Question 1

T cell development in the thymus shares some similarities to a pipeline. As new progenitor cells enter the thymus, the most mature thymocytes are pushed out of the thymus to enter the circulation by a passive process.

Accepted Answer

A) True 
 B)False

Question 2

In different mammalian species, the ratio of B cells expressing $\kappa$ versus $\lambda$ light chain-containing antibodies is about 65%:35%. In other species, such as mice, this ratio is vastly different, at 95%:5%. If a routine blood test performed on an individual revealed that their $\lambda$-expressing versus $\lambda$-expressing B cells were seen at a ratio of 95%:5%, this would likely indicate that the individual had:

Accepted Answer

A)  An increased number of functional V$\kappa$ gene segments compared to the average human in the population 
B)  A defect in allelic exclusion of antibody light chain genes 
C)  A defect in isotypic exclusion of antibody light chains 
D)  A lymphoproliferative disorder 
E)  A genetic defect in one of their two $\lambda$ light chain alleles

Question 3

B cell development in the bone marrow is an inherently wasteful process. Nearly half of the pro-B cells produced will die without progressing on to the next stage of B cell development. This massive loss of pro-B cells is due to:

Accepted Answer

A)  The failure of many pro-B cells to up-regulate Pax5 and become committed to the B cell lineage. 
B)  The inability of many pro-B cells to proceed with rearranging a VH to their rearranged DJH sequence. 
C)  Large insertions of untemplated nucleotides into the rearranged gene by TdT. 
D)  Detrimental DJH rearrangements on both alleles of the immunoglobulin heavy chain locus. 
E)  The failure of the pro-B cell to make a complete immunoglobulin heavy chain protein.

Question 4

An infant is admitted to the hospital with a history of recurrent and persistent bacterial infections. His physician suspects he has an immunodeficiency disease, and obtains a sample of the patient's peripheral blood. The white blood cells are analyzed by antibody staining followed by flow cytometry, and the results are shown in Figure. To determine the origin of the peripheral blood cell defect, a bone marrow biopsy is taken from the patient and compared to a healthy control, as shown in Figure. To obtain additional information, bone marrow cells are treated with a chemical that permeabilizes the cell membrane, allowing antibodies to enter the cells and bind to their target antigens within the cells, a technique known as ‘intracellular staining’. The results of this analysis are shown in Figure . a) What are populations 1, 2, and 3 in Figure? b) In the analysis of cell surface expression (non-permeabilized bone marrow cells), what are the IgM^lo Igκ⁺λ^neg cells as indicated by the arrow in Figure? c) What is the most likely defect causing the patient's immunodeficiency? The results shown above indicate a specific defect in B cell development. To help identify the defective or missing protein in the patient's developing B cells, bone marrow cells are isolated and protein lysates are prepared for immunoblotting. A series of antibodies are tested and the results are shown in Figure. d) Given the results from the immunoblotting experiments, what is the most likely candidate molecule (or type of molecule) responsible for the patient's immunodeficiency disease?

Accepted Answer

The answer of  An infant is admitted to the...

Question 5

While many cell types in the thymus are able to induce negative selection of developing self-reactive thymocytes, bone marrow-derived antigen-presenting cells, such as macrophages and dendritic cells, appear to be the most important for this process. One likely reason for the prominent role of bone marrow-derived antigen-presenting cells in inducing negative selection of developing thymocytes is:

Accepted Answer

A)  Bone marrow-derived antigen-presenting cells are the most abundant stromal cells in the thymus. 
B)  Bone marrow-derived antigen-presenting cells are very good at inducing mature T cell activation. 
C)  Bone marrow-derived antigen-presenting cells are highly phagocytic and have specialized mechanisms for presenting peptides on both MHC class I and class II. 
D)  Bone marrow-derived antigen-presenting cells are concentrated in the thymic medulla where negative selection is most prominent. 
E)  Bone marrow-derived antigen-presenting cells are hematopoietic in origin, so share the same genetic make-up as the developing thymocytes.

Question 6

One feature of $\gamma$:$\delta$ T cells that identifies them as innate, rather than adaptive, lymphocytes is their ability to produce effector cytokines within hours of initial activation.

Accepted Answer

A) True 
 B)False

Question 7

A wild-type mouse that is heterozygous for two immunoglobulin heavy chain alleles (IgH^a/b) generates the population of B cells shown on the left of Figure . A mouse strain, also IgH^a/b, carries an inactivating mutation in the VpreB gene. In addition to producing fewer mature B cells than the wild-type mice, the VpreB-deficient mice generate B cells as shown on the right. What is the explanation of the difference seen between the wild-type and the VpreB-mutant B cells?

Accepted Answer

The answer of A wild-type mouse that is heterozygous for...

Question 8

A key step in the development of B cells is the expression of the RAG-1 and RAG-2 recombinase proteins. The up-regulation of RAG-1 and RAG-2 in early pro-B cells is induced by:

Accepted Answer

A)  The cytokine IL-7, which is made by bone marrow stromal cells 
B)  The chemokine CXCL12, which is made by bone marrow stromal cells 
C)  The B cell-specific transcription factors E2A and EBF 
D)  Signaling through the Igα subunit of the B-cell receptor complex 
E)  Signaling through the FLT3 receptor tyrosine kinase binding to membrane-bound FLT3

Question 9

The mouse thymus normally contains about 1–2 x 108 thymocytes, the vast majority of which are CD4+CD8+ (double-positive) cells. When thymocytes from mice with a gene deficiency in the TCR$\alpha$ locus are compared with those from TCR$\beta$-deficient mice, a striking difference between the two different knockout lines is observed, as shown in Figure in a simplified version of flow cytometry data. The numbers of thymocytes in each thymus is indicated below the plots. -Which region of the thymus organ would show a dearth of developing thymocytes in the TCR$\alpha$^-/- thymus? Which region in the TCR$\beta$^-/- thymus?

Accepted Answer

The answer of The mouse thymus normally contains about 1–2...

Question 10

Proteins found in the circulation travel throughout the body, including the thymus. One example is serum albumin. Developing T cells with T-cell receptors specific for peptides of human serum albumin bound to MHC class II molecules would likely be:

Accepted Answer

A)  Positively selected and would mature into CD4 T cells 
B)  Positively selected and would mature into CD8 T cells 
C)  Negatively selected in the thymus and deleted from the mature repertoire 
D)  Targeted for peripheral mechanisms of self-tolerance after emigrating from the thymus 
E)  Excluded from the T cell zones of the spleen after emigrating from the thymus

Question 11

Marginal zone B cells are thought to represent a lineage of cells important in rapid responses to blood-borne antigens. What are the two characteristics of these cells that indicate this function?

Accepted Answer

The answer of Marginal zone B cells are thought to...

Question 12

Current evidence indicates that >95% of the CD4⁺CD8⁺ double-positive thymocytes generated will die in the thymus, and will never develop into mature CD4 or CD8 T cells. While a small proportion of these double-positive thymocytes may fail to produce a functional $\alpha$:$\beta$ T-cell receptor, the majority of them do express a T-cell receptor complex on their surface. For any given double-positive thymocyte undergoing cell death in the thymus, what are the two possible explanations for its failure to mature?

Accepted Answer

The answer of Current evidence indicates that >95% of the...

Question 13

Progenitor cells that migrate from the bone marrow to the thymus are not yet committed to the T cell lineage. T cell lineage commitment occurs as a result of signals received by the progenitor cell from thymic epithelial cells.

Accepted Answer

A) True 
 B)False

Question 14

Experiments performed with T-cell receptor transgenic mice identified the fate of developing thymocytes that failed positive selection. Based on these findings, examination of thymocytes in MHC class I-MHC class II-deficient mice (lacking all MHC class I and class II expression in the thymus) would show:

Accepted Answer

A)  A 100-fold decrease in total thymocytes numbers 
B)  A block in T cell development at the CD4-CD8- double-negative stage 
C)  Normal numbers and subsets of thymocytes and peripheral T cells 
D)  Normal numbers of thymocytes, but no peripheral T cells 
E)  A block in T cell development at the CD4+CD8+ double-positive stage

Question 15

The thymic cortex has a substantial population of macrophages in addition to the developing T cells (i.e., thymocytes). These macrophages are extremely useful in:

Accepted Answer

A)  Eliminating bacterial infections in the thymus 
B)  Producing cytokines that promote T cell maturation 
C)  Engulfing apoptotic thymocytes 
D)  Maintaining the structural integrity of the thymic organ 
E)  Inducing inflammatory signals to increase blood flow to the thymus

Question 16

Unlike $\alpha$:$\beta$ T cells, $\gamma$:$\delta$  T cells are considered to be components of the innate immune system. One feature of $\gamma$:$\delta$  T cells that leads to their classification as innate cells is:

Accepted Answer

A)  That they migrate from the thymus directly to barrier surfaces such as mucosa and epithelia 
B)  Their ability to produce pro-inflammatory cytokines 
C)  That their T-cell receptors are germline encoded rather than a product of VD-J recombination 
D)  Their rapid turnover in the tissue, with an average survival time of 3-4 days 
E)  Their ability to make growth factors that act on epithelial cells rather than other hematopoietic cells

Question 17

Autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are characterized by high levels of circulating autoreactive antibodies in the patient's circulation. An analysis of developing B cells in the bone marrow of these individuals might reveal that in some cases:

Accepted Answer

A)  Developing B cells become anergic in response to strong B-cell receptor cross-linking by multivalent self-antigens. 
B)  Developing B cells are excluded from the B-cell follicles in the bone marrow and undergo rapid cell death. 
C)  sIgM-positive developing B cells show premature down-regulation of RAG recombinase proteins prior to the onset of receptor editing. 
D)  Hyperactive B-cell receptor signaling leads to rapid turnover of self-reactive developing B cells. 
E)  Developing B cells have defects in allelic exclusion and express two different B-cell receptors on their surface.

Exam 8: Development and Survival of Lymphocytes

T cell development in the thymus shares some similarities to a pipeline. As new progenitor cells enter the thymus, the most mature thymocytes are pushed out of the thymus to enter the circulation by a passive process.

B cell development in the bone marrow is an inherently wasteful process. Nearly half of the pro-B cells produced will die without progressing on to the next stage of B cell development. This massive loss of pro-B cells is due to:

One feature of $\gamma$ : $\delta$ T cells that identifies them as innate, rather than adaptive, lymphocytes is their ability to produce effector cytokines within hours of initial activation.

A key step in the development of B cells is the expression of the RAG-1 and RAG-2 recombinase proteins. The up-regulation of RAG-1 and RAG-2 in early pro-B cells is induced by:

Proteins found in the circulation travel throughout the body, including the thymus. One example is serum albumin. Developing T cells with T-cell receptors specific for peptides of human serum albumin bound to MHC class II molecules would likely be:

Marginal zone B cells are thought to represent a lineage of cells important in rapid responses to blood-borne antigens. What are the two characteristics of these cells that indicate this function?

Progenitor cells that migrate from the bone marrow to the thymus are not yet committed to the T cell lineage. T cell lineage commitment occurs as a result of signals received by the progenitor cell from thymic epithelial cells.

The thymic cortex has a substantial population of macrophages in addition to the developing T cells (i.e., thymocytes) . These macrophages are extremely useful in:

Unlike $\alpha$ : $\beta$ T cells, $\gamma$ : $\delta$ T cells are considered to be components of the innate immune system. One feature of $\gamma$ : $\delta$ T cells that leads to their classification as innate cells is:

Exam 8: Development and Survival of Lymphocytes

T cell development in the thymus shares some similarities to a pipeline. As new progenitor cells enter the thymus, the most mature thymocytes are pushed out of the thymus to enter the circulation by a passive process.

B cell development in the bone marrow is an inherently wasteful process. Nearly half of the pro-B cells produced will die without progressing on to the next stage of B cell development. This massive loss of pro-B cells is due to:

One feature of γ\gammaγ : δ\deltaδ T cells that identifies them as innate, rather than adaptive, lymphocytes is their ability to produce effector cytokines within hours of initial activation.

A key step in the development of B cells is the expression of the RAG-1 and RAG-2 recombinase proteins. The up-regulation of RAG-1 and RAG-2 in early pro-B cells is induced by:

Proteins found in the circulation travel throughout the body, including the thymus. One example is serum albumin. Developing T cells with T-cell receptors specific for peptides of human serum albumin bound to MHC class II molecules would likely be:

Marginal zone B cells are thought to represent a lineage of cells important in rapid responses to blood-borne antigens. What are the two characteristics of these cells that indicate this function?

Progenitor cells that migrate from the bone marrow to the thymus are not yet committed to the T cell lineage. T cell lineage commitment occurs as a result of signals received by the progenitor cell from thymic epithelial cells.

The thymic cortex has a substantial population of macrophages in addition to the developing T cells (i.e., thymocytes) . These macrophages are extremely useful in:

Unlike α\alphaα : β\betaβ T cells, γ\gammaγ : δ\deltaδ T cells are considered to be components of the innate immune system. One feature of γ\gammaγ : δ\deltaδ T cells that leads to their classification as innate cells is:

One feature of $\gamma$ : $\delta$ T cells that identifies them as innate, rather than adaptive, lymphocytes is their ability to produce effector cytokines within hours of initial activation.

Unlike $\alpha$ : $\beta$ T cells, $\gamma$ : $\delta$ T cells are considered to be components of the innate immune system. One feature of $\gamma$ : $\delta$ T cells that leads to their classification as innate cells is: