cell epitope) is recognized by a specific B cell, the conjugate is endocytose, the carrier protein is processed in the B cell, and peptides from the carrier (the T cell epitopes) are presented to the helper T cell.

Answer 50

Hapten-carrier | Hapten

Question 51

When helper T cells are activated by recognizing Ags presented by B cells, they initiate the expression of ______.

Answer 51

CD40L

Question 52

CD40L binds to ______ on B cells and stimulates B cell proliferation and differentiation.

Answer 52

CD40

Question 53

_________ produced by the helper T cells also contribute to B cell responses.

Answer 53

Cytokines

Question 54

Immune responses are initiated by the recognition of _____ by B cells and CD4+ T cells.

Answer 54

Ags

Question 55

The activated lymphocytes migrate toward one another and interact causing B cell _________ and ________.

Answer 55

Proliferation | Differentiation

Question 56

B-T interaction leads to minimal isotype switching and generation of short-lived plasma cells mainly producing _____ (some may produce _____ having relatively low affinity).

Answer 56

IgM | IgG

Question 57

B cells migrate into the ________ ________ and undergo (a) somatic mutation, (b) affinity maturation, (c) isotype switching, generation memory B cell and long-lived plasma cells producing either IgG, IgA, IgM, or IgE.

Answer 57

Germinal centers

Question 58

The _______ is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body such as GI tract, oral passage, nasopharyngeal tract, lung, etc.

Answer 58

MALT (Mucosa-associated lymphoid tissue)

Question 59

The generation of _____ cells requires sequential activation of T cells, first by DCs and then by activated B cells. The ______ cells migrate into germinal centers, where they activate B cells.

Answer 59

T-FH (Follicular helper T cell) | T-FH

Question 60

_______ is a receptor for CXCL13, and mediates migration in the B cell zone.

Answer 60

CXCR5

Question 61

______ is secreted by T-FH cells and it is required for GC development and generation of plasma cells.

Answer 61

IL-21

Question 62

T-FH cells secrete cytokine(s) ______, ______, or ______ which control Ab isotype switching.

Answer 62

IFN-y IL-4 TGF-B

Question 63

Within 4 to 7 days after Ag exposure, activated Ag-specific B cells induce some previously activated T cells to differentiate into _______ cells.

Answer 63

T-FH

Question 64

______ cells have a unique phenotype that makes them distinct from the Th1, Th2, Treg, and Th17 subsets of effector T cells.

Answer 64

T-FH

Question 65

T-FH cells are drawn into lymphoid follicles by _______ and play a critical role in GC formation and function.

Answer 65

CXCL13

Question 66

T-FH cells express ______, ______, the cytokine ______, and the transcription repressor ______.

Answer 66

ICOS (Inducible costimulator) PD-1 (Programmed death-1) IL-21 Bcl-6

Question 67

T-FH plays several roles in the activation and differentiation of B cells in the GC reactions that involves ______, ______, and _____ on B cells.

Answer 67

ICOSL CD40L IL-21R

Question 68

Cytokine ______ is important for the generation of B cell responses in germinal centers resulting in development of B cells, isotype switching, affinity maturation, and antibody production.

Answer 68

IL-21

Question 69

The GC can be divided into three zones, which are...

Answer 69

Dark zone Light zone Mantle zone

Question 70

Activated B cells migrate into the follicle and proliferate, forming the _____ zone of the germinal center. These B cells undergo extensive isotype switching and somatic hypermutation of Ig V genes.

Answer 70

Dark

Question 71

B cells migrate into the ______ zone, where they encounter follicular DCs displaying Ags and T-FH cells.

Answer 71

Light

Question 72

B cells with the highest affinity Ig receptors receive "tonic signal" to survive, and they proceed for the positive/negative selection or ______ editing.

Answer 72

BCR

Question 73

Positively selected B cells differentiate into Ab-secreting cells and _______ B cells.

Answer 73

Memory

Question 74

The Ab-secreting cells leave the GC and reside in the bone marrow as long-lived _______ cells, and the memory B cells enter the recirculating lymphocyte pool.

Answer 74

Plasma

Question 75

The ______ zone surrounds a GC and contains tightly packed small B cells of the primary follicles, pushed aside by GCs.

Answer 75

Mantle

Question 76

Ag- induced cross-linking of the BCRs and signaling induces several cellular responses including -- 1) Production of proteins that promote survival and proliferation, expression costimulators and cytokine receptors that promote interactions with and responsiveness to helper T cells. 2) The expression of ______ induces migration of the cells toward the T cell zone.

Answer 76

CCR7

Question 77

A _______ is an activated B cell that is enlarged and proliferating in the GC of a secondary lymphoid follicle.

Answer 77

Centroblast

Question 78

The most distinctive cell types in the marginal zone are...

Answer 78

Marginal-zone (MZ) macrophages | Marginal B cells

Question 79

Lymphocytes and DCs can enter the _____ _____ from the marginal sinus by passing through a layer of sinus-lining cells that form a barrier between the marginal zone and the _____ _____.

Answer 79

White pulp | White pulp

Question 80

A framework of reticular _______ forms the basis of the marginal zone.

Answer 80

Fibroblasts

Question 81

Splenic MZ ______ serve as sentinels at the interface between the circulation and lymphoid tissue.

Answer 81

B cells

Question 82

MZ B cells rapidly respond to blood-borne viruses and encapsulated bacteria by adopting "________" defensive strategies that blur the conventional boundaries of innate and adaptive immunity.

Answer 82

Crossover

Question 83

MZ B cells mount rapid Ab responses to both T cell-dependent and T cell-independent _____.

Answer 83

Ags

Question 84

MZ B cells may produce _____ and class-switched ____ and ____ Abs in response to commensal Ags that physiologically translocate from the intestinal mucosa to the general circulation in the absence of infection.

Answer 84

IgM IgG IgA

Question 85

This innate-like humoral response of MZ B cells may generate a ready-to-use pre-immune antibody repertoire that provides a rapid systemic line of defense not only against pathogens, but also against commensal bacteria that breach the _______ barrier.

Answer 85

Mucosal

Question 86

MZ B cells have a lower activation threshold than follicular B cells, which permits the rapid initiation of IgM production and of IgG- and IgA-inducing class-switch recombination (CSR) in the absence of CD40-dependent help from _______ cells.

Answer 86

T-FH

Question 87

This T cell-independent pathway requires dual BCR and TLR engagement by conserved microbial Ags together with co-stimulatory signals from DCs and macrophages via various ________.

Answer 87

Cytokines

Question 88

The Ags presented to MZ B cells are generally in native conformation which are not processed ______.

Answer 88

APCs

Question 89

Ags in immune complexes may bind to _____ complement receptors on MZ B cells. MZ B cells can transfer the immune complex-containing Ags to follicular DCs.

Answer 89

CR2

Question 90

Blood-borne pathogens may be captured by __________ DCs in the blood and transported to the spleen, where they may be delivered to MZ B cells.

Answer 90

Plasmacytoid (pDCs)

Question 91

In the spleen, polysaccharide Ags can be captured by MZ ________ and displayed or transferred to MZ B cells in this area.

Answer 91

Macrophages

Question 92

After entering the splenic MZ via the marginal sinus, TI Ags are captured by MZ _________. Alternatively, TI antigens are captured by ______ and ______ in the circulation.

Answer 92

Macrophages DCs Neutrophils

Question 93

Ag-presenting MZ macrohages stimulates MZ B cells via the ______ and ______. The stimulation delivers signals that induce class-switch recombination and Ab production after ligating ______ and a proliferation-inducing ligand (______), which are released by APCs in response to microbial TLR ligands.

Answer 93

BCR TLRs BAFF APRIL

Question 94

APCs, including red pulp DCs and macrophages, also secrete _____, ______, and type I _______ (IFNs). These cytokines cooperate with BAFF and APRIL to promote the differentiation and survival of IgM-secreting or class-switched IgG-secreting plasma cells.

Answer 94

IL-6 IL-10 Interferons